CORD-19-Sentences  

CORD-19:b1d31bf64148c3dabdd5b8a288b78c0c6d3a7cea JSONTXT 8 Projects

Annnotations TAB TSV DIC JSON TextAE-old TextAE

Id Subject Object Predicate Lexical cue
TextSentencer_T1 0-40 Sentence denotes Curating the innate immunity interactome
TextSentencer_T1 0-40 Sentence denotes Curating the innate immunity interactome
TextSentencer_T2 42-50 Sentence denotes Abstract
TextSentencer_T2 42-50 Sentence denotes Abstract
TextSentencer_T3 51-62 Sentence denotes Background:
TextSentencer_T3 51-62 Sentence denotes Background:
TextSentencer_T4 63-214 Sentence denotes The innate immune response is the first line of defence against invading pathogens and is regulated by complex signalling and transcriptional networks.
TextSentencer_T4 63-214 Sentence denotes The innate immune response is the first line of defence against invading pathogens and is regulated by complex signalling and transcriptional networks.
TextSentencer_T5 215-358 Sentence denotes Systems biology approaches promise to shed new light on the regulation of innate immunity through the analysis and modelling of these networks.
TextSentencer_T5 215-358 Sentence denotes Systems biology approaches promise to shed new light on the regulation of innate immunity through the analysis and modelling of these networks.
TextSentencer_T6 359-517 Sentence denotes A key initial step in this process is the contextual cataloguing of the components of this system and the molecular interactions that comprise these networks.
TextSentencer_T6 359-517 Sentence denotes A key initial step in this process is the contextual cataloguing of the components of this system and the molecular interactions that comprise these networks.
TextSentencer_T7 518-667 Sentence denotes InnateDB (http://www.innatedb.com) is a molecular interaction and pathway database developed to facilitate systems-level analyses of innate immunity.
TextSentencer_T7 518-667 Sentence denotes InnateDB (http://www.innatedb.com) is a molecular interaction and pathway database developed to facilitate systems-level analyses of innate immunity.
TextSentencer_T8 668-676 Sentence denotes Results:
TextSentencer_T8 668-676 Sentence denotes Results:
TextSentencer_T9 677-995 Sentence denotes Here, we describe the InnateDB curation project, which is manually annotating the human and mouse innate immunity interactome in rich contextual detail, and present our novel curation software system, which has been developed to ensure interactions are curated in a highly accurate and data-standards compliant manner.
TextSentencer_T9 677-995 Sentence denotes Here, we describe the InnateDB curation project, which is manually annotating the human and mouse innate immunity interactome in rich contextual detail, and present our novel curation software system, which has been developed to ensure interactions are curated in a highly accurate and data-standards compliant manner.
TextSentencer_T10 996-1102 Sentence denotes To date, over 13,000 interactions (protein, DNA and RNA) have been curated from the biomedical literature.
TextSentencer_T10 996-1102 Sentence denotes To date, over 13,000 interactions (protein, DNA and RNA) have been curated from the biomedical literature.
TextSentencer_T11 1103-1344 Sentence denotes Here, we present data, illustrating how InnateDB curation of the innate immunity interactome has greatly enhanced network and pathway annotation available for systems-level analysis and discuss the challenges that face such curation efforts.
TextSentencer_T11 1103-1344 Sentence denotes Here, we present data, illustrating how InnateDB curation of the innate immunity interactome has greatly enhanced network and pathway annotation available for systems-level analysis and discuss the challenges that face such curation efforts.
TextSentencer_T12 1345-1565 Sentence denotes Significantly, we provide several lines of evidence that analysis of the innate immunity interactome has the potential to identify novel signalling, transcriptional and post-transcriptional regulators of innate immunity.
TextSentencer_T12 1345-1565 Sentence denotes Significantly, we provide several lines of evidence that analysis of the innate immunity interactome has the potential to identify novel signalling, transcriptional and post-transcriptional regulators of innate immunity.
TextSentencer_T13 1566-1870 Sentence denotes Additionally, these analyses also provide insight into the cross-talk between innate immunity pathways and other biological processes, such as adaptive immunity, cancer and diabetes, and intriguingly, suggests links to other pathways, which as yet, have not been implicated in the innate immune response.
TextSentencer_T13 1566-1870 Sentence denotes Additionally, these analyses also provide insight into the cross-talk between innate immunity pathways and other biological processes, such as adaptive immunity, cancer and diabetes, and intriguingly, suggests links to other pathways, which as yet, have not been implicated in the innate immune response.
TextSentencer_T14 1871-2005 Sentence denotes In summary, curation of the InnateDB interactome provides a wealth of information to enable systems-level analysis of innate immunity.
TextSentencer_T14 1871-2005 Sentence denotes In summary, curation of the InnateDB interactome provides a wealth of information to enable systems-level analysis of innate immunity.
TextSentencer_T15 2007-2218 Sentence denotes The immune system is traditionally divided into two different branches -the adaptive immune system, the arm of the immune system that mounts a specific response to foreign antigens, and the innate immune system.
TextSentencer_T15 2007-2218 Sentence denotes The immune system is traditionally divided into two different branches -the adaptive immune system, the arm of the immune system that mounts a specific response to foreign antigens, and the innate immune system.
TextSentencer_T16 2219-2444 Sentence denotes The importance of the innate immune response is now well recognised as the first, and perhaps even the most critical, line of defence against invading pathogens and there has been an explosion of interest in investigating it.
TextSentencer_T16 2219-2444 Sentence denotes The importance of the innate immune response is now well recognised as the first, and perhaps even the most critical, line of defence against invading pathogens and there has been an explosion of interest in investigating it.
TextSentencer_T17 2445-2662 Sentence denotes Innate immunity is fast-acting by comparison to the adaptive response, which can take several days to respond, and furthermore, innate immunity instructs, regulates and shapes the subsequent adaptive response [1, 2] .
TextSentencer_T17 2445-2662 Sentence denotes Innate immunity is fast-acting by comparison to the adaptive response, which can take several days to respond, and furthermore, innate immunity instructs, regulates and shapes the subsequent adaptive response [1, 2] .
TextSentencer_T18 2663-2863 Sentence denotes Despite the lack of antigen specificity present in adaptive immunity, components of the innate immune system can still distinguish between a broad range of pathogens and mount an appropriate response.
TextSentencer_T18 2663-2863 Sentence denotes Despite the lack of antigen specificity present in adaptive immunity, components of the innate immune system can still distinguish between a broad range of pathogens and mount an appropriate response.
TextSentencer_T19 2864-3241 Sentence denotes Receptors of the innate immune response, known as pathogen recognition receptors (PRRs), recognise specific molecular motifs or signatures (often called pathogen-associated molecular patterns or PAMPs) expressed by invading pathogens [3] , including lipopolysaccharide (LPS), peptidoglycan, lipoteichoic acid, lipopeptides, flagellin, bacterial CpG DNA and viral nucleic acids.
TextSentencer_T19 2864-3241 Sentence denotes Receptors of the innate immune response, known as pathogen recognition receptors (PRRs), recognise specific molecular motifs or signatures (often called pathogen-associated molecular patterns or PAMPs) expressed by invading pathogens [3] , including lipopolysaccharide (LPS), peptidoglycan, lipoteichoic acid, lipopeptides, flagellin, bacterial CpG DNA and viral nucleic acids.
TextSentencer_T20 3242-3553 Sentence denotes The best-studied family of PRRs in humans are the Toll-like receptors (TLRs) [4] , however, the importance of other PRRs including the nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) [5, 6] , and the retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) is becoming evident [7, 8] .
TextSentencer_T20 3242-3553 Sentence denotes The best-studied family of PRRs in humans are the Toll-like receptors (TLRs) [4] , however, the importance of other PRRs including the nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) [5, 6] , and the retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) is becoming evident [7, 8] .
TextSentencer_T21 3554-3886 Sentence denotes NLRC4, for example, has recently been shown to be involved in the recognition of components of the bacterial type III secretion system, enabling the discrimination between pathogenic and non-pathogenic bacteria [9] ; while the recognition of microbiota peptidoglycan by Nod1 has been shown to enhance systemic innate immunity [10] .
TextSentencer_T21 3554-3886 Sentence denotes NLRC4, for example, has recently been shown to be involved in the recognition of components of the bacterial type III secretion system, enabling the discrimination between pathogenic and non-pathogenic bacteria [9] ; while the recognition of microbiota peptidoglycan by Nod1 has been shown to enhance systemic innate immunity [10] .
TextSentencer_T22 3887-4006 Sentence denotes The RIG-I pathway has been shown to have a critical role in the response to a range of viral pathogens [11] [12] [13] .
TextSentencer_T22 3887-4006 Sentence denotes The RIG-I pathway has been shown to have a critical role in the response to a range of viral pathogens [11] [12] [13] .
TextSentencer_T23 4007-4247 Sentence denotes Recently, we have reviewed the complexity of the innate immune response and have argued that innate immunity does not involve simple linear pathways, but rather complex networks of molecular interactions and transcriptional responses [14] .
TextSentencer_T23 4007-4247 Sentence denotes Recently, we have reviewed the complexity of the innate immune response and have argued that innate immunity does not involve simple linear pathways, but rather complex networks of molecular interactions and transcriptional responses [14] .
TextSentencer_T24 4248-4505 Sentence denotes Over the last three years, we have developed InnateDB (http://www.innatedb. com), a database of the molecular interactions and pathways involved in innate immunity and an analysis platform enabling systems-level analysis of the innate immune response [15] .
TextSentencer_T24 4248-4505 Sentence denotes Over the last three years, we have developed InnateDB (http://www.innatedb. com), a database of the molecular interactions and pathways involved in innate immunity and an analysis platform enabling systems-level analysis of the innate immune response [15] .
TextSentencer_T25 4506-4653 Sentence denotes A key component of the Inna-teDB project is the contextual manual curation of innate immunity interactions, pathways and their component molecules.
TextSentencer_T25 4506-4653 Sentence denotes A key component of the Inna-teDB project is the contextual manual curation of innate immunity interactions, pathways and their component molecules.
TextSentencer_T26 4654-4757 Sentence denotes In our original article on InnateDB, approximately 3,500 molecular interactions had been curated [15] .
TextSentencer_T26 4654-4757 Sentence denotes In our original article on InnateDB, approximately 3,500 molecular interactions had been curated [15] .
TextSentencer_T27 4758-4863 Sentence denotes Currently (July 2010), more than 13,000 interactions of relevance to innate immunity have been annotated.
TextSentencer_T27 4758-4863 Sentence denotes Currently (July 2010), more than 13,000 interactions of relevance to innate immunity have been annotated.
TextSentencer_T28 4864-5188 Sentence denotes Given this significant progress, now is an appropriate time to review the InnateDB curation process and our novel customised software that enables curation in a data-standards and ontology compliant manner and to highlight some of the new insights that are being revealed through curation of the innate immunity interactome.
TextSentencer_T28 4864-5188 Sentence denotes Given this significant progress, now is an appropriate time to review the InnateDB curation process and our novel customised software that enables curation in a data-standards and ontology compliant manner and to highlight some of the new insights that are being revealed through curation of the innate immunity interactome.
TextSentencer_T29 5189-5413 Sentence denotes Systems biology approaches reflect the biological reality that complex cellular processes like the immune response are not regulated by straightforward linear pathways but by networks of complex molecular interactions [14] .
TextSentencer_T29 5189-5413 Sentence denotes Systems biology approaches reflect the biological reality that complex cellular processes like the immune response are not regulated by straightforward linear pathways but by networks of complex molecular interactions [14] .
TextSentencer_T30 5414-5583 Sentence denotes To undertake systems-level analyses of the innate immune response, one must first have a catalogue of the components of the system and how they interact with each other.
TextSentencer_T30 5414-5583 Sentence denotes To undertake systems-level analyses of the innate immune response, one must first have a catalogue of the components of the system and how they interact with each other.
TextSentencer_T31 5584-5749 Sentence denotes Generating such a catalogue is complicated by the fact that the interactome is a dynamic entity, in which the interactions that occur are dependent on their context.
TextSentencer_T31 5584-5749 Sentence denotes Generating such a catalogue is complicated by the fact that the interactome is a dynamic entity, in which the interactions that occur are dependent on their context.
TextSentencer_T32 5750-5940 Sentence denotes Such contextual considerations include the cell and/or tissue type, the environmental or experimental conditions including the presence of specific stimuli, the species, the time-point, etc.
TextSentencer_T32 5750-5940 Sentence denotes Such contextual considerations include the cell and/or tissue type, the environmental or experimental conditions including the presence of specific stimuli, the species, the time-point, etc.
TextSentencer_T33 5941-6094 Sentence denotes Additionally, the level of confidence that an interaction actually occurs (and has biological relevance) in vivo can be dependent on a number of factors.
TextSentencer_T33 5941-6094 Sentence denotes Additionally, the level of confidence that an interaction actually occurs (and has biological relevance) in vivo can be dependent on a number of factors.
TextSentencer_T34 6095-6358 Sentence denotes These include the interaction detection method, whether the interaction was detected in vitro or in vivo, on additional experimental approaches used to validate the interaction, and whether the interaction has been independently reported by other research groups.
TextSentencer_T34 6095-6358 Sentence denotes These include the interaction detection method, whether the interaction was detected in vitro or in vivo, on additional experimental approaches used to validate the interaction, and whether the interaction has been independently reported by other research groups.
TextSentencer_T35 6359-6546 Sentence denotes Several large-scale efforts to identify all possible molecular interactions that make up the interactome are well under way in several species [16] [17] [18] [19] , including human [20] .
TextSentencer_T35 6359-6546 Sentence denotes Several large-scale efforts to identify all possible molecular interactions that make up the interactome are well under way in several species [16] [17] [18] [19] , including human [20] .
TextSentencer_T36 6547-6634 Sentence denotes Although these efforts are enormously valuable, they are not without their limitations.
TextSentencer_T36 6547-6634 Sentence denotes Although these efforts are enormously valuable, they are not without their limitations.
TextSentencer_T37 6635-6845 Sentence denotes Many of these projects, for example, are focused on protein-protein interactions and rely heavily on yeast two-hybrid approaches, which can be associated with high false positive and false negative rates [21] .
TextSentencer_T37 6635-6845 Sentence denotes Many of these projects, for example, are focused on protein-protein interactions and rely heavily on yeast two-hybrid approaches, which can be associated with high false positive and false negative rates [21] .
TextSentencer_T38 6846-6999 Sentence denotes Furthermore, such approaches do not provide detailed contextual insight into which interactions occur under particular conditions or in which cell-types.
TextSentencer_T38 6846-6999 Sentence denotes Furthermore, such approaches do not provide detailed contextual insight into which interactions occur under particular conditions or in which cell-types.
TextSentencer_T39 7000-7115 Sentence denotes In addition to these large-scale efforts, a large number of interactions are reported in the biomedical literature.
TextSentencer_T39 7000-7115 Sentence denotes In addition to these large-scale efforts, a large number of interactions are reported in the biomedical literature.
TextSentencer_T40 7116-7303 Sentence denotes These usually involve relatively low-throughput investigations of interactions between a handful of molecules, but are nonetheless, a valuable source of data for defining the interactome.
TextSentencer_T40 7116-7303 Sentence denotes These usually involve relatively low-throughput investigations of interactions between a handful of molecules, but are nonetheless, a valuable source of data for defining the interactome.
TextSentencer_T41 7304-7421 Sentence denotes Although there may only be a few interactions reported in each publication, there are thousands of such publications.
TextSentencer_T41 7304-7421 Sentence denotes Although there may only be a few interactions reported in each publication, there are thousands of such publications.
TextSentencer_T42 7422-7603 Sentence denotes Critically, such publications frequently report rich contextual information on the interaction, and interactions are often validated using several different experimental approaches.
TextSentencer_T42 7422-7603 Sentence denotes Critically, such publications frequently report rich contextual information on the interaction, and interactions are often validated using several different experimental approaches.
TextSentencer_T43 7604-7699 Sentence denotes Thus, extracting annotation on such interactions from the literature can be extremely valuable.
TextSentencer_T43 7604-7699 Sentence denotes Thus, extracting annotation on such interactions from the literature can be extremely valuable.
TextSentencer_T44 7700-8022 Sentence denotes Although literature mining approaches potentially provide a high-throughput, low cost approach to extracting information and annotation from the literature [22] , such approaches can be highly inaccurate, often rely on text in an abstract rather than the full-text, and do not substitute for curation by a trained curator.
TextSentencer_T44 7700-8022 Sentence denotes Although literature mining approaches potentially provide a high-throughput, low cost approach to extracting information and annotation from the literature [22] , such approaches can be highly inaccurate, often rely on text in an abstract rather than the full-text, and do not substitute for curation by a trained curator.
TextSentencer_T45 8023-8376 Sentence denotes Several databases have now been established as repositories for molecular interaction data including the Molecular Interaction database (MINT) [23] ; the IntAct database [24] ; the Database of Interacting Proteins (DIP) [25] ; the General Repository for Interaction Datasets (BioGRID) [26] and the Biomolecular Interaction Network Database (BIND) [27] .
TextSentencer_T45 8023-8376 Sentence denotes Several databases have now been established as repositories for molecular interaction data including the Molecular Interaction database (MINT) [23] ; the IntAct database [24] ; the Database of Interacting Proteins (DIP) [25] ; the General Repository for Interaction Datasets (BioGRID) [26] and the Biomolecular Interaction Network Database (BIND) [27] .
TextSentencer_T46 8377-8574 Sentence denotes Each of these has similar quality and data standards requirements to InnateDB and have been integrated into InnateDB to provide a comprehensive framework of the entire human and mouse interactomes.
TextSentencer_T46 8377-8574 Sentence denotes Each of these has similar quality and data standards requirements to InnateDB and have been integrated into InnateDB to provide a comprehensive framework of the entire human and mouse interactomes.
TextSentencer_T47 8575-8816 Sentence denotes IntAct, DIP, MINT and BioGRID have active literature curation efforts and are members of the International Molecular Exchange Consortium (IMEx) (http://www.imexconsortium.org/), which aims to synchronise curation efforts to avoid redundancy.
TextSentencer_T47 8575-8816 Sentence denotes IntAct, DIP, MINT and BioGRID have active literature curation efforts and are members of the International Molecular Exchange Consortium (IMEx) (http://www.imexconsortium.org/), which aims to synchronise curation efforts to avoid redundancy.
TextSentencer_T48 8817-8917 Sentence denotes InnateDB is now an observer member of this consortium and is working towards full active membership.
TextSentencer_T48 8817-8917 Sentence denotes InnateDB is now an observer member of this consortium and is working towards full active membership.
TextSentencer_T49 8918-9123 Sentence denotes The sheer scale of the task involved in curating interactions from the literature, however, means that even a large consortium, such as IMEx, must focus its efforts to particular journals and publications.
TextSentencer_T49 8918-9123 Sentence denotes The sheer scale of the task involved in curating interactions from the literature, however, means that even a large consortium, such as IMEx, must focus its efforts to particular journals and publications.
TextSentencer_T50 9124-9247 Sentence denotes Indeed, several of the partner databases concentrate their curation efforts on papers published in fewer than ten journals.
TextSentencer_T50 9124-9247 Sentence denotes Indeed, several of the partner databases concentrate their curation efforts on papers published in fewer than ten journals.
TextSentencer_T51 9248-9464 Sentence denotes Importantly from an immunology perspective, neither the journals that are routinely curated nor the databases themselves have a specific focus on the immune system, and in particular, not on the innate immune system.
TextSentencer_T51 9248-9464 Sentence denotes Importantly from an immunology perspective, neither the journals that are routinely curated nor the databases themselves have a specific focus on the immune system, and in particular, not on the innate immune system.
TextSentencer_T52 9465-9608 Sentence denotes Therefore, the majority of interactions of relevance to innate immunity are not annotated by these efforts (see Figure 1 for evidence thereof).
TextSentencer_T52 9465-9608 Sentence denotes Therefore, the majority of interactions of relevance to innate immunity are not annotated by these efforts (see Figure 1 for evidence thereof).
TextSentencer_T53 9609-9843 Sentence denotes Additionally, investigation of the pathways and molecular interactions involved in innate immunity is a fast-moving field, with an explosion of publications in recent years and new interactions being reported on an almost daily basis.
TextSentencer_T53 9609-9843 Sentence denotes Additionally, investigation of the pathways and molecular interactions involved in innate immunity is a fast-moving field, with an explosion of publications in recent years and new interactions being reported on an almost daily basis.
TextSentencer_T54 9844-10052 Sentence denotes To address these issues and to undertake a curation process that has a specific interest in the innate immune system, the InnateDB project has had a full-time curation team employed for more than three years.
TextSentencer_T54 9844-10052 Sentence denotes To address these issues and to undertake a curation process that has a specific interest in the innate immune system, the InnateDB project has had a full-time curation team employed for more than three years.
TextSentencer_T55 10053-10282 Sentence denotes As of February 15th 2010, there were 11,786 InnateDB-curated molecular interactions in InnateDB (>3,000 published articles reviewed) and an additional 117,066 (mostly non-overlapping) interactions integrated from other databases.
TextSentencer_T55 10053-10282 Sentence denotes As of February 15th 2010, there were 11,786 InnateDB-curated molecular interactions in InnateDB (>3,000 published articles reviewed) and an additional 117,066 (mostly non-overlapping) interactions integrated from other databases.
TextSentencer_T56 10283-10527 Sentence denotes This integration of molecular interactions from other databases provides broad coverage of the entire human and mouse interactomes -the innate immunity relevant portion of this interactome is then enriched through curation by the InnateDB team.
TextSentencer_T56 10283-10527 Sentence denotes This integration of molecular interactions from other databases provides broad coverage of the entire human and mouse interactomes -the innate immunity relevant portion of this interactome is then enriched through curation by the InnateDB team.
TextSentencer_T57 10528-10780 Sentence denotes Currently, InnateDB only curates interactions involving human and mouse molecules, with the majority of curated interactions (72% or 8,569 interactions) involving human molecules (although there has been no specific focus on human as opposed to mouse).
TextSentencer_T57 10528-10780 Sentence denotes Currently, InnateDB only curates interactions involving human and mouse molecules, with the majority of curated interactions (72% or 8,569 interactions) involving human molecules (although there has been no specific focus on human as opposed to mouse).
TextSentencer_T58 10781-10875 Sentence denotes Additionally, there are 1,005 hybrid interactions involving both human and mouse participants.
TextSentencer_T58 10781-10875 Sentence denotes Additionally, there are 1,005 hybrid interactions involving both human and mouse participants.
TextSentencer_T59 10876-11098 Sentence denotes Curated interactions are primarily protein-protein interactions (9,244 interactions), however, there are also almost 2,500 protein-DNA interactions and a small, but important, number of RNA interactions (mainly microRNAs).
TextSentencer_T59 10876-11098 Sentence denotes Curated interactions are primarily protein-protein interactions (9,244 interactions), however, there are also almost 2,500 protein-DNA interactions and a small, but important, number of RNA interactions (mainly microRNAs).
TextSentencer_T60 11099-11177 Sentence denotes MicroRNAs are now being recognised as key regulators of innate immunity [28] .
TextSentencer_T60 11099-11177 Sentence denotes MicroRNAs are now being recognised as key regulators of innate immunity [28] .
TextSentencer_T61 11178-11318 Sentence denotes The 11,500+ curated interactions can be grouped into 7,985 non-redundant interactions (based on the same participants and interaction type).
TextSentencer_T61 11178-11318 Sentence denotes The 11,500+ curated interactions can be grouped into 7,985 non-redundant interactions (based on the same participants and interaction type).
TextSentencer_T62 11319-11475 Sentence denotes Of these, 6,882 (86%) were curated only by InnateDB, while 1,103 also have been curated by one of the other databases integrated into InnateDB ( Figure 1 ).
TextSentencer_T62 11319-11475 Sentence denotes Of these, 6,882 (86%) were curated only by InnateDB, while 1,103 also have been curated by one of the other databases integrated into InnateDB ( Figure 1 ).
TextSentencer_T63 11476-11639 Sentence denotes As illustrated, without the InnateDB curation efforts there would be a significant paucity in the innate immunity interactome available for systems-level analyses.
TextSentencer_T63 11476-11639 Sentence denotes As illustrated, without the InnateDB curation efforts there would be a significant paucity in the innate immunity interactome available for systems-level analyses.
TextSentencer_T64 11640-11784 Sentence denotes InnateDB also enhances pathway-specific networks providing a more comprehensive picture of pathway signalling than traditional pathway diagrams.
TextSentencer_T64 11640-11784 Sentence denotes InnateDB also enhances pathway-specific networks providing a more comprehensive picture of pathway signalling than traditional pathway diagrams.
TextSentencer_T65 11785-11911 Sentence denotes Figure 2 illustrates this point for the RIG-I signalling pathway, a key pathway in the anti-viral innate immune response [7] .
TextSentencer_T65 11785-11911 Sentence denotes Figure 2 illustrates this point for the RIG-I signalling pathway, a key pathway in the anti-viral innate immune response [7] .
TextSentencer_T66 11912-12054 Sentence denotes The KEGG pathway database [29] depicts RIG-I signalling in a clear linear fashion that would be recognisable to most biologists ( Figure 2A ).
TextSentencer_T66 11912-12054 Sentence denotes The KEGG pathway database [29] depicts RIG-I signalling in a clear linear fashion that would be recognisable to most biologists ( Figure 2A ).
TextSentencer_T67 12055-12335 Sentence denotes If, however, we use Inna-teDB to construct a network of all the possible interactions between components of this pathway ( Figure 2B ), we can see that such pathway diagrams are a convenient simplification of the inter-connectivity and likely crosstalk between pathway components.
TextSentencer_T67 12055-12335 Sentence denotes If, however, we use Inna-teDB to construct a network of all the possible interactions between components of this pathway ( Figure 2B ), we can see that such pathway diagrams are a convenient simplification of the inter-connectivity and likely crosstalk between pathway components.
TextSentencer_T68 12336-12457 Sentence denotes Curated InnateDB information greatly enhances this network-orientated perspective of innate immunity signalling pathways.
TextSentencer_T68 12336-12457 Sentence denotes Curated InnateDB information greatly enhances this network-orientated perspective of innate immunity signalling pathways.
TextSentencer_T69 12458-12544 Sentence denotes Over half of the interactions illustrated (>200) have been curated solely by InnateDB.
TextSentencer_T69 12458-12544 Sentence denotes Over half of the interactions illustrated (>200) have been curated solely by InnateDB.
TextSentencer_T70 12545-12852 Sentence denotes Furthermore, if we expand upon this view ( Figure 2C ) and visualise all potential molecular interactions involving components of this pathway, one can clearly see the potential for Figure 1A which were curated only by InnateDB in comparison to the BIND, DIP, MINT, IntAct and BioGRID databases (i.e. >80%).
TextSentencer_T70 12545-12852 Sentence denotes Furthermore, if we expand upon this view ( Figure 2C ) and visualise all potential molecular interactions involving components of this pathway, one can clearly see the potential for Figure 1A which were curated only by InnateDB in comparison to the BIND, DIP, MINT, IntAct and BioGRID databases (i.e. >80%).
TextSentencer_T71 12853-12950 Sentence denotes C) Interactions in A which were also curated by the BioGRID, BIND, DIP, MINT or IntACT databases.
TextSentencer_T71 12853-12950 Sentence denotes C) Interactions in A which were also curated by the BioGRID, BIND, DIP, MINT or IntACT databases.
TextSentencer_T72 12951-13115 Sentence denotes This figure illustrates how InnateDB curation greatly enhances our knowledge of innate immunity-relevant interaction networks, a key step in systems-level analyses.
TextSentencer_T72 12951-13115 Sentence denotes This figure illustrates how InnateDB curation greatly enhances our knowledge of innate immunity-relevant interaction networks, a key step in systems-level analyses.
TextSentencer_T73 13116-13145 Sentence denotes The RIG-I signalling pathway.
TextSentencer_T73 13116-13145 Sentence denotes The RIG-I signalling pathway.
TextSentencer_T74 13146-13191 Sentence denotes A) KEGG pathway diagram of the RIG-I pathway.
TextSentencer_T74 13146-13191 Sentence denotes A) KEGG pathway diagram of the RIG-I pathway.
TextSentencer_T75 13192-13381 Sentence denotes B) A network of all InnateDB annotated molecular interactions between components of the RIG-I pathway highlights the additional level of complexity that is not conveyed in the KEGG diagram.
TextSentencer_T75 13192-13381 Sentence denotes B) A network of all InnateDB annotated molecular interactions between components of the RIG-I pathway highlights the additional level of complexity that is not conveyed in the KEGG diagram.
TextSentencer_T76 13382-13496 Sentence denotes Edges coloured red represent phosphorylation interactions; edges coloured blue represent protein-DNA interactions.
TextSentencer_T76 13382-13496 Sentence denotes Edges coloured red represent phosphorylation interactions; edges coloured blue represent protein-DNA interactions.
TextSentencer_T77 13497-13752 Sentence denotes C) A network of all InnateDB annotated molecular interactions between components of the RIG-I pathway and all other annotated interaction partners reveals the potential for cross-talk between RIG-I pathway components and many other molecules and pathways.
TextSentencer_T77 13497-13752 Sentence denotes C) A network of all InnateDB annotated molecular interactions between components of the RIG-I pathway and all other annotated interaction partners reveals the potential for cross-talk between RIG-I pathway components and many other molecules and pathways.
TextSentencer_T78 13753-14037 Sentence denotes Networks were constructed using InnateDB (http://www.innatedb.com/batchSearchInit.jsp) and were visualised in Cytoscape 2.6.3 using the Cerebral plugin. huge complexity in the signalling response and crosstalk and/or interchange between a large number of other molecules and pathways.
TextSentencer_T78 13753-14037 Sentence denotes Networks were constructed using InnateDB (http://www.innatedb.com/batchSearchInit.jsp) and were visualised in Cytoscape 2.6.3 using the Cerebral plugin. huge complexity in the signalling response and crosstalk and/or interchange between a large number of other molecules and pathways.
TextSentencer_T79 14038-14417 Sentence denotes The network of InnateDB curated human interactions was analysed using the cytoHubba plugin [30] (http:// hub.iis.sinica.edu.tw/cytoHubba/) for Cytoscape 2.6.3 [31] to investigate a variety of properties of this network including the identification of network hubs and bottlenecks (see below for definitions), which are likely to represent the key regulatory nodes in the network.
TextSentencer_T79 14038-14417 Sentence denotes The network of InnateDB curated human interactions was analysed using the cytoHubba plugin [30] (http:// hub.iis.sinica.edu.tw/cytoHubba/) for Cytoscape 2.6.3 [31] to investigate a variety of properties of this network including the identification of network hubs and bottlenecks (see below for definitions), which are likely to represent the key regulatory nodes in the network.
TextSentencer_T80 14418-14540 Sentence denotes The top 50 hubs (i.e. highly connected nodes) in this network were identified by using the "Degree" algorithm ( Table 1 ).
TextSentencer_T80 14418-14540 Sentence denotes The top 50 hubs (i.e. highly connected nodes) in this network were identified by using the "Degree" algorithm ( Table 1 ).
TextSentencer_T81 14541-14743 Sentence denotes The hub nodes were, in particular, highly enriched for proteins involved in the TLR and NFB signalling pathways [MYD88, TRAF6, IRAK1, CHUK (IKBKA), IKBKB, IKBKG (NEMO), NFKB1, RELA, MAP3K7 (TAK1), etc].
TextSentencer_T81 14541-14743 Sentence denotes The hub nodes were, in particular, highly enriched for proteins involved in the TLR and NFB signalling pathways [MYD88, TRAF6, IRAK1, CHUK (IKBKA), IKBKB, IKBKG (NEMO), NFKB1, RELA, MAP3K7 (TAK1), etc].
TextSentencer_T82 14744-14869 Sentence denotes In addition to the NFB transcription factor subunits, a number of IRF and STAT transcription factors were identified as hubs.
TextSentencer_T82 14744-14869 Sentence denotes In addition to the NFB transcription factor subunits, a number of IRF and STAT transcription factors were identified as hubs.
TextSentencer_T83 14870-14969 Sentence denotes There were also a number of hub proteins that do not currently have known roles in innate immunity.
TextSentencer_T83 14870-14969 Sentence denotes There were also a number of hub proteins that do not currently have known roles in innate immunity.
TextSentencer_T84 14970-15065 Sentence denotes These provide potentially new regulators of innate immunity that warrant further investigation.
TextSentencer_T84 14970-15065 Sentence denotes These provide potentially new regulators of innate immunity that warrant further investigation.
TextSentencer_T85 15066-15160 Sentence denotes The Hubba software also allows one to predict proteins that act as bottlenecks in the network.
TextSentencer_T85 15066-15160 Sentence denotes The Hubba software also allows one to predict proteins that act as bottlenecks in the network.
TextSentencer_T86 15161-15296 Sentence denotes Bottlenecks are network nodes that are the key connector proteins in a network and have many "shortest paths" going through them [32] .
TextSentencer_T86 15161-15296 Sentence denotes Bottlenecks are network nodes that are the key connector proteins in a network and have many "shortest paths" going through them [32] .
TextSentencer_T87 15297-15389 Sentence denotes The majority of hub proteins were also identified amongst the top 50 bottlenecks (Table 1) .
TextSentencer_T87 15297-15389 Sentence denotes The majority of hub proteins were also identified amongst the top 50 bottlenecks (Table 1) .
TextSentencer_T88 15390-15492 Sentence denotes The InnateDB curated interactome includes more than 2,000 human genes and more than 1,000 mouse genes.
TextSentencer_T88 15390-15492 Sentence denotes The InnateDB curated interactome includes more than 2,000 human genes and more than 1,000 mouse genes.
TextSentencer_T89 15493-15663 Sentence denotes The InnateDB pathway and Gene Ontology tools have been used to investigate the pathways and biological processes which are statistically over-represented in this dataset.
TextSentencer_T89 15493-15663 Sentence denotes The InnateDB pathway and Gene Ontology tools have been used to investigate the pathways and biological processes which are statistically over-represented in this dataset.
TextSentencer_T90 15664-15808 Sentence denotes Given that the majority of interactions in Inna-teDB involve human molecules, we have focused these analyses on human genes (Additional file 1).
TextSentencer_T90 15664-15808 Sentence denotes Given that the majority of interactions in Inna-teDB involve human molecules, we have focused these analyses on human genes (Additional file 1).
TextSentencer_T91 15809-15978 Sentence denotes Unsurprisingly, a range of innate immunity pathways are statistically over-represented in this dataset, including TLR, RIG-I, NLR and other pathways (Additional file 2).
TextSentencer_T91 15809-15978 Sentence denotes Unsurprisingly, a range of innate immunity pathways are statistically over-represented in this dataset, including TLR, RIG-I, NLR and other pathways (Additional file 2).
TextSentencer_T92 15979-16212 Sentence denotes Perhaps highlighting an increased appreciation of the links between innate and adaptive immunity [2] , several pathways of relevance to adaptive immunity were also overrepresented, including T and B cell receptor signalling pathways.
TextSentencer_T92 15979-16212 Sentence denotes Perhaps highlighting an increased appreciation of the links between innate and adaptive immunity [2] , several pathways of relevance to adaptive immunity were also overrepresented, including T and B cell receptor signalling pathways.
TextSentencer_T93 16213-16347 Sentence denotes This network of genes and proteins involved in both innate and adaptive immunity underscores the interconnectivity of the two systems.
TextSentencer_T93 16213-16347 Sentence denotes This network of genes and proteins involved in both innate and adaptive immunity underscores the interconnectivity of the two systems.
TextSentencer_T94 16348-16562 Sentence denotes Interestingly, the network is also enriched in pathways annotated to be involved in cancer (e.g. KEGG pathways -Pathways in cancer; Prostate cancer; Pancreatic cancer; Colorectal cancer; Chronic myeloid leukaemia).
TextSentencer_T94 16348-16562 Sentence denotes Interestingly, the network is also enriched in pathways annotated to be involved in cancer (e.g. KEGG pathways -Pathways in cancer; Prostate cancer; Pancreatic cancer; Colorectal cancer; Chronic myeloid leukaemia).
TextSentencer_T95 16563-16717 Sentence denotes This may be due to overlap between these cancer pathways with apoptosis (also over-represented) and other relevant pathways such as TGFβ signalling [33] .
TextSentencer_T95 16563-16717 Sentence denotes This may be due to overlap between these cancer pathways with apoptosis (also over-represented) and other relevant pathways such as TGFβ signalling [33] .
TextSentencer_T96 16718-16908 Sentence denotes The importance of apoptosis in the innate immune response is well known [34, 35] , however, the connection between innate immunity and cancer is now also becoming more established [36, 37] .
TextSentencer_T96 16718-16908 Sentence denotes The importance of apoptosis in the innate immune response is well known [34, 35] , however, the connection between innate immunity and cancer is now also becoming more established [36, 37] .
TextSentencer_T97 16909-17095 Sentence denotes Other interesting over-represented pathways include the Insulin signalling pathway, Wnt signalling, Ubiquitin mediated proteolysis, and Endocytosis among many others (Additional file 2).
TextSentencer_T97 16909-17095 Sentence denotes Other interesting over-represented pathways include the Insulin signalling pathway, Wnt signalling, Ubiquitin mediated proteolysis, and Endocytosis among many others (Additional file 2).
TextSentencer_T98 17096-17214 Sentence denotes Intriguingly, there is growing evidence of an contribution of a dysregulated innate immune response to diabetes [38] .
TextSentencer_T98 17096-17214 Sentence denotes Intriguingly, there is growing evidence of an contribution of a dysregulated innate immune response to diabetes [38] .
TextSentencer_T99 17215-17414 Sentence denotes Links between Wnt signalling and innate immunity are also becoming apparent [39] , while the involvement of ubiquitin mediated proteolysis and endocytosis in innate immunity are well known [40, 41] .
TextSentencer_T99 17215-17414 Sentence denotes Links between Wnt signalling and innate immunity are also becoming apparent [39] , while the involvement of ubiquitin mediated proteolysis and endocytosis in innate immunity are well known [40, 41] .
TextSentencer_T100 17415-17578 Sentence denotes The InnateDB curated genes are also over-represented in pathways that do not have well established links to innate immunity, for example, the neurotrophin pathway.
TextSentencer_T100 17415-17578 Sentence denotes The InnateDB curated genes are also over-represented in pathways that do not have well established links to innate immunity, for example, the neurotrophin pathway.
TextSentencer_T101 17579-17720 Sentence denotes Neurotrophins are a family of proteins involved in neural cell differentiation and survival and may be involved in Alzheimer's disease [42] .
TextSentencer_T101 17579-17720 Sentence denotes Neurotrophins are a family of proteins involved in neural cell differentiation and survival and may be involved in Alzheimer's disease [42] .
TextSentencer_T102 17721-17823 Sentence denotes So far, there is only limited evidence of a relationship between neurotrophins and inflammation [43] .
TextSentencer_T102 17721-17823 Sentence denotes So far, there is only limited evidence of a relationship between neurotrophins and inflammation [43] .
TextSentencer_T103 17824-18032 Sentence denotes Although there are likely to be several reasons why this pathway would be overrepresented in the InnateDB curated interactome, it is tempting to speculate about links between innate immunity and this pathway.
TextSentencer_T103 17824-18032 Sentence denotes Although there are likely to be several reasons why this pathway would be overrepresented in the InnateDB curated interactome, it is tempting to speculate about links between innate immunity and this pathway.
TextSentencer_T104 18033-18180 Sentence denotes The InnateDB interactome provides a wealth of data for further investigation of the links between innate immunity and other processes and pathways.
TextSentencer_T104 18033-18180 Sentence denotes The InnateDB interactome provides a wealth of data for further investigation of the links between innate immunity and other processes and pathways.
TextSentencer_T105 18181-18473 Sentence denotes Gene Ontology analysis paints a similar picture to the pathway analysis with terms such as innate immune response, inflammatory response, response to virus, apoptosis, cytokine activity, and signal transduction all being in the top 20 most statistically significant terms (Additional file 3).
TextSentencer_T105 18181-18473 Sentence denotes Gene Ontology analysis paints a similar picture to the pathway analysis with terms such as innate immune response, inflammatory response, response to virus, apoptosis, cytokine activity, and signal transduction all being in the top 20 most statistically significant terms (Additional file 3).
TextSentencer_T106 18474-18570 Sentence denotes Reassuringly, innate immune response is the most over-represented term (corrected P = 2 e-163 ).
TextSentencer_T106 18474-18570 Sentence denotes Reassuringly, innate immune response is the most over-represented term (corrected P = 2 e-163 ).
TextSentencer_T107 18571-18731 Sentence denotes Other terms such as protein kinase activity and nucleotide binding reflect the large number of phosphorylation and protein-DNA interactions curated by InnateDB.
TextSentencer_T107 18571-18731 Sentence denotes Other terms such as protein kinase activity and nucleotide binding reflect the large number of phosphorylation and protein-DNA interactions curated by InnateDB.
TextSentencer_T108 18732-18814 Sentence denotes The InnateDB curation team has annotated more than 2,500 protein-DNA interactions.
TextSentencer_T108 18732-18814 Sentence denotes The InnateDB curation team has annotated more than 2,500 protein-DNA interactions.
TextSentencer_T109 18815-19037 Sentence denotes Aside from these curated interactions, we have also investigated which transcription factor binding sites are over-represented in the promoter regions of human genes in the InnateDB curated interactome (Additional file 4).
TextSentencer_T109 18815-19037 Sentence denotes Aside from these curated interactions, we have also investigated which transcription factor binding sites are over-represented in the promoter regions of human genes in the InnateDB curated interactome (Additional file 4).
TextSentencer_T110 19038-19193 Sentence denotes Perhaps unsurprisingly, given the central role of NFB in innate immunity [44] , binding sites for its subunits are the most statistically over-represented.
TextSentencer_T110 19038-19193 Sentence denotes Perhaps unsurprisingly, given the central role of NFB in innate immunity [44] , binding sites for its subunits are the most statistically over-represented.
TextSentencer_T111 19194-19265 Sentence denotes The interferon regulatory factor, IRF8, is also over-represented [45] .
TextSentencer_T111 19194-19265 Sentence denotes The interferon regulatory factor, IRF8, is also over-represented [45] .
TextSentencer_T112 19266-19414 Sentence denotes Other IRFs, including IRF1, IRF2 and IRF7 are overrepresented but these are only statistically significant prior to correction for multiple testing.
TextSentencer_T112 19266-19414 Sentence denotes Other IRFs, including IRF1, IRF2 and IRF7 are overrepresented but these are only statistically significant prior to correction for multiple testing.
TextSentencer_T113 19415-19602 Sentence denotes Similarly, prior to correction for multiple testing, there are many other well-known innate immunity relevant transcription factors over-represented including CREB1, CEBPB, AP1 and STAT1.
TextSentencer_T113 19415-19602 Sentence denotes Similarly, prior to correction for multiple testing, there are many other well-known innate immunity relevant transcription factors over-represented including CREB1, CEBPB, AP1 and STAT1.
TextSentencer_T114 19603-19796 Sentence denotes In addition to these, there are a number of other transcription factors that do not have well known roles in innate immunity and would be potentially interesting to investigate in this context.
TextSentencer_T114 19603-19796 Sentence denotes In addition to these, there are a number of other transcription factors that do not have well known roles in innate immunity and would be potentially interesting to investigate in this context.
TextSentencer_T115 19797-19869 Sentence denotes ATF6, for example, does not have a well defined role in innate immunity.
TextSentencer_T115 19797-19869 Sentence denotes ATF6, for example, does not have a well defined role in innate immunity.
TextSentencer_T116 19870-20094 Sentence denotes This ER stress-regulated transcription factor, however, is a key component of the unfolded protein response (UPR), which is induced in response to and can be modulated by several viruses and bacterial toxins [46] [47] [48] .
TextSentencer_T116 19870-20094 Sentence denotes This ER stress-regulated transcription factor, however, is a key component of the unfolded protein response (UPR), which is induced in response to and can be modulated by several viruses and bacterial toxins [46] [47] [48] .
TextSentencer_T117 20095-20173 Sentence denotes ATF4, which is also over-represented, is also involved in this response [49] .
TextSentencer_T117 20095-20173 Sentence denotes ATF4, which is also over-represented, is also involved in this response [49] .
TextSentencer_T118 20174-20277 Sentence denotes A key link between the UPR and innate immunity in C. elegans has very recently been demonstrated [50] .
TextSentencer_T118 20174-20277 Sentence denotes A key link between the UPR and innate immunity in C. elegans has very recently been demonstrated [50] .
TextSentencer_T119 20278-20376 Sentence denotes The importance of microRNAs (miRNAs) as regulators of innate immunity is now becoming clear [28] .
TextSentencer_T119 20278-20376 Sentence denotes The importance of microRNAs (miRNAs) as regulators of innate immunity is now becoming clear [28] .
TextSentencer_T120 20377-20552 Sentence denotes We have used the DIANA-mirExTra web server (http:// www.microrna.gr/mirextra) [51] to identify miRNA target motifs that are over-represented in our curated human gene dataset.
TextSentencer_T120 20377-20552 Sentence denotes We have used the DIANA-mirExTra web server (http:// www.microrna.gr/mirextra) [51] to identify miRNA target motifs that are over-represented in our curated human gene dataset.
TextSentencer_T121 20553-20677 Sentence denotes Due to the short size of the miRNA motifs, a large number of miRNAs were identified as over-represented (Additional file 5).
TextSentencer_T121 20553-20677 Sentence denotes Due to the short size of the miRNA motifs, a large number of miRNAs were identified as over-represented (Additional file 5).
TextSentencer_T122 20678-20933 Sentence denotes These include miRNAs with known roles in innate immunity or inflammation. miR-105, for example, has been shown to regulate the protein expression of TLR2 in human keratinocytes [52] , while miR-182 expression is a biomarker for patients with sepsis [53] .
TextSentencer_T122 20678-20933 Sentence denotes These include miRNAs with known roles in innate immunity or inflammation. miR-105, for example, has been shown to regulate the protein expression of TLR2 in human keratinocytes [52] , while miR-182 expression is a biomarker for patients with sepsis [53] .
TextSentencer_T123 20934-21132 Sentence denotes Others have roles in pathways enriched in the InnateDB curated interactome, including miR-200 which regulates insulin signalling [54] , and miR-101 and miR-214 that are involved in cancer [55, 56] .
TextSentencer_T123 20934-21132 Sentence denotes Others have roles in pathways enriched in the InnateDB curated interactome, including miR-200 which regulates insulin signalling [54] , and miR-101 and miR-214 that are involved in cancer [55, 56] .
TextSentencer_T124 21133-21303 Sentence denotes As with the other preliminary analyses discussed above, this dataset provides a wealth of information to identify new potentially important regulators of innate immunity.
TextSentencer_T124 21133-21303 Sentence denotes As with the other preliminary analyses discussed above, this dataset provides a wealth of information to identify new potentially important regulators of innate immunity.
TextSentencer_T125 21304-21594 Sentence denotes The goal of manual curation in InnateDB is to accurately and richly annotate molecular interactions and pathways of relevance to the innate immune system in human and mouse and as demonstrated above this curation process provides an invaluable data source for investigating innate immunity.
TextSentencer_T125 21304-21594 Sentence denotes The goal of manual curation in InnateDB is to accurately and richly annotate molecular interactions and pathways of relevance to the innate immune system in human and mouse and as demonstrated above this curation process provides an invaluable data source for investigating innate immunity.
TextSentencer_T126 21595-21804 Sentence denotes Given that the quality of this resource is dependent on our curation process, a discussion of the InnateDB curation approach and our novel software, which enables accurate, standardised curation, is warranted.
TextSentencer_T126 21595-21804 Sentence denotes Given that the quality of this resource is dependent on our curation process, a discussion of the InnateDB curation approach and our novel software, which enables accurate, standardised curation, is warranted.
TextSentencer_T127 21805-21922 Sentence denotes Details of molecular interactions are extracted through review of relevant publications in the biomedical literature.
TextSentencer_T127 21805-21922 Sentence denotes Details of molecular interactions are extracted through review of relevant publications in the biomedical literature.
TextSentencer_T128 21923-22162 Sentence denotes Curation is primarily carried out in a pathwaycentric way, whereby curators systematically review all of the available literature describing interactions that involve members of a particular innate immunity pathway (e.g. RIG-I signalling).
TextSentencer_T128 21923-22162 Sentence denotes Curation is primarily carried out in a pathwaycentric way, whereby curators systematically review all of the available literature describing interactions that involve members of a particular innate immunity pathway (e.g. RIG-I signalling).
TextSentencer_T129 22163-22414 Sentence denotes Review articles, pathway databases and other sources are used to define the components of a pathway and then all molecular interactions between these genes and their encoded products and any other molecule (protein, DNA, RNA) are reviewed and curated.
TextSentencer_T129 22163-22414 Sentence denotes Review articles, pathway databases and other sources are used to define the components of a pathway and then all molecular interactions between these genes and their encoded products and any other molecule (protein, DNA, RNA) are reviewed and curated.
TextSentencer_T130 22415-22628 Sentence denotes Molecular interactions for each pathway member are systematically curated, although priority is given to publications and experiments that are not already described in InnateDB (or the other integrated databases).
TextSentencer_T130 22415-22628 Sentence denotes Molecular interactions for each pathway member are systematically curated, although priority is given to publications and experiments that are not already described in InnateDB (or the other integrated databases).
TextSentencer_T131 22629-22841 Sentence denotes Importantly, interactions are curated between molecules in the pathway and all other interactors regardless of whether the interacting molecule is a member of the pathway or has any known role in innate immunity.
TextSentencer_T131 22629-22841 Sentence denotes Importantly, interactions are curated between molecules in the pathway and all other interactors regardless of whether the interacting molecule is a member of the pathway or has any known role in innate immunity.
TextSentencer_T132 22842-23070 Sentence denotes This allows InnateDB to expand on linear views of pathways to develop a more comprehensive interaction network perspective, highlighting potential cross-talk between pathways and/or prospective novel pathway members (Figure 2 ).
TextSentencer_T132 22842-23070 Sentence denotes This allows InnateDB to expand on linear views of pathways to develop a more comprehensive interaction network perspective, highlighting potential cross-talk between pathways and/or prospective novel pathway members (Figure 2 ).
TextSentencer_T133 23071-23234 Sentence denotes This pathway-centric process increases curation efficiency as one publication often describes molecular interactions involving several different pathway molecules.
TextSentencer_T133 23071-23234 Sentence denotes This pathway-centric process increases curation efficiency as one publication often describes molecular interactions involving several different pathway molecules.
TextSentencer_T134 23235-23337 Sentence denotes Systematically curated pathways are scheduled for frequent re-curation as the field is moving quickly.
TextSentencer_T134 23235-23337 Sentence denotes Systematically curated pathways are scheduled for frequent re-curation as the field is moving quickly.
TextSentencer_T135 23338-23482 Sentence denotes In addition to this approach, new publications on innate immunity are also assessed on a daily basis to identify novel interactions of interest.
TextSentencer_T135 23338-23482 Sentence denotes In addition to this approach, new publications on innate immunity are also assessed on a daily basis to identify novel interactions of interest.
TextSentencer_T136 23483-23665 Sentence denotes Priority is given to the most recent publications, ensuring that InnateDB has a fast turnaround time for incorporating new information on the most current research into the database.
TextSentencer_T136 23483-23665 Sentence denotes Priority is given to the most recent publications, ensuring that InnateDB has a fast turnaround time for incorporating new information on the most current research into the database.
TextSentencer_T137 23666-23979 Sentence denotes Furthermore, the focus of curation efforts on a specific area (i.e. innate immunity) rather than on curating all molecular interactions in general is of significant benefit -ensuring that the curation team develops considerable expertise in assessing the relevant publications and in-depth knowledge of the field.
TextSentencer_T137 23666-23979 Sentence denotes Furthermore, the focus of curation efforts on a specific area (i.e. innate immunity) rather than on curating all molecular interactions in general is of significant benefit -ensuring that the curation team develops considerable expertise in assessing the relevant publications and in-depth knowledge of the field.
TextSentencer_T138 23980-24499 Sentence denotes The InnateDB curation system (http://www.innatedb. com/dashboard) is a novel web-based platform that has been designed as part of the curation project to allow the submission of detailed contextual annotation on each interaction to the database in a manner that is compliant with the recently proposed "minimum information required for reporting a molecular interaction experiment" (MIMIx) guidelines [57] , and in compliance with the Proteomics Standards Initiative Molecular Interaction (PSI-MI) 2.5 XML format [58] .
TextSentencer_T138 23980-24499 Sentence denotes The InnateDB curation system (http://www.innatedb. com/dashboard) is a novel web-based platform that has been designed as part of the curation project to allow the submission of detailed contextual annotation on each interaction to the database in a manner that is compliant with the recently proposed "minimum information required for reporting a molecular interaction experiment" (MIMIx) guidelines [57] , and in compliance with the Proteomics Standards Initiative Molecular Interaction (PSI-MI) 2.5 XML format [58] .
TextSentencer_T139 24500-24917 Sentence denotes Such annotation includes the supporting publication; the participant molecules; the molecule type; the organism; the biological role; the interaction detection method; the host system (in vitro, in vivo, ex vivo); the host organism; the interaction type; the cell, cell-line and tissue types; cell status (primary/cell line); the experimental role; the participant identification method and sub-cellular localisation.
TextSentencer_T139 24500-24917 Sentence denotes Such annotation includes the supporting publication; the participant molecules; the molecule type; the organism; the biological role; the interaction detection method; the host system (in vitro, in vivo, ex vivo); the host organism; the interaction type; the cell, cell-line and tissue types; cell status (primary/cell line); the experimental role; the participant identification method and sub-cellular localisation.
TextSentencer_T140 24918-25013 Sentence denotes The curation system is implemented using the opensource framework CakePHP (http://cakephp.org).
TextSentencer_T140 24918-25013 Sentence denotes The curation system is implemented using the opensource framework CakePHP (http://cakephp.org).
TextSentencer_T141 25014-25170 Sentence denotes On the web interface of the system, browser-side scripting technology with JavaScript and JQuery are utilised to provide a more interactive user experience.
TextSentencer_T141 25014-25170 Sentence denotes On the web interface of the system, browser-side scripting technology with JavaScript and JQuery are utilised to provide a more interactive user experience.
TextSentencer_T142 25171-25290 Sentence denotes Submitted interactions are stored in a MySQL database and are migrated to the public database tables on a weekly basis.
TextSentencer_T142 25171-25290 Sentence denotes Submitted interactions are stored in a MySQL database and are migrated to the public database tables on a weekly basis.
TextSentencer_T143 25291-25346 Sentence denotes Note that a user account is required to use the system.
TextSentencer_T143 25291-25346 Sentence denotes Note that a user account is required to use the system.
TextSentencer_T144 25347-25649 Sentence denotes The system has been designed to minimise the amount of free-text information that needs to be entered by the curator and instead, it utilises, where possible, a series of drop-down menus of PSI-MI [59] , Open Biomedical Ontology (OBO) [60] or Gene Ontology [61] controlled vocabulary terms (Figure 3 ).
TextSentencer_T144 25347-25649 Sentence denotes The system has been designed to minimise the amount of free-text information that needs to be entered by the curator and instead, it utilises, where possible, a series of drop-down menus of PSI-MI [59] , Open Biomedical Ontology (OBO) [60] or Gene Ontology [61] controlled vocabulary terms (Figure 3 ).
TextSentencer_T145 25650-25741 Sentence denotes There are only 4 free-text fields of the 20+ fields that are used to curate an interaction.
TextSentencer_T145 25650-25741 Sentence denotes There are only 4 free-text fields of the 20+ fields that are used to curate an interaction.
TextSentencer_T146 25742-25903 Sentence denotes Two of these fields relate to additional comments that curators can record, such as details of any experimental conditions relevant to detecting the interaction.
TextSentencer_T146 25742-25903 Sentence denotes Two of these fields relate to additional comments that curators can record, such as details of any experimental conditions relevant to detecting the interaction.
TextSentencer_T147 25904-26016 Sentence denotes Such comments include, for example, stimulation with a particular cytokine, information on mutations, tags, etc.
TextSentencer_T147 25904-26016 Sentence denotes Such comments include, for example, stimulation with a particular cytokine, information on mutations, tags, etc.
TextSentencer_T148 26017-26126 Sentence denotes Another free-text field is the full name for the interaction for which we have established a standard format.
TextSentencer_T148 26017-26126 Sentence denotes Another free-text field is the full name for the interaction for which we have established a standard format.
TextSentencer_T149 26127-26256 Sentence denotes The fourth free-text field is for the PubMed ID (PMID), however, this must be validated before it will be accepted by the system.
TextSentencer_T149 26127-26256 Sentence denotes The fourth free-text field is for the PubMed ID (PMID), however, this must be validated before it will be accepted by the system.
TextSentencer_T150 26257-26365 Sentence denotes When a curator enters a PMID, the abstract for this PMID is automatically retrieved from NCBI and displayed.
TextSentencer_T150 26257-26365 Sentence denotes When a curator enters a PMID, the abstract for this PMID is automatically retrieved from NCBI and displayed.
TextSentencer_T151 26366-26462 Sentence denotes The curator must then confirm that this is the correct abstract before the PMID will be entered.
TextSentencer_T151 26366-26462 Sentence denotes The curator must then confirm that this is the correct abstract before the PMID will be entered.
TextSentencer_T152 26463-26591 Sentence denotes An interaction may have two participants, in the case of binary interactions, or multiple participants in the case of complexes.
TextSentencer_T152 26463-26591 Sentence denotes An interaction may have two participants, in the case of binary interactions, or multiple participants in the case of complexes.
TextSentencer_T153 26592-26673 Sentence denotes Self interactions are annotated as binary interactions with the same participant.
TextSentencer_T153 26592-26673 Sentence denotes Self interactions are annotated as binary interactions with the same participant.
TextSentencer_T154 26674-26797 Sentence denotes Network and pathway visualisation in InnateDB is carried out using Cerebral (Cell Region-Based Rendering And Layout) [62] .
TextSentencer_T154 26674-26797 Sentence denotes Network and pathway visualisation in InnateDB is carried out using Cerebral (Cell Region-Based Rendering And Layout) [62] .
TextSentencer_T155 26798-27002 Sentence denotes Cerebral is a plugin for the Cytoscape biomolecular interaction viewer [31] that generates more biologically intuitive pathway-like layouts of networks using subcellular localisation and other annotation.
TextSentencer_T155 26798-27002 Sentence denotes Cerebral is a plugin for the Cytoscape biomolecular interaction viewer [31] that generates more biologically intuitive pathway-like layouts of networks using subcellular localisation and other annotation.
TextSentencer_T156 27003-27159 Sentence denotes In the version of Cerebral launched from InnateDB, complexes are displayed as separate nodes with each participant shown as an interaction with the complex.
TextSentencer_T156 27003-27159 Sentence denotes In the version of Cerebral launched from InnateDB, complexes are displayed as separate nodes with each participant shown as an interaction with the complex.
TextSentencer_T157 27160-27209 Sentence denotes Such edges are labelled 'X is part of complex Y'.
TextSentencer_T157 27160-27209 Sentence denotes Such edges are labelled 'X is part of complex Y'.
TextSentencer_T158 27210-27379 Sentence denotes In this way, nodes representing complexes can be linked to other interactions in the network without inferring binary interactions between all participants in a complex.
TextSentencer_T158 27210-27379 Sentence denotes In this way, nodes representing complexes can be linked to other interactions in the network without inferring binary interactions between all participants in a complex.
TextSentencer_T159 27380-27565 Sentence denotes Each interaction participant is linked to InnateDB via a unique, stable, InnateDB molecule ID, which maps one-to-one with identifiers from the Ensembl database (http://www.ensembl.org).
TextSentencer_T159 27380-27565 Sentence denotes Each interaction participant is linked to InnateDB via a unique, stable, InnateDB molecule ID, which maps one-to-one with identifiers from the Ensembl database (http://www.ensembl.org).
TextSentencer_T160 27566-27764 Sentence denotes When a curator adds a participant, they enter the gene/protein name into a search field, InnateDB is then searched for all matching gene/ protein synonyms (both symbols and full names are searched).
TextSentencer_T160 27566-27764 Sentence denotes When a curator adds a participant, they enter the gene/protein name into a search field, InnateDB is then searched for all matching gene/ protein synonyms (both symbols and full names are searched).
TextSentencer_T161 27765-28028 Sentence denotes Although HGNC (HUGO Gene Nomenclature Committee) symbols are used for human participants [63] and Mouse Genome Database (MGD) symbols for mouse participants [64] , all known synonyms, full-names and other details for the participant are displayed for the curator.
TextSentencer_T161 27765-28028 Sentence denotes Although HGNC (HUGO Gene Nomenclature Committee) symbols are used for human participants [63] and Mouse Genome Database (MGD) symbols for mouse participants [64] , all known synonyms, full-names and other details for the participant are displayed for the curator.
TextSentencer_T162 28029-28089 Sentence denotes This reduces incidences of confusing alternative gene names.
TextSentencer_T162 28029-28089 Sentence denotes This reduces incidences of confusing alternative gene names.
TextSentencer_T163 28090-28235 Sentence denotes InnateDB also provides extensive cross-references to other major databases (CCDS, EMBL, Ensembl, Entrez Gene, HPRD, HUGO, OMIM, RefSeq, UniProt).
TextSentencer_T163 28090-28235 Sentence denotes InnateDB also provides extensive cross-references to other major databases (CCDS, EMBL, Ensembl, Entrez Gene, HPRD, HUGO, OMIM, RefSeq, UniProt).
TextSentencer_T164 28236-28331 Sentence denotes As mentioned, InnateDB currently only includes interactions involving human or mouse molecules.
TextSentencer_T164 28236-28331 Sentence denotes As mentioned, InnateDB currently only includes interactions involving human or mouse molecules.
TextSentencer_T165 28332-28403 Sentence denotes Hybrid interactions involving human and mouse participants are allowed.
TextSentencer_T165 28332-28403 Sentence denotes Hybrid interactions involving human and mouse participants are allowed.
TextSentencer_T166 28404-28574 Sentence denotes If no information about the participant species can be gathered from the paper or in other references, the authors of the paper are contacted to provide this information.
TextSentencer_T166 28404-28574 Sentence denotes If no information about the participant species can be gathered from the paper or in other references, the authors of the paper are contacted to provide this information.
TextSentencer_T167 28575-28960 Sentence denotes The most common interaction type among curated interactions is "physical association", however, there are also many more specific interaction types including over 700 phosphorylation interactions, more than 300 cleavage interactions, 85 ubiquitination interactions, and smaller numbers of other biochemical interactions including sumoylation, methylation, and acetylation interactions.
TextSentencer_T167 28575-28960 Sentence denotes The most common interaction type among curated interactions is "physical association", however, there are also many more specific interaction types including over 700 phosphorylation interactions, more than 300 cleavage interactions, 85 ubiquitination interactions, and smaller numbers of other biochemical interactions including sumoylation, methylation, and acetylation interactions.
TextSentencer_T168 28961-29037 Sentence denotes There are also over 300 transcriptional regulation interactions in InnateDB.
TextSentencer_T168 28961-29037 Sentence denotes There are also over 300 transcriptional regulation interactions in InnateDB.
TextSentencer_T169 29038-29217 Sentence denotes These interactions must be supported by evidence showing physical protein-DNA binding and evidence that this binding alters transcription, for example, through a luciferase assay.
TextSentencer_T169 29038-29217 Sentence denotes These interactions must be supported by evidence showing physical protein-DNA binding and evidence that this binding alters transcription, for example, through a luciferase assay.
TextSentencer_T170 29218-29375 Sentence denotes Each interaction, which is defined by the participant molecules and the interaction type, may have multiple lines of interaction evidence associated with it.
TextSentencer_T170 29218-29375 Sentence denotes Each interaction, which is defined by the participant molecules and the interaction type, may have multiple lines of interaction evidence associated with it.
TextSentencer_T171 29376-29496 Sentence denotes Interaction evidence refers to the experimental procedures and conditions that were reported to support the interaction.
TextSentencer_T171 29376-29496 Sentence denotes Interaction evidence refers to the experimental procedures and conditions that were reported to support the interaction.
TextSentencer_T172 29497-29628 Sentence denotes The same interaction may be supported by multiple different publications or different experiments reported in the same publication.
TextSentencer_T172 29497-29628 Sentence denotes The same interaction may be supported by multiple different publications or different experiments reported in the same publication.
TextSentencer_T173 29629-29760 Sentence denotes For convenience, interactions with multiple lines of evidence are grouped into a single nonredundant entry on the InnateDB website.
TextSentencer_T173 29629-29760 Sentence denotes For convenience, interactions with multiple lines of evidence are grouped into a single nonredundant entry on the InnateDB website.
TextSentencer_T174 29761-29919 Sentence denotes For detailed discussion of how evidence is curated in InnateDB please see the curation manual (http://www.innatedb. com/doc/InnateDB_2010_curation_guide.pdf).
TextSentencer_T174 29761-29919 Sentence denotes For detailed discussion of how evidence is curated in InnateDB please see the curation manual (http://www.innatedb. com/doc/InnateDB_2010_curation_guide.pdf).
TextSentencer_T175 29920-29969 Sentence denotes Interaction Evidence -which journals are curated?
TextSentencer_T175 29920-29969 Sentence denotes Interaction Evidence -which journals are curated?
TextSentencer_T176 29970-30123 Sentence denotes To date, more than 3,000 journal articles have been curated by InnateDB curators (see http://www.innatedb. com/statistics.jsp for up-to-date statistics).
TextSentencer_T176 29970-30123 Sentence denotes To date, more than 3,000 journal articles have been curated by InnateDB curators (see http://www.innatedb. com/statistics.jsp for up-to-date statistics).
TextSentencer_T177 30124-30363 Sentence denotes The curation team does not focus their efforts to any specific journalsrelevant articles are curated regardless of the journal in which they are published as long as they meet the appropriate quality standards for the interaction evidence.
TextSentencer_T177 30124-30363 Sentence denotes The curation team does not focus their efforts to any specific journalsrelevant articles are curated regardless of the journal in which they are published as long as they meet the appropriate quality standards for the interaction evidence.
TextSentencer_T178 30364-30439 Sentence denotes Indeed, at least one article has been curated from >200 different journals.
TextSentencer_T178 30364-30439 Sentence denotes Indeed, at least one article has been curated from >200 different journals.
TextSentencer_T179 30440-30524 Sentence denotes That said, more than 70% of curated articles have come from 20 journals (Figure 4) .
TextSentencer_T179 30440-30524 Sentence denotes That said, more than 70% of curated articles have come from 20 journals (Figure 4) .
TextSentencer_T180 30525-30733 Sentence denotes It is worth noting that many of the journals in this top 20 would not be considered to be immunology journals, underscoring the importance of not limiting curation efforts to journals perceived as "relevant".
TextSentencer_T180 30525-30733 Sentence denotes It is worth noting that many of the journals in this top 20 would not be considered to be immunology journals, underscoring the importance of not limiting curation efforts to journals perceived as "relevant".
TextSentencer_T181 30734-30830 Sentence denotes More than 800 articles, for example, have been curated from the Journal of Biological Chemistry.
TextSentencer_T181 30734-30830 Sentence denotes More than 800 articles, for example, have been curated from the Journal of Biological Chemistry.
TextSentencer_T182 30831-30903 Sentence denotes The Almost all other curated articles were published in the late 1990's.
TextSentencer_T182 30831-30903 Sentence denotes The Almost all other curated articles were published in the late 1990's.
TextSentencer_T183 30904-31130 Sentence denotes The interactome is not a single static entity and is very much dependent on the context of the particular celltype under investigation, thus detailed contextual annotation of interactions has the potential to be very valuable.
TextSentencer_T183 30904-31130 Sentence denotes The interactome is not a single static entity and is very much dependent on the context of the particular celltype under investigation, thus detailed contextual annotation of interactions has the potential to be very valuable.
TextSentencer_T184 31131-31335 Sentence denotes Although curated interactions in InnateDB are annotated in a wide range of cell and tissue types, the majority of these interactions stem from studies involving cell lines (87%) rather than primary cells.
TextSentencer_T184 31131-31335 Sentence denotes Although curated interactions in InnateDB are annotated in a wide range of cell and tissue types, the majority of these interactions stem from studies involving cell lines (87%) rather than primary cells.
TextSentencer_T185 31336-31474 Sentence denotes For primary cell interactions, macrophages represent the most prevalent cell-type, although less than 200 interactions have been recorded.
TextSentencer_T185 31336-31474 Sentence denotes For primary cell interactions, macrophages represent the most prevalent cell-type, although less than 200 interactions have been recorded.
TextSentencer_T186 31475-31544 Sentence denotes Epithelial cell derived lines are the most abundant cell line (~30%).
TextSentencer_T186 31475-31544 Sentence denotes Epithelial cell derived lines are the most abundant cell line (~30%).
TextSentencer_T187 31545-31621 Sentence denotes Additionally, there are approximately 300 macrophage cell line interactions.
TextSentencer_T187 31545-31621 Sentence denotes Additionally, there are approximately 300 macrophage cell line interactions.
TextSentencer_T188 31622-31825 Sentence denotes What is clear is that cell-type specific interaction maps are not currently feasible from this type of data and large-scale efforts to map the interactomes of particular cell-types are urgently required.
TextSentencer_T188 31622-31825 Sentence denotes What is clear is that cell-type specific interaction maps are not currently feasible from this type of data and large-scale efforts to map the interactomes of particular cell-types are urgently required.
TextSentencer_T189 31826-31993 Sentence denotes Curated interactions in InnateDB are supported by a broad range of interaction detection methods, including X-ray crystallography, yeast two-hybrids and GST pulldowns.
TextSentencer_T189 31826-31993 Sentence denotes Curated interactions in InnateDB are supported by a broad range of interaction detection methods, including X-ray crystallography, yeast two-hybrids and GST pulldowns.
TextSentencer_T190 31994-32111 Sentence denotes The most abundant detection method, however, is coimmunoprecipitation which accounts for nearly half of all evidence.
TextSentencer_T190 31994-32111 Sentence denotes The most abundant detection method, however, is coimmunoprecipitation which accounts for nearly half of all evidence.
TextSentencer_T191 32112-32285 Sentence denotes Aside from annotating innate immunity interactions and pathways, the InnateDB curation team has also begun to annotate which genes have a role in the innate immune response.
TextSentencer_T191 32112-32285 Sentence denotes Aside from annotating innate immunity interactions and pathways, the InnateDB curation team has also begun to annotate which genes have a role in the innate immune response.
TextSentencer_T192 32286-32523 Sentence denotes This was initiated because Gene Ontology annotation [61] of the innate immune response is limited to a quite small number of genes, and our effort reflects a desire in the research community to have a defined list of innate immune genes.
TextSentencer_T192 32286-32523 Sentence denotes This was initiated because Gene Ontology annotation [61] of the innate immune response is limited to a quite small number of genes, and our effort reflects a desire in the research community to have a defined list of innate immune genes.
TextSentencer_T193 32524-32748 Sentence denotes For innate immune gene annotation, curators employ an internal annotation tool in the InnateDB curation system to associate relevant genes with publications that provide evidence of a role of a given gene in innate immunity.
TextSentencer_T193 32524-32748 Sentence denotes For innate immune gene annotation, curators employ an internal annotation tool in the InnateDB curation system to associate relevant genes with publications that provide evidence of a role of a given gene in innate immunity.
TextSentencer_T194 32749-32949 Sentence denotes In addition to a link to the relevant publication(s), the curators provide a one-line summary of the role, similar to Entrez Gen-eRIFs (http://www.ncbi.nlm.nih.gov/projects/GeneRIF/ GeneRIFhelp.html).
TextSentencer_T194 32749-32949 Sentence denotes In addition to a link to the relevant publication(s), the curators provide a one-line summary of the role, similar to Entrez Gen-eRIFs (http://www.ncbi.nlm.nih.gov/projects/GeneRIF/ GeneRIFhelp.html).
TextSentencer_T195 32950-33190 Sentence denotes Such genes are also automatically associated/tagged with the Gene Ontology term "innate immune response" in InnateDB, providing a more comprehensive list of such genes for use by the InnateDB Gene Ontology over-representation analysis tool.
TextSentencer_T195 32950-33190 Sentence denotes Such genes are also automatically associated/tagged with the Gene Ontology term "innate immune response" in InnateDB, providing a more comprehensive list of such genes for use by the InnateDB Gene Ontology over-representation analysis tool.
TextSentencer_T196 33191-33273 Sentence denotes This is an on-going process but, to date, more than 500 genes have been annotated.
TextSentencer_T196 33191-33273 Sentence denotes This is an on-going process but, to date, more than 500 genes have been annotated.
TextSentencer_T197 33274-33462 Sentence denotes It is not intended for InnateDB to comprehensively annotate all of the roles of a given gene, but rather to provide a brief indication as to whether the gene has a role in innate immunity.
TextSentencer_T197 33274-33462 Sentence denotes It is not intended for InnateDB to comprehensively annotate all of the roles of a given gene, but rather to provide a brief indication as to whether the gene has a role in innate immunity.
TextSentencer_T198 33463-33610 Sentence denotes It has been suggested that curation of protein interaction datasets "can be error prone and possibly of lower quality than commonly assumed" [65] .
TextSentencer_T198 33463-33610 Sentence denotes It has been suggested that curation of protein interaction datasets "can be error prone and possibly of lower quality than commonly assumed" [65] .
TextSentencer_T199 33611-33769 Sentence denotes This assertion appears to be based largely on subjective reliability criteria such as the low overlap between curated datasets in various different databases.
TextSentencer_T199 33611-33769 Sentence denotes This assertion appears to be based largely on subjective reliability criteria such as the low overlap between curated datasets in various different databases.
TextSentencer_T200 33770-33934 Sentence denotes In response to this assertion, members of the IMEx consortium have pointed out that the low overlap between databases in this consortium is quite intentional [66] .
TextSentencer_T200 33770-33934 Sentence denotes In response to this assertion, members of the IMEx consortium have pointed out that the low overlap between databases in this consortium is quite intentional [66] .
TextSentencer_T201 33935-34029 Sentence denotes To avoid unnecessary redundancy, several of these databases coordinate their curation efforts.
TextSentencer_T201 33935-34029 Sentence denotes To avoid unnecessary redundancy, several of these databases coordinate their curation efforts.
TextSentencer_T202 34030-34218 Sentence denotes Furthermore, the IMEx consortium showed that curation error rates in their databases are in the region of 2-9% in comparison to the close to 50% error rate suggested by Cusick et al [65] .
TextSentencer_T202 34030-34218 Sentence denotes Furthermore, the IMEx consortium showed that curation error rates in their databases are in the region of 2-9% in comparison to the close to 50% error rate suggested by Cusick et al [65] .
TextSentencer_T203 34219-34497 Sentence denotes Similarly, the InnateDB curation team focuses on interactions that have not already been curated in any of the databases integrated into InnateDB, unless those interactions are supported by an additional un-reviewed article or there is additional annotation that could be added.
TextSentencer_T203 34219-34497 Sentence denotes Similarly, the InnateDB curation team focuses on interactions that have not already been curated in any of the databases integrated into InnateDB, unless those interactions are supported by an additional un-reviewed article or there is additional annotation that could be added.
TextSentencer_T204 34498-34666 Sentence denotes Therefore, the limited overlap between InnateDB and other databases is intentional, avoids redundancy and reflects the database's focus on innate immunity ( Figure 1 ).
TextSentencer_T204 34498-34666 Sentence denotes Therefore, the limited overlap between InnateDB and other databases is intentional, avoids redundancy and reflects the database's focus on innate immunity ( Figure 1 ).
TextSentencer_T205 34667-34808 Sentence denotes Consistent with the IMEx consortium curation process, InnateDB aims to accurately represent data on interactions presented in the literature.
TextSentencer_T205 34667-34808 Sentence denotes Consistent with the IMEx consortium curation process, InnateDB aims to accurately represent data on interactions presented in the literature.
TextSentencer_T206 34809-35081 Sentence denotes The curation team avoids, as much as possible, subjective calls on the quality of the evidence supporting an interaction unless that evidence is clearly insufficient to support the claims in the publication or does not support a direct physical or biochemical interaction.
TextSentencer_T206 34809-35081 Sentence denotes The curation team avoids, as much as possible, subjective calls on the quality of the evidence supporting an interaction unless that evidence is clearly insufficient to support the claims in the publication or does not support a direct physical or biochemical interaction.
TextSentencer_T207 35082-35246 Sentence denotes The process of experimentally verifying molecular interactions can offer many challenges in completing full MIMIx-compliant annotation for each InnateDB submission.
TextSentencer_T207 35082-35246 Sentence denotes The process of experimentally verifying molecular interactions can offer many challenges in completing full MIMIx-compliant annotation for each InnateDB submission.
TextSentencer_T208 35247-35414 Sentence denotes The absence of key information from publications often impedes the curation procedure, reducing the annotation available to accurately portray a molecular interaction.
TextSentencer_T208 35247-35414 Sentence denotes The absence of key information from publications often impedes the curation procedure, reducing the annotation available to accurately portray a molecular interaction.
TextSentencer_T209 35415-35588 Sentence denotes The incorrect or absent identification of the source organism of a participant molecule was recently reported as a common error in many external interaction databases [65] .
TextSentencer_T209 35415-35588 Sentence denotes The incorrect or absent identification of the source organism of a participant molecule was recently reported as a common error in many external interaction databases [65] .
TextSentencer_T210 35589-35736 Sentence denotes In particular, many publications describing molecular interactions do not clarify whether they are referring to a human or to a mouse gene/protein.
TextSentencer_T210 35589-35736 Sentence denotes In particular, many publications describing molecular interactions do not clarify whether they are referring to a human or to a mouse gene/protein.
TextSentencer_T211 35737-35986 Sentence denotes Over the approximately 90 million years that evolutionarily separate human and mouse [67] , there have been substantial changes to their respective signalling networks, and an interaction in one species does not guarantee it will occur in the other.
TextSentencer_T211 35737-35986 Sentence denotes Over the approximately 90 million years that evolutionarily separate human and mouse [67] , there have been substantial changes to their respective signalling networks, and an interaction in one species does not guarantee it will occur in the other.
TextSentencer_T212 35987-36074 Sentence denotes Databases like InnateDB, therefore, must distinguish between human and mouse molecules.
TextSentencer_T212 35987-36074 Sentence denotes Databases like InnateDB, therefore, must distinguish between human and mouse molecules.
TextSentencer_T213 36075-36248 Sentence denotes In many cases, information regarding the organism in question is reported in the supplemental data or in referenced material, requiring a great deal of effort to track down.
TextSentencer_T213 36075-36248 Sentence denotes In many cases, information regarding the organism in question is reported in the supplemental data or in referenced material, requiring a great deal of effort to track down.
TextSentencer_T214 36249-36382 Sentence denotes In a number of cases, direct correspondence with the authors is the only option available to the curators to verify such information.
TextSentencer_T214 36249-36382 Sentence denotes In a number of cases, direct correspondence with the authors is the only option available to the curators to verify such information.
TextSentencer_T215 36383-36439 Sentence denotes Thankfully, most authors are more than willing to reply.
TextSentencer_T215 36383-36439 Sentence denotes Thankfully, most authors are more than willing to reply.
TextSentencer_T216 36440-36508 Sentence denotes It is not uncommon, however, for authors to be themselves uncertain.
TextSentencer_T216 36440-36508 Sentence denotes It is not uncommon, however, for authors to be themselves uncertain.
TextSentencer_T217 36509-36623 Sentence denotes Journal editors and peer reviewers must be encouraged to ensure that such details are clearly specified in papers.
TextSentencer_T217 36509-36623 Sentence denotes Journal editors and peer reviewers must be encouraged to ensure that such details are clearly specified in papers.
TextSentencer_T218 36624-36766 Sentence denotes An important step in the right direction in this regard is the collaboration between the MINT database and the FEBS Letters journal [68, 69] .
TextSentencer_T218 36624-36766 Sentence denotes An important step in the right direction in this regard is the collaboration between the MINT database and the FEBS Letters journal [68, 69] .
TextSentencer_T219 36767-36966 Sentence denotes This collaboration involves the processing of accepted articles prior to publication by MINT curators to create a structured digital abstract, which describes the interactions in the paper in detail.
TextSentencer_T219 36767-36966 Sentence denotes This collaboration involves the processing of accepted articles prior to publication by MINT curators to create a structured digital abstract, which describes the interactions in the paper in detail.
TextSentencer_T220 36967-37036 Sentence denotes This process involves the manuscript authors in the curation process.
TextSentencer_T220 36967-37036 Sentence denotes This process involves the manuscript authors in the curation process.
TextSentencer_T221 37037-37216 Sentence denotes Another key challenge for curation is the fact that molecules can have several common names, which can lead to ambiguity in annotating the participant molecules in an interaction.
TextSentencer_T221 37037-37216 Sentence denotes Another key challenge for curation is the fact that molecules can have several common names, which can lead to ambiguity in annotating the participant molecules in an interaction.
TextSentencer_T222 37217-37317 Sentence denotes A prominent example in the innate immunity area is the gene encoding the TLR adaptor protein, TIRAP.
TextSentencer_T222 37217-37317 Sentence denotes A prominent example in the innate immunity area is the gene encoding the TLR adaptor protein, TIRAP.
TextSentencer_T223 37318-37360 Sentence denotes This gene is also frequently known as MAL.
TextSentencer_T223 37318-37360 Sentence denotes This gene is also frequently known as MAL.
TextSentencer_T224 37361-37489 Sentence denotes The official HGNC name [63] for this gene is TIRAP, however, there is another completely different gene with the HGNC name, MAL.
TextSentencer_T224 37361-37489 Sentence denotes The official HGNC name [63] for this gene is TIRAP, however, there is another completely different gene with the HGNC name, MAL.
TextSentencer_T225 37490-37530 Sentence denotes One can see the potential for confusion.
TextSentencer_T225 37490-37530 Sentence denotes One can see the potential for confusion.
TextSentencer_T226 37531-37706 Sentence denotes If provided in the paper, the curators use gene/protein accession numbers to confirm the gene in question -this should be strongly encouraged by journal editors and reviewers.
TextSentencer_T226 37531-37706 Sentence denotes If provided in the paper, the curators use gene/protein accession numbers to confirm the gene in question -this should be strongly encouraged by journal editors and reviewers.
TextSentencer_T227 37707-37865 Sentence denotes As discussed above, the curation system also displays all synonyms, full-names and other details for a curator to view when annotating a participant molecule.
TextSentencer_T227 37707-37865 Sentence denotes As discussed above, the curation system also displays all synonyms, full-names and other details for a curator to view when annotating a participant molecule.
TextSentencer_T228 37866-38027 Sentence denotes This approach highlights cases where there are two or more genes with similar/same names, allowing curators to review carefully which gene they are referring to.
TextSentencer_T228 37866-38027 Sentence denotes This approach highlights cases where there are two or more genes with similar/same names, allowing curators to review carefully which gene they are referring to.
TextSentencer_T229 38028-38126 Sentence denotes Another related issue is identifying which specific protein isoform is described in an experiment.
TextSentencer_T229 38028-38126 Sentence denotes Another related issue is identifying which specific protein isoform is described in an experiment.
TextSentencer_T230 38127-38172 Sentence denotes At present, this is often impossible to tell.
TextSentencer_T230 38127-38172 Sentence denotes At present, this is often impossible to tell.
TextSentencer_T231 38173-38314 Sentence denotes Therefore, all interactions in Inna-teDB are mapped back to the parent gene ID, with annotation on the molecule type (e.g. protein) involved.
TextSentencer_T231 38173-38314 Sentence denotes Therefore, all interactions in Inna-teDB are mapped back to the parent gene ID, with annotation on the molecule type (e.g. protein) involved.
TextSentencer_T232 38315-38371 Sentence denotes Other challenges to curation include evolving standards.
TextSentencer_T232 38315-38371 Sentence denotes Other challenges to curation include evolving standards.
TextSentencer_T233 38372-38561 Sentence denotes PSI-MI [59] and OBO terms [60] , describing interaction types, detection methods, cell-types, etc, are not static and a term that is valid today may be deprecated or replaced in the future.
TextSentencer_T233 38372-38561 Sentence denotes PSI-MI [59] and OBO terms [60] , describing interaction types, detection methods, cell-types, etc, are not static and a term that is valid today may be deprecated or replaced in the future.
TextSentencer_T234 38562-38704 Sentence denotes Similarly, not all relevant terms have been described in ontologies yet; new interaction detection methods, for example, may not be specified.
TextSentencer_T234 38562-38704 Sentence denotes Similarly, not all relevant terms have been described in ontologies yet; new interaction detection methods, for example, may not be specified.
TextSentencer_T235 38705-38763 Sentence denotes Additionally, not all fields have standardised ontologies.
TextSentencer_T235 38705-38763 Sentence denotes Additionally, not all fields have standardised ontologies.
TextSentencer_T236 38764-38829 Sentence denotes Cell lines, for example, do not have a standardised OBO ontology.
TextSentencer_T236 38764-38829 Sentence denotes Cell lines, for example, do not have a standardised OBO ontology.
TextSentencer_T237 38830-38995 Sentence denotes InnateDB adheres to using cell line names from the American Type Culture Collection (http://www.atcc.org) where possible, however, this listing is not comprehensive.
TextSentencer_T237 38830-38995 Sentence denotes InnateDB adheres to using cell line names from the American Type Culture Collection (http://www.atcc.org) where possible, however, this listing is not comprehensive.
TextSentencer_T238 38996-39118 Sentence denotes An additional issue regarding cell lines include cases where different cell lines may have the same or very similar names.
TextSentencer_T238 38996-39118 Sentence denotes An additional issue regarding cell lines include cases where different cell lines may have the same or very similar names.
TextSentencer_T239 39119-39382 Sentence denotes While these and other issues provide notable challenges to the curation team, the InnateDB curation system, its detailed guide on the curation process, and regular meetings to discuss potential pitfalls, ensures that InnateDB has a very high standard of curation.
TextSentencer_T239 39119-39382 Sentence denotes While these and other issues provide notable challenges to the curation team, the InnateDB curation system, its detailed guide on the curation process, and regular meetings to discuss potential pitfalls, ensures that InnateDB has a very high standard of curation.
TextSentencer_T240 39383-39729 Sentence denotes As discussed, InnateDB curation of innate immunity relevant interactions, pathways and genes is providing the most comprehensive picture yet of the innate immune interactome, and promises to shed new light into its regulation and how pathogens can evolve to subvert it. been integrated into InnateDB for freely providing their data to the public.
TextSentencer_T240 39383-39729 Sentence denotes As discussed, InnateDB curation of innate immunity relevant interactions, pathways and genes is providing the most comprehensive picture yet of the innate immune interactome, and promises to shed new light into its regulation and how pathogens can evolve to subvert it. been integrated into InnateDB for freely providing their data to the public.
TextSentencer_T241 39730-39869 Sentence denotes Grateful thanks also go to the many researchers who have taken the time to respond to our queries regarding curation of their publications.
TextSentencer_T241 39730-39869 Sentence denotes Grateful thanks also go to the many researchers who have taken the time to respond to our queries regarding curation of their publications.
TextSentencer_T242 39870-40036 Sentence denotes Authors' contributions DJL wrote the paper, with input from other authors, oversees the curation effort with REWH and FSLB, and carried out the analyses in the paper.
TextSentencer_T242 39870-40036 Sentence denotes Authors' contributions DJL wrote the paper, with input from other authors, oversees the curation effort with REWH and FSLB, and carried out the analyses in the paper.
TextSentencer_T243 40037-40101 Sentence denotes CC designed the InnateDB curation software, with input from DJL.
TextSentencer_T243 40037-40101 Sentence denotes CC designed the InnateDB curation software, with input from DJL.
TextSentencer_T244 40102-40175 Sentence denotes MN, MY, RL, AS, GR, KW and JQ all have worked as curators on the project.
TextSentencer_T244 40102-40175 Sentence denotes MN, MY, RL, AS, GR, KW and JQ all have worked as curators on the project.
TextSentencer_T245 40176-40244 Sentence denotes GLW, MRL, KB, AKF are database and software developers for InnateDB.
TextSentencer_T245 40176-40244 Sentence denotes GLW, MRL, KB, AKF are database and software developers for InnateDB.
TextSentencer_T246 40245-40285 Sentence denotes All authors read and approved the paper.
TextSentencer_T246 40245-40285 Sentence denotes All authors read and approved the paper.