PMC:6610382 / 7387-8521
Annnotations
{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/6610382","sourcedb":"PMC","sourceid":"6610382","source_url":"https://www.ncbi.nlm.nih.gov/pmc/6610382","text":"A more general challenge for employing CRAFT for target identification is in distinguishing the mechanism of disease from the body’s response to it. In the case of TLE, limiting seizures is an end in and of itself that may curb disease progression.7 It is much less obvious that this paradigm can distinguish between homeostatic and pathologic changes in transcription in other diseases. Perhaps a more challenging limitation for CRAFT is its reliance on models of how surface receptor activity translates into changes in transcription. Many neurological diseases feature mutations in proteins as a key pathological mechanism that could invalidate models for predicting transcriptional responses to receptor activation. Trinucleotide repeat disorders such as spinocerebellar ataxia type I often feature “gain-of-function” mutant proteins that affect a wide variety of cellular processes and whose transcriptional networks may be harder to model.8 As a result, while CRAFT represents an exciting new opportunity for epilepsy drug discovery, there is more work to be done in order to generalize the method across neurological disorders.","tracks":[{"project":"0_colil","denotations":[{"id":"31035818-3816713-4168","span":{"begin":248,"end":249},"obj":"3816713"},{"id":"31035818-17417937-4169","span":{"begin":945,"end":946},"obj":"17417937"}],"attributes":[{"subj":"31035818-3816713-4168","pred":"source","obj":"0_colil"},{"subj":"31035818-17417937-4169","pred":"source","obj":"0_colil"}]},{"project":"2_test","denotations":[{"id":"31035818-3816713-28641017","span":{"begin":248,"end":249},"obj":"3816713"},{"id":"31035818-17417937-28641018","span":{"begin":945,"end":946},"obj":"17417937"}],"attributes":[{"subj":"31035818-3816713-28641017","pred":"source","obj":"2_test"},{"subj":"31035818-17417937-28641018","pred":"source","obj":"2_test"}]},{"project":"MyTest","denotations":[{"id":"31035818-3816713-28641017","span":{"begin":248,"end":250},"obj":"3816713"},{"id":"31035818-17417937-28641018","span":{"begin":945,"end":947},"obj":"17417937"}],"namespaces":[{"prefix":"_base","uri":"https://www.uniprot.org/uniprot/testbase"},{"prefix":"UniProtKB","uri":"https://www.uniprot.org/uniprot/"},{"prefix":"uniprot","uri":"https://www.uniprot.org/uniprotkb/"}],"attributes":[{"subj":"31035818-3816713-28641017","pred":"source","obj":"MyTest"},{"subj":"31035818-17417937-28641018","pred":"source","obj":"MyTest"}]},{"project":"testtesttest","denotations":[{"id":"T27","span":{"begin":469,"end":476},"obj":"Body_part"},{"id":"T28","span":{"begin":868,"end":886},"obj":"Body_part"}],"attributes":[{"id":"A27","pred":"uberon_id","subj":"T27","obj":"http://purl.obolibrary.org/obo/UBERON_0002416"},{"id":"A28","pred":"uberon_id","subj":"T28","obj":"http://purl.obolibrary.org/obo/GO_0042995"},{"subj":"T27","pred":"source","obj":"testtesttest"},{"subj":"T28","pred":"source","obj":"testtesttest"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"0_colil","color":"#ecc893","default":true},{"id":"2_test","color":"#ae93ec"},{"id":"MyTest","color":"#93ec94"},{"id":"testtesttest","color":"#ec93ab"}]}]}}