PMC:4156421 / 4250-7136 JSONTXT

{"project":"2_test","denotations":[{"id":"25192356-21478889-90446710","span":{"begin":919,"end":921},"obj":"21478889"},{"id":"25192356-20644199-90446711","span":{"begin":924,"end":926},"obj":"20644199"},{"id":"25192356-19684571-90446712","span":{"begin":971,"end":973},"obj":"19684571"},{"id":"25192356-24487276-90446713","span":{"begin":1505,"end":1507},"obj":"24487276"},{"id":"25192356-18974171-90446714","span":{"begin":1669,"end":1671},"obj":"18974171"},{"id":"25192356-24487276-90446715","span":{"begin":1928,"end":1930},"obj":"24487276"}],"text":"Materials and Methods\n\nEthics\nWritten informed consent for body donation for research and education was obtained through the University of Washington School of Medicine Willed Body Program. All research was conducting according to Declaration of Helsinki principles.\n\nGenome sequencing\nTissue samples were obtained postmortem from the unembalmed cadaver. A cube of liver tissue approximately 1 cm on a side was dissected from the liver and frozen at −80°C to be used in the preparation of DNA for sequencing. 17 µg of genomic DNA was extracted using Qiagen DNeasy Blood \u0026 Tissue Kit from this sample. Shotgun sequencing libraries were prepared using the KAPA library preparation kit (Kapa Biosystems) following manufacturer's instructions. DNA was sequenced on an Illumina HiSeq 2000 with paired-end 100 bp reads. The raw sequence data was mapped to hg19/GRCh37 and variants were called with GATK using best practices [17]–[19]. Variants were annotated using SeattleSeq [20]. Allele frequencies for the European-American population were derived from the University of Washington Genome Variation Server (http://gvs.gs.washington.edu). Findings discussed in the manuscript were manually evaluated by verifying read data using the Integrative Genomics Viewer (IGV, http://www.broadinstitute.org/igv/).\n\nAnalysis of variants in the vicinity of rs35705950 (MUC5B)\nTo assess the possibility of causal variants underlying the MUC5B GWAS signal in LD with rs35705950, we used the recently described CADD method [21] to generate “C-scores” for each of the patient's variants within 1 Mb of rs35705950 (Chr11∶1,241,221). LD data from the SNP Annotation and Proxy Search (SNAP) [22] did not identify any variants in the CEU population in high LD (r-squared \u003e0.6) with rs35705950 within 1 Mb. Nonetheless, we ranked variants by C-scores, which are an integrated measure of “deleteriousness” outputted on a “phred-like” scale from 0 to 99 [21]. We additionally investigated a region within 20 kB of rs35705950 to identify any rare (AF\u003c2%) variants that overlapped with DNase hypersensitive or putative transcription factor binding sites.\n\nDidactics\nA group of 15 first year medical students, including 12 combined M.D./Ph.D. students from the Medical Scientist Training Program (MSTP), plus a more senior MSTP student (AK) who functioned as a teaching assistant, met in the Human Anatomy Lab and classroom for a total of 8 hours dispersed through 5 sessions. In smaller groups, the students, under the supervision of the teaching assistant, prepared DNA samples for genomic sequencing. Students were then paired off to complete remaining bioinformatic analysis and jointly draft the manuscript using a shared document online over the ensuing academic quarter. Instructors and students met as a group in 3 additional sessions spanning a total of 5 hours in order to refine and revise the manuscript."}

{"project":"PubTator4TogoVar","denotations":[{"id":"27478","span":{"begin":1449,"end":1459},"obj":"SNP"},{"id":"27480","span":{"begin":1758,"end":1768},"obj":"SNP"},{"id":"27481","span":{"begin":1582,"end":1592},"obj":"SNP"},{"id":"27482","span":{"begin":1987,"end":1997},"obj":"SNP"},{"id":"27476","span":{"begin":1341,"end":1351},"obj":"SNP"},{"id":"27660","span":{"begin":1341,"end":1351},"obj":"SNP"}],"attributes":[{"id":"A27478","pred":"resolved_to","subj":"27478","obj":"tmVar:rs35705950;VariantGroup:27;RS#:35705950"},{"id":"A27480","pred":"resolved_to","subj":"27480","obj":"tmVar:rs35705950;VariantGroup:27;RS#:35705950"},{"id":"A27481","pred":"resolved_to","subj":"27481","obj":"tmVar:rs35705950;VariantGroup:27;RS#:35705950"},{"id":"A27482","pred":"resolved_to","subj":"27482","obj":"tmVar:rs35705950;VariantGroup:27;RS#:35705950"},{"id":"A27476","pred":"resolved_to","subj":"27476","obj":"tmVar:rs35705950;VariantGroup:27;RS#:35705950"},{"id":"A27660","pred":"resolved_to","subj":"27660","obj":"tmVar:rs35705950;VariantGroup:27;RS#:35705950"}],"text":"Materials and Methods\n\nEthics\nWritten informed consent for body donation for research and education was obtained through the University of Washington School of Medicine Willed Body Program. All research was conducting according to Declaration of Helsinki principles.\n\nGenome sequencing\nTissue samples were obtained postmortem from the unembalmed cadaver. A cube of liver tissue approximately 1 cm on a side was dissected from the liver and frozen at −80°C to be used in the preparation of DNA for sequencing. 17 µg of genomic DNA was extracted using Qiagen DNeasy Blood \u0026 Tissue Kit from this sample. Shotgun sequencing libraries were prepared using the KAPA library preparation kit (Kapa Biosystems) following manufacturer's instructions. DNA was sequenced on an Illumina HiSeq 2000 with paired-end 100 bp reads. The raw sequence data was mapped to hg19/GRCh37 and variants were called with GATK using best practices [17]–[19]. Variants were annotated using SeattleSeq [20]. Allele frequencies for the European-American population were derived from the University of Washington Genome Variation Server (http://gvs.gs.washington.edu). Findings discussed in the manuscript were manually evaluated by verifying read data using the Integrative Genomics Viewer (IGV, http://www.broadinstitute.org/igv/).\n\nAnalysis of variants in the vicinity of rs35705950 (MUC5B)\nTo assess the possibility of causal variants underlying the MUC5B GWAS signal in LD with rs35705950, we used the recently described CADD method [21] to generate “C-scores” for each of the patient's variants within 1 Mb of rs35705950 (Chr11∶1,241,221). LD data from the SNP Annotation and Proxy Search (SNAP) [22] did not identify any variants in the CEU population in high LD (r-squared \u003e0.6) with rs35705950 within 1 Mb. Nonetheless, we ranked variants by C-scores, which are an integrated measure of “deleteriousness” outputted on a “phred-like” scale from 0 to 99 [21]. We additionally investigated a region within 20 kB of rs35705950 to identify any rare (AF\u003c2%) variants that overlapped with DNase hypersensitive or putative transcription factor binding sites.\n\nDidactics\nA group of 15 first year medical students, including 12 combined M.D./Ph.D. students from the Medical Scientist Training Program (MSTP), plus a more senior MSTP student (AK) who functioned as a teaching assistant, met in the Human Anatomy Lab and classroom for a total of 8 hours dispersed through 5 sessions. In smaller groups, the students, under the supervision of the teaching assistant, prepared DNA samples for genomic sequencing. Students were then paired off to complete remaining bioinformatic analysis and jointly draft the manuscript using a shared document online over the ensuing academic quarter. Instructors and students met as a group in 3 additional sessions spanning a total of 5 hours in order to refine and revise the manuscript."}

{"project":"PubTatorOnTogoVar","denotations":[{"id":"27476","span":{"begin":1341,"end":1351},"obj":"SNP"},{"id":"27478","span":{"begin":1449,"end":1459},"obj":"SNP"},{"id":"27480","span":{"begin":1758,"end":1768},"obj":"SNP"},{"id":"27481","span":{"begin":1582,"end":1592},"obj":"SNP"},{"id":"27482","span":{"begin":1987,"end":1997},"obj":"SNP"},{"id":"27660","span":{"begin":1341,"end":1351},"obj":"SNP"},{"id":"T1","span":{"begin":1341,"end":1351},"obj":"SNP"},{"id":"T1","span":{"begin":1449,"end":1459},"obj":"SNP"},{"id":"T2","span":{"begin":1758,"end":1768},"obj":"SNP"},{"id":"T3","span":{"begin":1582,"end":1592},"obj":"SNP"},{"id":"T4","span":{"begin":1987,"end":1997},"obj":"SNP"},{"id":"T1","span":{"begin":1341,"end":1351},"obj":"SNP"}],"attributes":[{"id":"A27476","pred":"resolved_to","subj":"27476","obj":"tmVar:rs35705950;VariantGroup:27;RS#:35705950"},{"id":"A27478","pred":"resolved_to","subj":"27478","obj":"tmVar:rs35705950;VariantGroup:27;RS#:35705950"},{"id":"A27480","pred":"resolved_to","subj":"27480","obj":"tmVar:rs35705950;VariantGroup:27;RS#:35705950"},{"id":"A27481","pred":"resolved_to","subj":"27481","obj":"tmVar:rs35705950;VariantGroup:27;RS#:35705950"},{"id":"A27482","pred":"resolved_to","subj":"27482","obj":"tmVar:rs35705950;VariantGroup:27;RS#:35705950"},{"id":"A27660","pred":"resolved_to","subj":"27660","obj":"tmVar:rs35705950;VariantGroup:27;RS#:35705950"}],"text":"Materials and Methods\n\nEthics\nWritten informed consent for body donation for research and education was obtained through the University of Washington School of Medicine Willed Body Program. All research was conducting according to Declaration of Helsinki principles.\n\nGenome sequencing\nTissue samples were obtained postmortem from the unembalmed cadaver. A cube of liver tissue approximately 1 cm on a side was dissected from the liver and frozen at −80°C to be used in the preparation of DNA for sequencing. 17 µg of genomic DNA was extracted using Qiagen DNeasy Blood \u0026 Tissue Kit from this sample. Shotgun sequencing libraries were prepared using the KAPA library preparation kit (Kapa Biosystems) following manufacturer's instructions. DNA was sequenced on an Illumina HiSeq 2000 with paired-end 100 bp reads. The raw sequence data was mapped to hg19/GRCh37 and variants were called with GATK using best practices [17]–[19]. Variants were annotated using SeattleSeq [20]. Allele frequencies for the European-American population were derived from the University of Washington Genome Variation Server (http://gvs.gs.washington.edu). Findings discussed in the manuscript were manually evaluated by verifying read data using the Integrative Genomics Viewer (IGV, http://www.broadinstitute.org/igv/).\n\nAnalysis of variants in the vicinity of rs35705950 (MUC5B)\nTo assess the possibility of causal variants underlying the MUC5B GWAS signal in LD with rs35705950, we used the recently described CADD method [21] to generate “C-scores” for each of the patient's variants within 1 Mb of rs35705950 (Chr11∶1,241,221). LD data from the SNP Annotation and Proxy Search (SNAP) [22] did not identify any variants in the CEU population in high LD (r-squared \u003e0.6) with rs35705950 within 1 Mb. Nonetheless, we ranked variants by C-scores, which are an integrated measure of “deleteriousness” outputted on a “phred-like” scale from 0 to 99 [21]. We additionally investigated a region within 20 kB of rs35705950 to identify any rare (AF\u003c2%) variants that overlapped with DNase hypersensitive or putative transcription factor binding sites.\n\nDidactics\nA group of 15 first year medical students, including 12 combined M.D./Ph.D. students from the Medical Scientist Training Program (MSTP), plus a more senior MSTP student (AK) who functioned as a teaching assistant, met in the Human Anatomy Lab and classroom for a total of 8 hours dispersed through 5 sessions. In smaller groups, the students, under the supervision of the teaching assistant, prepared DNA samples for genomic sequencing. Students were then paired off to complete remaining bioinformatic analysis and jointly draft the manuscript using a shared document online over the ensuing academic quarter. Instructors and students met as a group in 3 additional sessions spanning a total of 5 hours in order to refine and revise the manuscript."}