PMC:2041973 / 46914-50396 JSONTXT

{"target":"http://pubannotation.org/docs/sourcedb/PMC/sourceid/2041973","sourcedb":"PMC","sourceid":"2041973","source_url":"http://www.ncbi.nlm.nih.gov/pmc/2041973","text":"Functional and Expression Characteristics of REAP[+] Genes\nIn total, 1,500 genes were identified that contained 1,737 REAP[+] exons, 68% of which lacked prior transcript (EST/cDNA) evidence for AS. To determine whether genes that contained REAP[+] exons, which we refer to as REAP[+] genes, are biased toward particular biological activities, REAP[+] genes were compared to a set of REAP analyzed genes not found to have REAP[+] exons (REAP[−] genes). A Gene Ontology analysis revealed that REAP[+] genes are enriched for GO molecular function categories “ATP binding,” “helicase activity,” “protein serine/theronine kinase activity,” “small GTPase regulatory/interacting protein activity,” and “thyroid hormone receptor binding” (Table 1). In terms of GO biological process categories, REAP[+] genes were more frequently involved in “ubiquitin cycle.” Similar results were obtained when we compared REAP[+] genes to all human genes that did not contain REAP[+] exons (Table 1) [55].\nTable 1 Significantly Enriched Gene Ontology Terms in REAP[+] Genes (Cutoff of Two Significant “Outliers” per Probeset) Next we asked if REAP[+] genes are differentially expressed in hESCs compared to NPs and vice versa. For this analysis, the t-statistics computed above measuring the enrichment of a gene in hESCs relative to NPs was utilized for only REAP-analyzed genes. At a defined absolute-valued cutoff, genes were divided into three categories: “enriched in hESCs,” “enriched in NP,” or “unchanged” (Figure 8A). Increasing the t-statistic cutoff from one to five, the fraction of REAP[+] genes relative to REAP-analyzed genes remained constant in the “unchanged” categories (Figure 8B). However, the fraction of REAP[+] exons decreased significantly in “enriched in hESCs” and “enriched in NPs” categories. If we increased the cutoffs on genes that were randomly assigned as REAP[+] and REAP[−], controlling for the same number of genes in each category, we observed that the fraction of REAP[+] exons remained unchanged for all three categories (Figure 8C). To illustrate, at a cutoff of five, 10% (29 of 267) of enriched NP genes were REAP[+] genes and 8.8% (102 of 1,162) of enriched hESC genes were REAP[+], significantly different (p \u003c 0.000005) from the random control where ∼14% of enriched NP and enriched hESC genes were REAP[+]. At a cutoff of five, 14% (1,368 of 9,636) of genes that were expressed at similar levels between hESCs and NPs were REAP[+]. Our results suggested that a strategy of focusing on differentially expressed genes would miss at least 14% of transcriptionally unchanged genes that may nevertheless have functional AS differences between hESCs and NPs.\nFigure 8 Analysis of REAP[+] Genes Relative to Transcriptional Differences\n(A) Histogam of t-statistics computed from gene-level signal estimates measuring the enrichment of genes in hESC and in NP. Genes on the right of the vertical line at 5 were designated enriched in hESC and genes on the left of the vertical line at −5 were designated enriched in NP; genes in between −5 and 5 were designated as “unchanged” or expressed similarly in hESC and NP.\n(B) Vertical bars representing the percentage of REAP[+] genes out of all genes in the different classifications (dashed bar: “enriched in hESC”; black filled bar: “unchanged”; white filled bar: “enriched in NP”), at different cutoffs of 1 to 5.\n(C) Set of genes where REAP[+] designation was randomly chosen. Similar representation as in (B).\n\nC","divisions":[{"label":"Title","span":{"begin":0,"end":58}},{"label":"Table caption","span":{"begin":984,"end":1106}},{"label":"Figure caption","span":{"begin":2681,"end":3481}},{"label":"Title","span":{"begin":2691,"end":2756}}],"tracks":[{"project":"2_test","denotations":[{"id":"17967047-15708978-85283467","span":{"begin":979,"end":981},"obj":"15708978"},{"id":"T87826","span":{"begin":979,"end":981},"obj":"15708978"}],"attributes":[{"subj":"17967047-15708978-85283467","pred":"source","obj":"2_test"},{"subj":"T87826","pred":"source","obj":"2_test"}]},{"project":"CellFinder","denotations":[{"id":"T66","span":{"begin":835,"end":844},"obj":"GeneProtein"},{"id":"T67","span":{"begin":1188,"end":1191},"obj":"CellType"},{"id":"T68","span":{"begin":1315,"end":1318},"obj":"CellType"},{"id":"T69","span":{"begin":2442,"end":2445},"obj":"CellType"},{"id":"T70","span":{"begin":696,"end":720},"obj":"GeneProtein"},{"id":"T71","span":{"begin":636,"end":679},"obj":"GeneProtein"},{"id":"T72","span":{"begin":571,"end":579},"obj":"GeneProtein"},{"id":"T73","span":{"begin":1297,"end":1302},"obj":"CellType"},{"id":"T74","span":{"begin":1170,"end":1175},"obj":"CellType"},{"id":"T75","span":{"begin":1454,"end":1459},"obj":"CellType"},{"id":"T76","span":{"begin":921,"end":926},"obj":"Species"},{"id":"T77","span":{"begin":2432,"end":2437},"obj":"CellType"},{"id":"T78","span":{"begin":1786,"end":1789},"obj":"CellType"},{"id":"T79","span":{"begin":1762,"end":1767},"obj":"CellType"},{"id":"T80","span":{"begin":2666,"end":2671},"obj":"CellType"},{"id":"T81","span":{"begin":2676,"end":2679},"obj":"CellType"}],"attributes":[{"subj":"T66","pred":"source","obj":"CellFinder"},{"subj":"T67","pred":"source","obj":"CellFinder"},{"subj":"T68","pred":"source","obj":"CellFinder"},{"subj":"T69","pred":"source","obj":"CellFinder"},{"subj":"T70","pred":"source","obj":"CellFinder"},{"subj":"T71","pred":"source","obj":"CellFinder"},{"subj":"T72","pred":"source","obj":"CellFinder"},{"subj":"T73","pred":"source","obj":"CellFinder"},{"subj":"T74","pred":"source","obj":"CellFinder"},{"subj":"T75","pred":"source","obj":"CellFinder"},{"subj":"T76","pred":"source","obj":"CellFinder"},{"subj":"T77","pred":"source","obj":"CellFinder"},{"subj":"T78","pred":"source","obj":"CellFinder"},{"subj":"T79","pred":"source","obj":"CellFinder"},{"subj":"T80","pred":"source","obj":"CellFinder"},{"subj":"T81","pred":"source","obj":"CellFinder"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"2_test","color":"#ec93b8","default":true},{"id":"CellFinder","color":"#93d2ec"}]}]}}