کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2039865 1073086 2015 14 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Systematic Discovery of Human Gene Function and Principles of Modular Organization through Phylogenetic Profiling
ترجمه فارسی عنوان
کشف سیستماتیک تابع ژن انسان و اصول سازمان مدولار از طریق تالیف فیلوژنتیک
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم کشاورزی و بیولوژیک علوم کشاورزی و بیولوژیک (عمومی)
چکیده انگلیسی


• Correlated evolutionary histories predict functions for human genes
• Reconstructing shared ancestry extends predictive ability to gene families
• Scalable scoring metric leads to unbiased genome-wide functional predictions
• Predictions are experimentally tractable, and a subset was validated in cell lines

SummaryFunctional links between genes can be predicted using phylogenetic profiling, by correlating the appearance and loss of homologs in subsets of species. However, effective genome-wide phylogenetic profiling has been hindered by the large fraction of human genes related to each other through historical duplication events. Here, we overcame this challenge by automatically profiling over 30,000 groups of homologous human genes (orthogroups) representing the entire protein-coding genome across 177 eukaryotic species (hOP profiles). By generating a full pairwise orthogroup phylogenetic co-occurrence matrix, we derive unbiased genome-wide predictions of functional modules (hOP modules). Our approach predicts functions for hundreds of poorly characterized genes. The results suggest evolutionary constraints that lead components of protein complexes and metabolic pathways to co-evolve while genes in signaling and transcriptional networks do not. As a proof of principle, we validated two subsets of candidates experimentally for their predicted link to the actin-nucleating WASH complex and cilia/basal body function.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: - Volume 10, Issue 6, 17 February 2015, Pages 993–1006
نویسندگان
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