Allegro: analyzing expression and sequence in concert to discover regulatory programs.
A major goal of system biology is the characterization of transcription factors and microRNAs (miRNAs) and the transcriptional programs they regulate. We present Allegro, a method for de-novo discovery of cis-regulatory transcriptional programs through joint analysis of genome-wide expression data and promoter or 3' UTR sequences. The algorithm uses a novel log-likelihood-based, non-parametric model to describe the expression pattern shared by a group of co-regulated genes. We show that Allegro is more accurate and sensitive than existing techniques, and can simultaneously analyze multiple expression datasets with more than 100 conditions. We apply Allegro on datasets from several species and report on the transcriptional modules it uncovers. Our analysis reveals a novel motif over-represented in the promoters of genes highly expressed in murine oocytes, and several new motifs related to fly development. Finally, using stem-cell expression profiles, we identify three miRNA families with pivotal roles in human embryogenesis.
Halperin
Yonit
Y
School of Computer Science, Tel Aviv University, Tel Aviv 69978, Israel.
Linhart
Chaim
C
Ulitsky
Igor
I
Shamir
Ron
R
D020413:3' Untranslated Regions / Q000737:chemistry*; D000465:Algorithms; D000818:Animals; D002453:Cell Cycle / Q000235:genetics; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D017422:Sequence Analysis, DNA; D017423:Sequence Analysis, RNA; D012984:Software; D013234:Stem Cells / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
D020413:3' Untranslated Regions; D035683:MicroRNAs; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; C088589:HOG1 protein, S cerevisiae; D020928:Mitogen-Activated Protein Kinases