Mocap: large-scale inference of transcription factor binding sites from chromatin accessibility.
Differential binding of transcription factors (TFs) at cis-regulatory loci drives the differentiation and function of diverse cellular lineages. Understanding the regulatory interactions that underlie cell fate decisions requires characterizing TF binding sites (TFBS) across multiple cell types and conditions. Techniques, e.g. ChIP-Seq can reveal genome-wide patterns of TF binding, but typically requires laborious and costly experiments for each TF-cell-type (TFCT) condition of interest. Chromosomal accessibility assays can connect accessible chromatin in one cell type to many TFs through sequence motif mapping. Such methods, however, rarely take into account that the genomic context preferred by each factor differs from TF to TF, and from cell type to cell type. To address the differences in TF behaviors, we developed Mocap, a method that integrates chromatin accessibility, motif scores, TF footprints, CpG/GC content, evolutionary conservation and other factors in an ensemble of TFCT-specific classifiers. We show that integration of genomic features, such as CpG islands improves TFBS prediction in some TFCT. Further, we describe a method for mapping new TFCT, for which no ChIP-seq data exists, onto our ensemble of classifiers and show that our cross-sample TFBS prediction method outperforms several previously described methods.
Department of Biology, New York University, New York, NY 10003, USA.
Xi
X
Chen
Department of Computer Science, New York University, New York, NY 10003, USA.
Bowen
B
Yu
Center for Computational Biology, Flatiron Foundation, Simons Foundation, New York, NY 10010, USA.
Nicholas
N
Carriero
Department of Computer Science, New York University, New York, NY 10003, USA.
Claudio
C
Silva
Department of Biology, New York University, New York, NY 10003, USA.|Department of Computer Science, New York University, New York, NY 10003, USA.|Center for Computational Biology, Flatiron Foundation, Simons Foundation, New York, NY 10010, USA.
Richard
R
Bonneau
D001482:Base Composition; D001665:Binding Sites; D002460:Cell Line; D002843:Chromatin / Q000737:chemistry / Q000378:metabolism*; D047369:Chromatin Immunoprecipitation; D018899:CpG Islands; D030541:Databases, Genetic; D004475:Ectoderm / Q000166:cytology / Q000378:metabolism*; D004707:Endoderm / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D008648:Mesoderm / Q000166:cytology / Q000378:metabolism*; D059372:Nucleotide Motifs; D009928:Organ Specificity; D011485:Protein Binding; D012984:Software; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
D002843:Chromatin; D014157:Transcription Factors