CisBP data

Matthew T. Weirauch^1,2*, Ally Yang^2,*, Mihai Albu², Atina Cote², Alejandro Montenegro-Montero³, Philipp Drewe⁴, Hamed S. Najafabadi², Samuel A. Lambert⁵, Ishminder Mann², Kate Cook⁵, Hong Zheng², Alejandra Goity³, Harm van Bakel⁶, Jean-Claude Lozano⁷, Mary Galli⁸, Mathew Lewsey^8,9, Eryong Huang¹⁰, Tuhin Mukherjee¹¹, Xiaoting Chen¹¹, John S. Reece-Hoyes¹², Sridhar Govindarajan¹³, Gad Shaulsky¹⁰, Albertha J.M. Walhout¹², François-Yves Bouget⁷, Gunnar Ratsch⁴, Luis F. Larrondo³, Joseph R. Ecker^8,9,14, Timothy R. Hughes^2,5#

¹ Center for Autoimmune Genomics and Etiology (CAGE) and Divisions of Rheumatology and Biomedical Informatics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA
² Banting and Best Department of Medical Research, University of Toronto, Toronto, ON, Canada
³ Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile
⁴ Computational Biology Center, Sloan-Kettering Institute, New York, NY, USA
⁵ Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada
⁶ Icahn Institute for Genomics and Multiscale Biology, Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York City, NY, USA
⁷ Université Pierre et Marie Curie, CNRS, UMR 7621, Observatoire Océanologique de Banyuls sur Mer, France
⁸ Genomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, CA, USA
⁹ Plant Biology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA, USA
¹⁰ Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA
¹¹ School of Electronic and Computing Systems, University of Cincinnati, Cincinnati, OH, USA
¹² Program in Systems Biology, University of Massachusetts Medical School, Worcester, MA, USA
¹³ DNA2.0 Inc, Menlo Park, CA, USA
¹⁴ Howard Hughes Medical Institute, The Salk Institute for Biological Studies, La Jolla, CA, USA

^*these authors contributed equally

^#To whom correspondance should be addressed:

Abstract

Transcription factor (TF) DNA sequence preferences direct their regulatory activity, but are currently known for only ~1% of all eukaryotic TFs. Broadly sampling DNA-binding domain (DBD) types from multiple eukaryotic clades, we determined DNA sequence preferences for >1,000 TFs encompassing 54 different DBD classes from 131 diverse eukaryotes. We find that closely related DBDs almost always have very similar DNA sequence preferences, enabling inference of motifs for ~34% of the ~170,000 known or predicted eukaryotic TFs. Sequences matching both measured and inferred motifs are enriched in ChIP-seq peaks and upstream of transcription start sites in diverse eukaryotic lineages. SNPs defining expression quantitative trait loci in Arabidopsis promoters are also enriched for predicted TF binding sites. Importantly, our motif "library" (http://cisbp.ccbr.utoronto.ca) can be used to identify specific TFs whose binding may be altered by human disease risk alleles. These data present a powerful resource for mapping transcriptional networks across eukaryotes.

Supplemental Text. Click to Download

Includes Extended Experimental Procedures, Supplemental Figure Titles and Legends, and small Supplemental Tables.

Supplemental Figures. Click to Download

Figure S1 (Related to Figure 1A). Pictorial overview of TF choosing strategy and motif inferences. This figure visually depicts the overall methodology in the form of a network.
Figure S2 (Related to Figure 2). Precisions obtained when combining together all DBD classes with insufficient available data to choose a cutoff. This figure shows boxplots that are identical to those shown in Figure 2, except these ones include data for the 32 DBD classes lacking sufficient data to establish thresholds.
Figure S3 (Related to Figure 6). Motifs enriched at specific positions in promoter regions, by species and DBD class. This figure is a heatmap depicting the number of motifs within each DBD class that are enriched in the promoter regions of various eukaryotes.
Figure S4 (Related to Figure 6). Results of motif TSS location enrichment, using sets of non-redundant motifs. This figure is identical to Figure 6, but here a reduced set of non-redundant motifs was used (as opposed to the full set of all motifs for all TFs in an organism).
Figure S5 (Related to Figure 7A). Arabidopsis eQTL analysis, using only inferred motifs. This figure is identical to Figure 7A, except in this case only TFs with motifs inferred from species other than Arabidopsis thaliana were included.
Figure S6 (Related to Figure 2). DBD class thresholds obtained for different measures of 8-mer similarity and different replicate percentiles. For each DBD class, DBD AA %ID inference threshold (based on precisions across DBD AA %ID bins) is plotted for each of the eight measures of 8-mer similarity.
Figure S7 (Related to Figure 5A). ChIP-seq comparison results obtained using an alternative null model. We repeated the procedure used to produce Figure 5A using an alternative set of background sequences - instead of scrambled peak sequences, we used real ChIP-seq peak sequences from an unrelated TF with the closest matching overall GC content in its peaks.

Supplemental Tables. Click to Download

Table S1 (Related to Figure 1B). Sources of other TF motifs. This table provides the sources we used to compile TF DNA binding motifs.
Table S2 (Related to Figure 1B). Full results of motif comparisons to other studies. This spreadsheet contains the TomTom P-values resulting from motif comparisons between those obtained in this study and previously determined motifs.
Table S3, part 1 (Related to Figure 4). Motif coverage by species and DBD class. This spreadsheet provides full information on the motif coverages (i.e., fraction direct, fraction inferred, etc.) for each species and DBD class.
Table S4 (Related to Figure 5). Full ChIP-seq AUROC results. This spreadsheet provides the AUROCs and %AA Identities for all motif/ChIP-seq study pairs.
Table S5 (Related to Figure 6). Motif GC content vs mean enrichment Z-score. This table provides the r2 value (across all of the motifs of an organism) between the motif's total GC content (i.e., the average across all of its positions) and its mean enrichment across all promoter positions relative to the TSS.
Table S6, DBD clone source material. This spreadsheet provides information on the clone source material, the experimental construct sequences, and the clone source contributors.

Files available in "Additional Data 1". Click to Download

AT-hook E-score Scatterplots (zipped .png image). This file depicts pairwise scatterplots of all 32,896 E-scores, for all pairs of TF plasmids assaying AT-hook TFs. The Pearson correlation, and its rank within all AT-hook pairs is indicated below each plot.
Boxplots for all DBD classes (zipped directory of .png images). These files provide boxplots similar to those depicted in Figure 2, for all DBD classes and all eight measures of 8-mer similarity.
DBD amino acid alignments for all DBD classes (gzipped tarball of directories). These files provide the DBD amino acid alignments for all DBD classes included in this study. See README.txt in root directory for more information.
Full results from leave-one-out cross validation analysis (.xlsx). This file contains the results of cross validation analysis of motif inferences.
Full results from human disease-associated genetic variants analysis (.xlsx). This file contains all human TFs predicted to differentially bind each disease-associated SNP.

Web supplement to
"Determination and Inference of Eukaryotic Transcription Factor Sequence Specificity"

Abstract

Supplemental Text. Click to Download

Supplemental Figures. Click to Download

Supplemental Tables. Click to Download

Files available in "Additional Data 1". Click to Download

Web Supplemental Files. Click to Download

PBM data are available in the CisBP database

Web supplement to "Determination and Inference of Eukaryotic Transcription Factor Sequence Specificity"

Abstract

Supplemental Text. Click to Download

Supplemental Figures. Click to Download

Supplemental Tables. Click to Download

Files available in "Additional Data 1". Click to Download

Web Supplemental Files. Click to Download

PBM data are available in the CisBP database

Web supplement to
"Determination and Inference of Eukaryotic Transcription Factor Sequence Specificity"