PASTAA: identifying transcription factors associated with sets of co-regulated genes
Open accessAbstract
Motivation: A major challenge in regulatory genomics is the identification of associations between functional categories of genes (e.g. tissues, metabolic pathways) and their regulating transcription factors (TFs). While, for a limited number of categories, the regulating TFs are already known, still for many functional categories the responsible factors remain to be elucidated. Results: We put forward a novel method (PASTAA) for detecting transcriptions factors associated with functional categories, which utilizes the prediction of binding affinities of a TF to promoters. This binding strength information is compared to the likelihood of membership of the corresponding genes in the functional category under study. Coherence between the two ranked datasets is seen as an indicator of association between a TF and the category. PASTAA is applied primarily to the determination of TFs driving tissue-specific expression. We show that PASTAA is capable of recovering many TFs acting tissue specifically and, in addition, provides novel associations so far not detected by alternative methods. The application of PASTAA to detect TFs involved in the regulation of tissue-specific gene expression revealed a remarkable number of experimentally supported associations. The validated success for various datasets implies that PASTAA can directly be applied for the detection of TFs associated with newly derived gene sets. Availability: The PASTAA source code as well as a corresponding web interface is freely available at http://trap.molgen.mpg.de Contact: roider@molgen.mpg.de Supplementary information: Supplementary data are available at Bioinformatics online.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Pscan and PASTAA identified transcription factors that may coordinate the changes in protein levels in apoE4-expressing cells.
“To determine which regulatory pathways help compensate for apoE4-induced mitochondrial dysfunction, we used Pscan [64] and PASTAA [63] to identify transcription factors that may coordinate the changes in protein levels in apoE4-expressing cells (Table 1).”
From Neuronal Apolipoprotein E4 Expression Results in Proteome-Wide Alterations and Compromises Bioenergetic Capacity by Disrupting Mitochondrial Function (2019) · cites this paper as [63]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Genome-wide analysis of mammalian promoter architecture and evolution
Carninci, P., Sandelin, A., Lenhard, B., Katayama, S., Shimokawa, K., Ponjavic, J., Semple, C. A. M., Taylor, M. S., Engström, P. G., Frith, M. C., et al. (2006) · Nature Genetics · doi:10.1038/ng1789 · Cited by 1,350 · see citing works
Discovering motifs in ranked lists of DNA sequences
Eden, E., Lipson, D., Yogev, S., & Yakhini, Z. (2007) · PLoS Computational Biology · doi:10.1371/journal.pcbi.0030039 · Cited by 696 · see citing works
Flagged first, then by citations
Research works printed but not linked: 44
- Aoki KF Kanehisa M Unit 1. 12: Using the KEGG database resource, Chapter 1 Curr. Protoc. Bioinformatics. 2005 18428742
- Bailey TL Elkan C The value of prior knowledge in discovering motifs with MEME Proc. Int. Conf. Intell. Syst. Mol. Biol. 1995 3 21 29 7584439
- Birney E Ensembl 2006 Nucleic Acids Res. 2006 34 D556 D561 16381931 PMC1347495
- Chang LW PAP: a comprehensive workbench for mammalian transcriptional regulatory sequence analysis Nucleic Acids Res. 2007 35 W238 W244 17517777 PMC1933204
- Chen ZF NRSF/REST is required in vivo for repression of multiple neuronal target genes during embryogenesis Nat. Genet. 1998 20 136 142 9771705
- Dorval KM CHX10 targets a subset of photoreceptor genes J. Biol. Chem. 2006 281 744 751 16236706
- Engström PG Ancora: a web resource for exploring highly conserved noncoding elements and their association with developmental regulatory genes Genome Biol. 2008 9 R34.1 R34.12 18279518 PMC2374709
- Frith MC Detection of functional DNA motifs via statistical over-representation Nucleic Acids Res. 2004a 32 1372 1381 14988425 PMC390287
- Frith MC Finding functional sequence elements by multiple local alignment Nucleic Acids Res. 2004b 32 189 200 14704356 PMC373279
- Furukawa A The mouse Crx 5′-upstream transgene sequence directs cell-specific and developmentally regulated expression in retinal photoreceptor cells J. Neurosci. 2002 22 1640 1647 11880494 PMC6758905
- Grably MR HSF and Msn2/4p can exclusively or cooperatively activate the yeast HSP104 gene Mol. Microbiol. 2002 44 21 35 11967066
- Gupta S T-STAG: resource and web-interface for tissue-specific transcripts and genes Nucleic Acids Res. 2005 33 W654 W658 15980556 PMC1160111
- Haas SA GeneNest: automated generation and visualization of gene indices Trends Genet. 2000 16 521 523 12199289
- Harbison CT Transcriptional regulatory code of a eukaryotic genome Nature 2004 431 99 104 15343339 PMC3006441
- Hill DP Extension and integration of the Gene Ontology (GO): combining GO vocabularies with external vocabularies Genome Res. 2002 12 1982 1991 12466303 PMC187579
- Ho Sui SJ oPOSSUM: integrated tools for analysis of regulatory motif over-representation Nucleic Acids Res. 2007 35 W245 W252 17576675 PMC1933229
- Huber BR Bulyk ML Meta-analysis discovery of tissue-specific DNA sequence motifs from mammalian gene expression data BMC Bioinformatics 2006 7 229 16643658 PMC1522027
- Kaczynski J Sp1- and Kruppel-like transcription factors Genome Biol. 2003 4 206 12620113 PMC151296
- Kaestner KH Inactivation of the winged helix transcription factor HNF3alpha affects glucose homeostasis and islet glucagon gene expression in vivo Genes Dev. 1999 13 495 504 10049364 PMC316473
- Kimura S Thyroid-specific enhancer-binding protein/thyroid transcription factor 1 is not required for the initial specification of the thyroid and lung primordia Biochimie 1999 81 321 327 10401665
- Leone G Myc requires distinct E2F activities to induce S phase and apoptosis Mol. Cell 2001 8 105 113 11511364
- Li S Dwarf locus mutants lacking three pituitary cell types result from mutations in the POU-domain gene pit-1 Nature 1990 347 528 533 1977085
- Matys V TRANSFAC and its module TRANSCompel: transcriptional gene regulation in eukaryotes Nucleic Acids Res. 2006 34 D108 D110 16381825 PMC1347505
- Miyake T Genome-wide analysis of ARS (autonomously replicating sequence) binding factor 1 (Abf1p)-mediated transcriptional regulation in Saccharomyces cerevisiae J. Biol. Chem. 2004 279 34865 34872 15192094
- Mukherjee S Rapid analysis of the DNA-binding specificities of transcription factors with DNA microarrays Nat. Genet. 2004 36 1331 1339 15543148 PMC2692596
- Odom DT Control of pancreas and liver gene expression by HNF transcription factors Science 2004 303 1378 1381 14988562 PMC3012624
- Ohlsson H IPF1, a homeodomain-containing transactivator of the insulin gene Embo. J. 1993 12 4251 4259 7901001 PMC413720
- Pennacchio LA Predicting tissue-specific enhancers in the human genome Genome Res. 2007 17 201 211 17210927 PMC1781352
- Qian J Identification of regulatory targets of tissue-specific transcription factors: application to retina-specific gene regulation Nucleic Acids Res. 2005 33 3479 3491 15967807 PMC1153713
- Rahmann S On the power of profiles for transcription factor binding site detection Stat. Appl. Genet. Mol. Biol. 2003 2 Article 7 16646785
- Reith W RFX1, a transactivator of hepatitis B virus enhancer I, belongs to a novel family of homodimeric and heterodimeric DNA-binding proteins Mol. Cell Biol. 1994 14 1230 1244 8289803 PMC358479
- Roider HG Predicting transcription factor affinities to DNA from a biophysical model Bioinformatics 2007 23 134 141 17098775
- Roux E The cell-specific transcription factor PTF1 contains two different subunits that interact with the DNA Genes Dev. 1989 3 1613 1624 2612907
- Salmeron JM Jr Interaction between transcriptional activator protein LAC9 and negative regulatory protein GAL80 Mol. Cell Biol. 1989 9 2950 2956 2550790 PMC362763
- Sandelin A JASPAR: an open-access database for eukaryotic transcription factor binding profiles Nucleic Acids Res. 2004 32 D91 D94 14681366 PMC308747
- Sinha S Systematic functional characterization of cis-regulatory motifs in human core promoters Genome Res. 2008 18 477 488 18256240 PMC2259112
- Smith AD Mining ChIP-chip data for transcription factor and cofactor binding sites Bioinformatics 2005 21 Suppl. 1 i403 i412 15961485
- Smith AD DNA motifs in human and mouse proximal promoters predict tissue-specific expression Proc. Natl Acad. Sci. USA 2006 103 6275 6280 16606849 PMC1458868
- Springer M Partially phosphorylated Pho4 activates transcription of a subset of phosphate responsive genes PLoS Biol. 2003 1 E28 14624238 PMC261874
- van Helden J Discovering regulatory elements in non-coding sequences by analysis of spaced dyads Nucleic Acids Res. 2000 28 1808 1818 10734201 PMC102821
- Warner JB Systematic identification of mammalian regulatory motifs' target genes and functions Nat. Methods 2008 5 347 353 18311145 PMC2708972
- Wasserman WW Fickett JW Identification of regulatory regions which confer muscle-specific gene expression J. Mol. Biol. 1998 278 167 181 9571041
- Yu X Computational analysis of tissue-specific combinatorial gene regulation: predicting interaction between transcription factors in human tissues Nucleic Acids Res. 2006 34 4925 4936 16982645 PMC1635265
- Zeller KI Global mapping of c-myc binding sites and target gene networks in human B cells Proc. Natl Acad. Sci. USA 2006 103 17834 17839 17093053 PMC1635161
Cited by
Sorted by citations
The transcription factor Myc controls metabolic reprogramming upon T lymphocyte activation
Wang, R., Dillon, C. P., Shi, L. Z., Milasta, S., Carter, R., Finkelstein, D., McCormick, L. L., Fitzgerald, P., Chi, H., Munger, J., et al. (2011) · Immunity · doi:10.1016/j.immuni.2011.09.021 · Cited by 2,140 · see citing works
“I Myc, but Not HIF1a, Is Required for Activation-Induced T Cell Metabolic Reprogramming With an in silico approach (Roider et al., 2009), transcription factors possibly involved in activation-induced T cell metabolic mmunity 35, 871–882, December 23, 2011 ª2011 Elsevier Inc. 873 (A andB) The…”
BackgroundMethodInfluentialiRegulon: From a Gene List to a Gene Regulatory Network Using Large Motif and Track Collections
Janky, R., Verfaillie, A., Imrichová, H., Van de Sande, B., Standaert, L., Christiaens, V., Hulselmans, G., Herten, K., Naval Sanchez, M., Potier, D., et al. (2014) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1003731 · Cited by 900 · see citing works
“As motif discovery method we have chosen to elaborate on the recent ranking-and-recovery methods [28–32] (Fig.”
MethodSingle cell RNA sequencing of human microglia uncovers a subset associated with Alzheimer’s disease
Olah, M., Menon, V., Habib, N., Taga, M. F., Ma, Y., Yung, C. J., Cimpean, M., Khairallah, A., Coronas-Samano, G., Sankowski, R., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-19737-2 · Cited by 722 · see citing works
Genetic adaptation and Neandertal admixture shaped the immune system of human populations
Quach, H., Rotival, M., Pothlichet, J., Loh, Y.-H. E., Dannemann, M., Zidane, N., Laval, G., Patin, E., Harmant, C., Lopez, M., et al. (2016) · Cell · doi:10.1016/j.cell.2016.09.024 · Cited by 475 · see citing works
A trans-acting locus regulates an anti-viral expression network and type 1 diabetes risk
Cardiogenics Consortium, Heinig, M., Petretto, E., Wallace, C., Bottolo, L., Rotival, M., Lu, H., Li, Y., Sarwar, R., Langley, S. R., et al. (2010) · Nature · doi:10.1038/nature09386 · Cited by 283 · see citing works
Self-citationKrishnan, M. L., Van Steenwinckel, J., Schang, A.-L., Yan, J., Arnadottir, J., Le Charpentier, T., Csaba, Z., Dournaud, P., Cipriani, S., Auvynet, C., et al. (2017) · Nature Communications · doi:10.1038/s41467-017-00422-w · Cited by 105 · see citing works
Orr, A. L., Kim, C., Jimenez-Morales, D., Newton, B. W., Johnson, J. R., Krogan, N. J., Swaney, D. L., & Mahley, R. W. (2019) · Journal of Alzheimer's Disease · doi:10.3233/jad-181184 · Cited by 103 · see citing works
Genetic influences on brain gene expression in rats selected for tameness and aggression
Heyne, H. O., Lautenschläger, S., Nelson, R., Besnier, F., Rotival, M., Cagan, A., Kozhemyakina, R., Plyusnina, I. Z., Trut, L., Carlborg, Ö., et al. (2014) · Genetics · doi:10.1534/genetics.114.168948 · Cited by 72 · see citing works
Xiao, X., Moreno-Moral, A., Rotival, M., Bottolo, L., & Petretto, E. (2014) · PLoS Genetics · doi:10.1371/journal.pgen.1004006 · Cited by 63 · see citing works
- Authors
- Roider, H. G., Manke, T., O'Keeffe, S., Vingron, M., & Haas, S. A.
- Affiliations
- Max Planck Society (DE)
- Max Planck Institute for Molecular Genetics, Ihnestrasse 73, 14195 Berlin
- Max Planck Institute for Molecular Genetics (DE)
- Corresponding author
- Roider, Helge G.
- Venue
- Bioinformatics
- Publisher
- Oxford University Press (OUP)
- Published
- 2008-12-09
- Volume
- 25
- Issue
- 4
- Pages
- 435-442
- ISSN
- 1367-4803 (ISSN-L)
- 1367-4811
- PMC
- PMC2642637
- OpenAlex
- W2133045519
- Cited by
- 154
- References
- 2
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 3 · 2023: 11 · 2022: 9 · 2021: 7 · 2020: 18 · 2019: 6 · 2018: 6 · 2017: 11 · 2016: 9 · 2015: 10 · 2014: 10 · 2013: 8 · 2012: 12
- FWCI
- 3.84
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Bioinformatics (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion, other-oa)
- Max Planck Institute for Plasma Physics (submittedVersion, other-oa)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioinformatics and Genomic Networks
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene Regulatory Network Analysis
- Keywords
- transcription factors, co-regulated genes, functional categories, tissue-specific gene expression, promoter binding, regulatory genomics
- MeSH terms
- Binding Sites, Gene Expression Regulation, Promoter Regions, Genetic, Software, Transcription Factors, Expressed Sequence Tags, Gene Expression Profiling, Databases, Genetic, Chromatin Immunoprecipitation
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review