Benchmark and integration of resources for the estimation of human transcription factor activities
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Abstract
The prediction of transcription factor (TF) activities from the gene expression of their targets (i.e., TF regulon) is becoming a widely used approach to characterize the functional status of transcriptional regulatory circuits. Several strategies and data sets have been proposed to link the target genes likely regulated by a TF, each one providing a different level of evidence. The most established ones are (1) manually curated repositories, (2) interactions derived from ChIP-seq binding data, (3) in silico prediction of TF binding on gene promoters, and (4) reverse-engineered regulons from large gene expression data sets. However, it is not known how these different sources of regulons affect the TF activity estimations and, thereby, downstream analysis and interpretation. Here we compared the accuracy and biases of these strategies to define human TF regulons by means of their ability to predict changes in TF activities in three reference benchmark data sets. We assembled a collection of TF–target interactions for 1541 human TFs and evaluated how different molecular and regulatory properties of the TFs, such as the DNA-binding domain, specificities, or mode of interaction with the chromatin, affect the predictions of TF activity. We assessed their coverage and found little overlap on the regulons derived from each strategy and better performance by literature-curated information followed by ChIP-seq data. We provide an integrated resource of all TF–target interactions derived through these strategies, with confidence scores, as a resource for enhanced prediction of TF activities.
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Our sample sizes for experiments were chosen based on our prior publication using APP/PS1 mice, which defined the expectations for the effect size and variance.
“Our sample sizes for experiments were chosen based on our prior publication using APP/PS1 mice 58 , which defined the expectations for the effect size and variance 55 .”
From Identification of a protective microglial state mediated by miR-155 and interferon-γ signaling in a mouse model of Alzheimer’s disease (2023) · cites this paper as [55]
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Self-citationDefining Cardiac Recovery at Single Cell Resolution
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- Authors
- García‐Alonso, L., Holland, C. H., Ibrahim, M. M., Türei, D., & Sáez-Rodríguez, J.
- Affiliations
- European Bioinformatics Institute (GB)
- Heidelberg University (DE)
- RWTH Aachen University (DE)
- Venue
- Genome Research
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2019-07-24
- Volume
- 29
- Issue
- 8
- Pages
- 1363-1375
- ISSN
- 1088-9051 (ISSN-L)
- 1549-5469
- PMC
- PMC6673718
- OpenAlex
- W2964315448
- Cited by
- 1,122
- References
- 9
- Citations by year
- 2026: 221 · 2025: 192 · 2024: 240 · 2023: 180 · 2022: 146 · 2021: 88 · 2020: 43 · 2019: 11
- Type
- posted content
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- other-oa
- Locations
- Genome Research (publishedVersion, other-oa)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- RWTH Publications (RWTH Aachen) (submittedVersion, other-oa)
- Zenodo (CERN European Organization for Nuclear Research) (submittedVersion, cc-by)
- RWTH Publications (RWTH Aachen)
- Funders
- Open Targets (OTAR016)
- Germany Federal Ministry of Education and Research (FKZ 031L0041)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene Regulatory Network Analysis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioinformatics and Genomic Networks
- Keywords
- transcription factor regulons, human transcription factors, confidence scores
- MeSH terms
- Binding Sites, Chromatin, DNA, Neoplasm, Humans, Neoplasm Proteins, Neoplasms, Promoter Regions, Genetic, Protein Binding, Transcription Factors, Transcription, Genetic, Regulon, Computational Biology, Benchmarking, Chromatin Immunoprecipitation, Gene Regulatory Networks, Datasets as Topic
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.
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