Comb-p: software for combining, analyzing, grouping and correcting spatially correlated P -values
Open accessAbstract
Summary: comb-p is a command-line tool and a python library that manipulates BED files of possibly irregularly spaced P-values and (1) calculates auto-correlation, (2) combines adjacent P-values, (3) performs false discovery adjustment, (4) finds regions of enrichment (i.e. series of adjacent low P-values) and (5) assigns significance to those regions. In addition, tools are provided for visualization and assessment. We provide validation and example uses on bisulfite-seq with P-values from Fisher’s exact test, tiled methylation probes using a linear model and Dam-ID for chromatin binding using moderated t-statistics. Because the library accepts input in a simple, standardized format and is unaffected by the origin of the P-values, it can be used for a wide variety of applications. Availability: comb-p is maintained under the BSD license. The documentation and implementation are available at https://github.com/brentp/combined-pvalues. Contact: bpederse@gmail.com
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?
comb-p software identified 24 DMRs in males at 5% Sidak multiple comparisons corrected P-value.
“the comb-p software [48] identified 41 differentially methylated regions (DMRs) in females and 24 different DMRs in males at 5% Sidak multiple comparisons corrected P-value”
From Distinct sex-specific DNA methylation differences in Alzheimer’s disease (2022) · cites this paper as [48]
comb-p software identified 41 differentially methylated regions (DMRs) in females at 5% Sidak multiple comparisons corrected P-value.
“the comb-p software [48] identified 41 differentially methylated regions (DMRs) in females and 24 different DMRs in males at 5% Sidak multiple comparisons corrected P-value”
From Distinct sex-specific DNA methylation differences in Alzheimer’s disease (2022) · cites this paper as [48]
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
No references could be resolved yet.
Research works printed but not linked: 13
- Biehs B, et al. Hedgehog targets in the Drosophila embryo and the mechanisms that generate tissue-specific outputs of Hedgehog signaling. Development. 2010;137:3887–3898. doi: 10.1242/dev.055871. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
- Fisher RA. Questions and answers #14. Am. Stat. 1948;2:30–31. [Google Scholar]
- Hsieh TF, et al. Genome-wide demethylation of Arabidopsis endosperm. Science. 2009;324:1451–1454. doi: 10.1126/science.1172417. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
- Irizarry RA, et al. Comprehensive high-throughput arrays for relative methylation (CHARM) Genome Res. 2008;18:780–790. doi: 10.1101/gr.7301508. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
- Irizarry RA, et al. The human colon cancer methylome shows similar hypo- and hypermethylation at conserved tissue-specific CpG island shores. Nat. Genet. 2009;41:178–186. doi: 10.1038/ng.298. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI · Paper page
- Kechris KJ, et al. Generalizing moving averages for tiling arrays using combined p-value statistic. Stat. Appl. Genet. Mol. Biol. 2010;9 doi: 10.2202/1544-6115.1434. Article 29. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
- Kent WJ, et al. The human genome browser at UCSC. Genome Res. 2002;12:996–1106. doi: 10.1101/gr.229102. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI · Paper page
- Liptak T. On the combination of independent tests. Magyar Tudomanyos. Akademia Matematikai Kutato Intezetenek Kozlemenyei. 1958;3:171–197. [Google Scholar]
- Pedersen BS, et al. MethylCoder: software pipeline for bisulfite-treated sequences. Bioinformatics. 2011;27:2435–2436. doi: 10.1093/bioinformatics/btr394. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
- Šidák Z. Rectangular confidence region for the means of multivariate normal distributions. J. Am. Stat. Assoc. 1967;62:626–633. [Google Scholar]
- Stouffer SA, et al. The American Soldier. Vol. 1: Adjustment during Army Life. Princeton, NJ: Princeton University Press; 1949. [Google Scholar]
- van Steensel B, et al. Chromatin profiling using targeted DNA adenine methyltransferase. Nat. Genet. 2001;27:304–308. doi: 10.1038/85871. [DOI] [PubMed] [Google Scholar] · DOI
- Zaykin DL, et al. Truncated product method for combining p-values. Genet. Epidemiol. 2002;22:170–185. doi: 10.1002/gepi.0042. [DOI] [PubMed] [Google Scholar] · DOI
Cited by
Sorted by citations
Methylomic profiling implicates cortical deregulation of ANK1 in Alzheimer's disease
Lunnon, K., Smith, R., Hannon, E., De Jager, P. L., Srivastava, G., Volta, M., Troakes, C., Al-Sarraj, S., Burrage, J., Macdonald, R., et al. (2014) · Nature Neuroscience · doi:10.1038/nn.3782 · Cited by 574 · see citing works
Hannon, E., Dempster, E., Viana, J., Burrage, J., Smith, A. R., Macdonald, R., St Clair, D., Mustard, C., Breen, G., Therman, S., et al. (2016) · Genome Biology · doi:10.1186/s13059-016-1041-x · Cited by 349 · see citing works
Histone deacetylase 6–mediated selective autophagy regulates COPD-associated cilia dysfunction
Lam, H. C., Cloonan, S. M., Bhashyam, A. R., Haspel, J. A., Singh, A., Sathirapongsasuti, J. F., Cervo, M., Yao, H., Chung, A. L., Mizumura, K., et al. (2013) · Journal of Clinical Investigation · doi:10.1172/jci69636 · Cited by 307 · see citing works
Making sense of the ageing methylome
Seale, K., Horvath, S., Teschendorff, A., Eynon, N., & Voisin, S. (2022) · Nature Reviews Genetics · doi:10.1038/s41576-022-00477-6 · Cited by 274 · see citing works
Smith, R. G., Hannon, E., De Jager, P. L., Chibnik, L., Lott, S. J., Condliffe, D., Smith, A. R., Haroutunian, V., Troakes, C., Al‐Sarraj, S., et al. (2018) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2018.01.017 · Cited by 184 · see citing works
Viana, J., Hannon, E., Dempster, E., Pidsley, R., Macdonald, R., Knox, O., Spiers, H., Troakes, C., Al-Saraj, S., Turecki, G., et al. (2016) · Human Molecular Genetics · doi:10.1093/hmg/ddw373 · Cited by 105 · see citing works
Cecil, C. A. M., Walton, E., Smith, R. G., Viding, E., McCrory, E. J., Relton, C. L., Suderman, M., Pingault, J.-B., McArdle, W., Gaunt, T. R., et al. (2016) · Translational Psychiatry · doi:10.1038/tp.2016.247 · Cited by 101 · see citing works
Wong, C. C. Y., Smith, R. G., Hannon, E., Ramaswami, G., Parikshak, N. N., Assary, E., Troakes, C., Poschmann, J., Schalkwyk, L. C., Sun, W., et al. (2019) · Human Molecular Genetics · doi:10.1093/hmg/ddz052 · Cited by 98 · see citing works
Mooney, M. A., Ryabinin, P., Wilmot, B., Bhatt, P., Mill, J., & Nigg, J. T. (2020) · Translational Psychiatry · doi:10.1038/s41398-020-0710-4 · Cited by 91 · see citing works
Roubroeks, J. A. Y., Smith, A. R., Smith, R. G., Pishva, E., Ibrahim, Z., Sattlecker, M., Hannon, E. J., Kłoszewska, I., Mecocci, P., Soininen, H., et al. (2020) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2020.06.023 · Cited by 82 · see citing works
5-hydroxymethylcytosine is highly dynamic across human fetal brain development
Spiers, H., Hannon, E., Schalkwyk, L. C., Bray, N. J., & Mill, J. (2017) · BMC Genomics · doi:10.1186/s12864-017-4091-x · Cited by 80 · see citing works
DNA methylation signatures in panic disorder
Iurato, S., Carrillo-Roa, T., Arloth, J., Czamara, D., Diener-Hölzl, L., Lange, J., Müller-Myhsok, B., Binder, E. B., & Erhardt, A. (2017) · Translational Psychiatry · doi:10.1038/s41398-017-0026-1 · Cited by 70 · see citing works
Genome-wide DNA methylation meta-analysis in the brains of suicide completers
Policicchio, S., Washer, S., Viana, J., Iatrou, A., Burrage, J., Hannon, E., Turecki, G., Kaminsky, Z., Mill, J., Dempster, E. L., et al. (2020) · Translational Psychiatry · doi:10.1038/s41398-020-0752-7 · Cited by 61 · see citing works
Epigenome-wide association study of alcohol use disorder in five brain regions
Zillich, L., Frank, J., Streit, F., Friske, M. M., Foo, J. C., Sirignano, L., Heilmann-Heimbach, S., Dukal, H., Degenhardt, F., Hoffmann, P., et al. (2022) · Neuropsychopharmacology · doi:10.1038/s41386-021-01228-7 · Cited by 36 · see citing works
Witt, S. H., Frank, J., Frischknecht, U., Treutlein, J., Streit, F., Foo, J. C., Sirignano, L., Dukal, H., Degenhardt, F., Koopmann, A., et al. (2020) · Addiction · doi:10.1111/add.15020 · Cited by 35 · see citing works
Distinct sex-specific DNA methylation differences in Alzheimer’s disease
C. Silva, T., Zhang, W., Young, J. I., Gomez, L., Schmidt, M. A., Varma, A., Chen, X. S., Martin, E. R., & Wang, L. (2022) · Alzheimer's Research & Therapy · doi:10.1186/s13195-022-01070-z · Cited by 33 · see citing works
“Differentially methylated regions analysis For region-based meta-analysis, we used the comb-p method [48].”
MethodMethylome-wide change associated with response to electroconvulsive therapy in depressed patients
Sirignano, L., Frank, J., Kranaster, L., Witt, S. H., Streit, F., Zillich, L., Sartorius, A., Rietschel, M., & Foo, J. C. (2021) · Translational Psychiatry · doi:10.1038/s41398-021-01474-9 · Cited by 32 · see citing works
Engelmann, J., Zillich, L., Frank, J., Wagner, S., Cetin, M., Herzog, D. P., Müller, M. B., Tadic, A., Foo, J. C., Sirignano, L., et al. (2022) · Translational Psychiatry · doi:10.1038/s41398-022-02032-7 · Cited by 29 · see citing works
- Authors
- Pedersen, B. S., Schwartz, D. A., Yang, I. V., & Kechris, K. J.
- Affiliations
- University of Colorado Anschutz (US)
- Corresponding author
- Pedersen, Brent S.
- Venue
- Bioinformatics
- Publisher
- Oxford University Press (OUP)
- Published
- 2012-09-05
- Volume
- 28
- Issue
- 22
- Pages
- 2986-2988
- ISSN
- 1367-4803 (ISSN-L)
- 1367-4811
- PMC
- PMC3496335
- OpenAlex
- W2129958809
- Cited by
- 485
- References
- 0
- Citations by year
- 2026: 32 · 2025: 50 · 2024: 63 · 2023: 64 · 2022: 59 · 2021: 46 · 2020: 41 · 2019: 40 · 2018: 29 · 2017: 21 · 2016: 16 · 2015: 10 · 2014: 10 · 2013: 4
- FWCI
- 3.09
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Bioinformatics (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01hl101251-05)
- National Institute on Alcohol Abuse and Alcoholism (K01AA016922, AA016922)
- National Heart, Lung, and Blood Institute (HL101715, RC2HL101715, HL101251)
- National Institute of Allergy and Infectious Diseases (AI90052)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioinformatics and Genomic Networks
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
- Keywords
- p-value combination, autocorrelation, BED files, bisulfite sequencing, DNA methylation, chromatin binding, Fisher's exact test, command-line tool, Python library
- MeSH terms
- Humans, Programming Languages, Software, DNA Probes, Sequence Analysis, DNA, Genomics, Genome-Wide Association Study
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
