Cargando…
BiFET: sequencing Bias-free transcription factor Footprint Enrichment Test
Transcription factor (TF) footprinting uncovers putative protein–DNA binding via combined analyses of chromatin accessibility patterns and their underlying TF sequence motifs. TF footprints are frequently used to identify TFs that regulate activities of cell/condition-specific genomic regions (targe...
Autores principales: | , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6344870/ https://www.ncbi.nlm.nih.gov/pubmed/30428075 http://dx.doi.org/10.1093/nar/gky1117 |
_version_ | 1783389489740120064 |
---|---|
author | Youn, Ahrim Marquez, Eladio J Lawlor, Nathan Stitzel, Michael L Ucar, Duygu |
author_facet | Youn, Ahrim Marquez, Eladio J Lawlor, Nathan Stitzel, Michael L Ucar, Duygu |
author_sort | Youn, Ahrim |
collection | PubMed |
description | Transcription factor (TF) footprinting uncovers putative protein–DNA binding via combined analyses of chromatin accessibility patterns and their underlying TF sequence motifs. TF footprints are frequently used to identify TFs that regulate activities of cell/condition-specific genomic regions (target loci) in comparison to control regions (background loci) using standard enrichment tests. However, there is a strong association between the chromatin accessibility level and the GC content of a locus and the number and types of TF footprints that can be detected at this site. Traditional enrichment tests (e.g. hypergeometric) do not account for this bias and inflate false positive associations. Therefore, we developed a novel post-processing method, Bias-free Footprint Enrichment Test (BiFET), that corrects for the biases arising from the differences in chromatin accessibility levels and GC contents between target and background loci in footprint enrichment analyses. We applied BiFET on TF footprint calls obtained from EndoC-βH1 ATAC-seq samples using three different algorithms (CENTIPEDE, HINT-BC and PIQ) and showed BiFET’s ability to increase power and reduce false positive rate when compared to hypergeometric test. Furthermore, we used BiFET to study TF footprints from human PBMC and pancreatic islet ATAC-seq samples to show its utility to identify putative TFs associated with cell-type-specific loci. |
format | Online Article Text |
id | pubmed-6344870 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-63448702019-01-29 BiFET: sequencing Bias-free transcription factor Footprint Enrichment Test Youn, Ahrim Marquez, Eladio J Lawlor, Nathan Stitzel, Michael L Ucar, Duygu Nucleic Acids Res Methods Online Transcription factor (TF) footprinting uncovers putative protein–DNA binding via combined analyses of chromatin accessibility patterns and their underlying TF sequence motifs. TF footprints are frequently used to identify TFs that regulate activities of cell/condition-specific genomic regions (target loci) in comparison to control regions (background loci) using standard enrichment tests. However, there is a strong association between the chromatin accessibility level and the GC content of a locus and the number and types of TF footprints that can be detected at this site. Traditional enrichment tests (e.g. hypergeometric) do not account for this bias and inflate false positive associations. Therefore, we developed a novel post-processing method, Bias-free Footprint Enrichment Test (BiFET), that corrects for the biases arising from the differences in chromatin accessibility levels and GC contents between target and background loci in footprint enrichment analyses. We applied BiFET on TF footprint calls obtained from EndoC-βH1 ATAC-seq samples using three different algorithms (CENTIPEDE, HINT-BC and PIQ) and showed BiFET’s ability to increase power and reduce false positive rate when compared to hypergeometric test. Furthermore, we used BiFET to study TF footprints from human PBMC and pancreatic islet ATAC-seq samples to show its utility to identify putative TFs associated with cell-type-specific loci. Oxford University Press 2019-01-25 2018-11-14 /pmc/articles/PMC6344870/ /pubmed/30428075 http://dx.doi.org/10.1093/nar/gky1117 Text en © The Author(s) 2018. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Methods Online Youn, Ahrim Marquez, Eladio J Lawlor, Nathan Stitzel, Michael L Ucar, Duygu BiFET: sequencing Bias-free transcription factor Footprint Enrichment Test |
title | BiFET: sequencing Bias-free transcription factor Footprint Enrichment Test |
title_full | BiFET: sequencing Bias-free transcription factor Footprint Enrichment Test |
title_fullStr | BiFET: sequencing Bias-free transcription factor Footprint Enrichment Test |
title_full_unstemmed | BiFET: sequencing Bias-free transcription factor Footprint Enrichment Test |
title_short | BiFET: sequencing Bias-free transcription factor Footprint Enrichment Test |
title_sort | bifet: sequencing bias-free transcription factor footprint enrichment test |
topic | Methods Online |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6344870/ https://www.ncbi.nlm.nih.gov/pubmed/30428075 http://dx.doi.org/10.1093/nar/gky1117 |
work_keys_str_mv | AT younahrim bifetsequencingbiasfreetranscriptionfactorfootprintenrichmenttest AT marquezeladioj bifetsequencingbiasfreetranscriptionfactorfootprintenrichmenttest AT lawlornathan bifetsequencingbiasfreetranscriptionfactorfootprintenrichmenttest AT stitzelmichaell bifetsequencingbiasfreetranscriptionfactorfootprintenrichmenttest AT ucarduygu bifetsequencingbiasfreetranscriptionfactorfootprintenrichmenttest |