MetArea: a software package for analysis of the mutually exclusive occurrence in pairs of motifs of transcription factor binding sites based on ChIP-seq data

ChIP-seq technology, which is based on chromatin immunoprecipitation (ChIP), allows mapping a set of genomic loci (peaks) containing binding sites (BS) for the investigated (target) transcription factor (TF). A TF may recognize several structurally different BS motifs. The multiprotein complex mappe...

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Main Authors: V. G. Levitsky, A. V. Tsukanov, T. I. Merkulova
Format: Article
Language:English
Published: Siberian Branch of the Russian Academy of Sciences, Federal Research Center Institute of Cytology and Genetics, The Vavilov Society of Geneticists and Breeders 2025-01-01
Series:Вавиловский журнал генетики и селекции
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Online Access:https://vavilov.elpub.ru/jour/article/view/4404
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author V. G. Levitsky
A. V. Tsukanov
T. I. Merkulova
author_facet V. G. Levitsky
A. V. Tsukanov
T. I. Merkulova
author_sort V. G. Levitsky
collection DOAJ
description ChIP-seq technology, which is based on chromatin immunoprecipitation (ChIP), allows mapping a set of genomic loci (peaks) containing binding sites (BS) for the investigated (target) transcription factor (TF). A TF may recognize several structurally different BS motifs. The multiprotein complex mapped in a ChIP-seq experiment includes target and other “partner” TFs linked by protein-protein interactions. Not all these TFs bind to DNA directly. Therefore, both target and partner TFs recognize enriched BS motifs in peaks. A de novo search approach is used to search for enriched TF BS motifs in ChIP-seq data. For a pair of enriched BS motifs of TFs, the co-occurrence or mutually exclusive occurrence can be detected from a set of peaks: the co-occurrence reflects a more frequent occurrence of two motifs in the same peaks, while the mutually exclusive means their more frequent detection in different peaks. We propose the MetArea software package to identify pairs of TF BS motifs with the mutually exclusive occurrence in ChIP-seq data. MetArea was designed to predict the structural diversity of BS motifs of the same TFs, and the functional relation of BS motifs of different TFs. The functional relation of the motifs of the two distinct TFs presumes that they are interchangeable as part of a multiprotein complex that uses the BS of these TFs to bind directly to DNA in different peaks. MetArea calculates the estimates of recognition performance pAUPRC (partial area under the Precision–Recall curve) for each of the two input single motifs, identifies the “joint” motif, and computes the performance for it too. The goal of the analysis is to find pairs of single motifs A and B for which the accuracy of the joint A&B motif is higher than those of both single motifs.
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institution Kabale University
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publishDate 2025-01-01
publisher Siberian Branch of the Russian Academy of Sciences, Federal Research Center Institute of Cytology and Genetics, The Vavilov Society of Geneticists and Breeders
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spelling doaj-art-2f9f6f1377fb405bb4d827e72d2bd6c62025-02-01T09:58:14ZengSiberian Branch of the Russian Academy of Sciences, Federal Research Center Institute of Cytology and Genetics, The Vavilov Society of Geneticists and BreedersВавиловский журнал генетики и селекции2500-32592025-01-0128882283310.18699/vjgb-24-901517MetArea: a software package for analysis of the mutually exclusive occurrence in pairs of motifs of transcription factor binding sites based on ChIP-seq dataV. G. Levitsky0A. V. Tsukanov1T. I. Merkulova2Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences; Novosibirsk State UniversityInstitute of Cytology and Genetics of the Siberian Branch of the Russian Academy of SciencesInstitute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences; Novosibirsk State UniversityChIP-seq technology, which is based on chromatin immunoprecipitation (ChIP), allows mapping a set of genomic loci (peaks) containing binding sites (BS) for the investigated (target) transcription factor (TF). A TF may recognize several structurally different BS motifs. The multiprotein complex mapped in a ChIP-seq experiment includes target and other “partner” TFs linked by protein-protein interactions. Not all these TFs bind to DNA directly. Therefore, both target and partner TFs recognize enriched BS motifs in peaks. A de novo search approach is used to search for enriched TF BS motifs in ChIP-seq data. For a pair of enriched BS motifs of TFs, the co-occurrence or mutually exclusive occurrence can be detected from a set of peaks: the co-occurrence reflects a more frequent occurrence of two motifs in the same peaks, while the mutually exclusive means their more frequent detection in different peaks. We propose the MetArea software package to identify pairs of TF BS motifs with the mutually exclusive occurrence in ChIP-seq data. MetArea was designed to predict the structural diversity of BS motifs of the same TFs, and the functional relation of BS motifs of different TFs. The functional relation of the motifs of the two distinct TFs presumes that they are interchangeable as part of a multiprotein complex that uses the BS of these TFs to bind directly to DNA in different peaks. MetArea calculates the estimates of recognition performance pAUPRC (partial area under the Precision–Recall curve) for each of the two input single motifs, identifies the “joint” motif, and computes the performance for it too. The goal of the analysis is to find pairs of single motifs A and B for which the accuracy of the joint A&amp;B motif is higher than those of both single motifs.https://vavilov.elpub.ru/jour/article/view/4404<i>de novo</i> motif searchpr curvearea under curvestructural variants of transcription factor binding site motifscooperative action of transcription factors
spellingShingle V. G. Levitsky
A. V. Tsukanov
T. I. Merkulova
MetArea: a software package for analysis of the mutually exclusive occurrence in pairs of motifs of transcription factor binding sites based on ChIP-seq data
Вавиловский журнал генетики и селекции
<i>de novo</i> motif search
pr curve
area under curve
structural variants of transcription factor binding site motifs
cooperative action of transcription factors
title MetArea: a software package for analysis of the mutually exclusive occurrence in pairs of motifs of transcription factor binding sites based on ChIP-seq data
title_full MetArea: a software package for analysis of the mutually exclusive occurrence in pairs of motifs of transcription factor binding sites based on ChIP-seq data
title_fullStr MetArea: a software package for analysis of the mutually exclusive occurrence in pairs of motifs of transcription factor binding sites based on ChIP-seq data
title_full_unstemmed MetArea: a software package for analysis of the mutually exclusive occurrence in pairs of motifs of transcription factor binding sites based on ChIP-seq data
title_short MetArea: a software package for analysis of the mutually exclusive occurrence in pairs of motifs of transcription factor binding sites based on ChIP-seq data
title_sort metarea a software package for analysis of the mutually exclusive occurrence in pairs of motifs of transcription factor binding sites based on chip seq data
topic <i>de novo</i> motif search
pr curve
area under curve
structural variants of transcription factor binding site motifs
cooperative action of transcription factors
url https://vavilov.elpub.ru/jour/article/view/4404
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AT avtsukanov metareaasoftwarepackageforanalysisofthemutuallyexclusiveoccurrenceinpairsofmotifsoftranscriptionfactorbindingsitesbasedonchipseqdata
AT timerkulova metareaasoftwarepackageforanalysisofthemutuallyexclusiveoccurrenceinpairsofmotifsoftranscriptionfactorbindingsitesbasedonchipseqdata