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The work addresses two gaps: the detectability of weak ChIP signals and whether such weak sites carry biological meaning. It introduces a linear signal–noise model using a noise rate estimated from a control library and applies a library-swapping strategy for false discovery rate control, yielding CCAT.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/a-signalnoise-model-for-significance-analysis-of-chip-seq-with-negative-control-ccat-control-based-chip-seq-analysis-tool/501867/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/a-signalnoise-model-for-significance-analysis-of-chip-seq-with-negative-control-ccat-control-based-chip-seq-analysis-tool/501867.png","ImageObject",300,407,{"name":92,"@type":93},"cksankcs","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-18","2026-10-03",true,{"@type":102,"interactionType":103,"userInteractionCount":81},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What problem does the signal–noise model address in ChIP-seq analysis?","Question",{"text":112,"@type":113},"It separates weak ChIP enrichment from background noise so that weak ChIP-enriched sites can be identified and assessed for biological meaning.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How is the noise rate estimated in the proposed method?",{"text":117,"@type":113},"A noise rate is introduced in a linear signal–noise model and is estimated iteratively using a control library.",{"name":119,"@type":110,"acceptedAnswer":120},"What is the purpose of the library-swapping strategy in CCAT?",{"text":121,"@type":113},"It supports false discovery rate estimation to improve significance analysis beyond P-value correction.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},501867,1792006351,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":81,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":29,"language":139,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":67,"update_tm":143,"read_time":144},3985747882755,"https://ap-avatar.wpscdn.com/davatar_29158cc5080c5b710cf443261637dec0","BIOINFORMATICS  \nORIGINAL PAPER  \nVol. 26 no. 9 2010, pages 1199–1204 doi:10. 1093/bioinformatics/btq128  \n\n| Gene expression Advance Access publication April 5, 2010\u003Cbr>A signal–noise model for significance analysis of ChIP-seq with negative control\u003Cbr>Han Xu 1 ,2 , Lusy Handoko3 , Xueliang Wei4 , Chaopeng Ye3 , Jianpeng Sheng5 , Chia-Lin Wei3 , Feng Lin2 ,∗ and Wing-Kin Sung 1 ,4 , ∗\u003Cbr>1 Computational & Mathematical Biology Group, Genome Institute of Singapore, 138672, 2 School of\u003Cbr>Computer Engineering, Nanyang Technological University, 637553, 3 Genome Technology & Biology Group, Genome Institute of Singapore, 138672, 4 School of Computing, National University of Singapore, 117543 and 5 School of Biological Science, Nanyang Technological University, 637551, Singapore\u003Cbr>Associate Editor: Joaquin Dopazo |  |\n| --- | --- |\n| ABSTRACT\u003Cbr>Motivation: ChIP-seq is becoming the main approach to the genome-wide study of protein–DNA interactions and histone modifications. Existing informatics tools perform well to extract strong ChIP-enriched sites. However, two questions remain to be answered: (i) to which extent is a ChIP-seq experiment able to reveal the weak ChIP-enriched sites? (ii) are the weak sites biologically meaningful? To answer these questions, it is necessary to identify the weak ChIP signals from background noise.\u003Cbr>Results: We propose a linear signal–noise model, in which a noise rate was introduced to represent the fraction of noise in a ChIP library. We developed an iterative algorithm to estimate the noise rate using a control library, and derived a library-swapping strategy for the false discovery rate estimation. These approaches were integrated in a general-purpose framework, named CCAT (Control-based ChIP-seq Analysis Tool), for the significance analysis of ChIP-seq. Applications to H3K4me3 and H3K36me3 datasets showed that CCAT predicted significantly more ChIP-enriched sites that the previous methods did. With the high sensitivity of CCAT prediction, we revealed distinct chromatin features associated to the strong and weak H3K4me3 sites.\u003Cbr>Availability: [http://cmb.gis.a-star.edu.sg/ChIPSeq/tools.htm](http://cmb.gis.a-star.edu.sg/ChIPSeq/tools.htm)\u003Cbr>Contact: [sungk@gis.a-star.edu.sg](sungk@gis.a-star.edu.sg); asfl[in@ntu.edu.sg](in@ntu.edu.sg)\u003Cbr>Supplementary Information: Supplementary data are available at Bioinformatics online.\u003Cbr>Received on October 7, 2009; revised on March 17, 2010; accepted on March 18, 2010\u003Cbr>1 INTRODUCTION\u003Cbr>With the advances of ultra-high-throughput sequencing technologies in the past 3 years, ChIP-seq is becoming the main approach to the genome-wide study of protein–DNA interactions and histone modifications (Barski et al., 2007; Johnson et al., 2007). In ChIP-seq analysis, the biologically interesting sites are identified by searching for the genomic loci where the reads sequenced from ChIP DNA are over-represented. A number of ChIP-seq analysis tools have been developed for this purpose (Ji et al., 2008; Jothi et al., 2008; Robertson et al., 2007; Rozowsky et al., 2009; Valouev et al., 2008;\u003Cbr>∗ To whom correspondence should be addressed. | Zang et al., 2009; Zhang et al., 2008) . All these tools perform well to extract strong ChIP-enriched sites. However, two questions remain to be answered: (i) to which extent is a ChIP-seq experiment able to reveal the weak ChIP-enriched sites? (ii) are the weak sites biologically meaningful? To answer these questions, it is necessary to establish a signal–noise model to separate the weak ChIP signals from background noise.\u003Cbr>In a ChIP-seq experiment, majority of the unbound DNA fragments are washed out in the immune-precipitation procedure. The ChIP-processed library is enriched by the fragments pulled down from the genomic loci with high chance of protein–DNA interactions or histone modifications. However, considerable ‘nonuseful’ fragments remain in the library due to the random protein– DNA or antibody–DNA contacts that are not positio","cbCailajKefuH30R","https://ap.wps.com/l/cbCailajKefuH30R","pdf",358713,"English","# Abstract\n## Motivation\n## Results\n## Introduction\n### Background noise and limitations of uniform models\n### Negative controls and prior normalization approaches\n### CCAT framework and performance notes","[{\"question\":\"What problem does the signal–noise model address in ChIP-seq analysis?\",\"answer\":\"It separates weak ChIP enrichment from background noise so that weak ChIP-enriched sites can be identified and assessed for biological meaning.\"},{\"question\":\"How is the noise rate estimated in the proposed method?\",\"answer\":\"A noise rate is introduced in a linear signal–noise model and is estimated iteratively using a control library.\"},{\"question\":\"What is the purpose of the library-swapping strategy in CCAT?\",\"answer\":\"It supports false discovery rate estimation to improve significance analysis beyond P-value correction.\"}]","A signal–noise model for significance analysis of ChIP-seq with negative control - CCAT (Control-based ChIP-seq Analysis Tool) | PDF",1791026087,15]