{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,4]],"date-time":"2026-04-04T13:19:39Z","timestamp":1775308779946,"version":"3.50.1"},"reference-count":20,"publisher":"Oxford University Press (OUP)","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2010,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Motivation:ChIP-seq is becoming the main approach to the genome-wide study of protein\u2013DNA 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.<\/jats:p><jats:p>Results: We propose a linear signal\u2013noise 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.<\/jats:p><jats:p>Availability: \u00a0http:\/\/cmb.gis.a-star.edu.sg\/ChIPSeq\/tools.htm<\/jats:p><jats:p>Contact: \u00a0sungk@gis.a-star.edu.sg; asflin@ntu.edu.sg<\/jats:p><jats:p>Supplementary Information: \u00a0Supplementary data are available at Bioinformatics online.<\/jats:p>","DOI":"10.1093\/bioinformatics\/btq128","type":"journal-article","created":{"date-parts":[[2010,4,7]],"date-time":"2010-04-07T05:37:32Z","timestamp":1270618652000},"page":"1199-1204","source":"Crossref","is-referenced-by-count":120,"title":["A signal\u2013noise model for significance analysis of ChIP-seq with negative control"],"prefix":"10.1093","volume":"26","author":[{"given":"Han","family":"Xu","sequence":"first","affiliation":[{"name":"1 Computational & Mathematical Biology Group, Genome Institute of Singapore, 138672, 2 School of Computer Engineering, Nanyang 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