TY - JOUR

T1 - Novel ChIP-seq simulating program with superior versatility: isChIP

AU - Subkhankulova, Tatiana

AU - Naumenko, Fedor

AU - Tolmachov, Oleg E.

AU - Orlov, Yuriy L.

N1 - Publisher Copyright: © The Author(s) 2020. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

PY - 2021/7/1

Y1 - 2021/7/1

N2 - Chromatin immunoprecipitation followed by next-generation sequencing (ChIP-seq) is recognized as an extremely powerful tool to study the interaction of numerous transcription factors and other chromatin-associated proteins with DNA. The core problem in the optimization of ChIP-seq protocol and the following computational data analysis is that a 'true' pattern of binding events for a given protein factor is unknown. Computer simulation of the ChIP-seq process based on 'a-priory known binding template' can contribute to a drastically reduce the number of wet lab experiments and finally help achieve radical optimization of the entire processing pipeline. We present a newly developed ChIP-sequencing simulation algorithm implemented in the novel software, in silico ChIP-seq (isChIP). We demonstrate that isChIP closely approximates real ChIP-seq protocols and is able to model data similar to those obtained from experimental sequencing. We validated isChIP using publicly available datasets generated for well-characterized transcription factors Oct4 and Sox2. Although the novel software is compatible with the Illumina protocols by default, it can also successfully perform simulations with a number of alternative sequencing platforms such as Roche454, Ion Torrent and SOLiD as well as model ChIP -Exo. The versatility of isChIP was demonstrated through modelling a wide range of binding events, including those of transcription factors and chromatin modifiers. We also performed a comparative analysis against a few existing ChIP-seq simulators and showed the fundamental superiority of our model. Due to its ability to utilize known binding templates, isChIP can potentially be employed to help investigators choose the most appropriate analytical software through benchmarking of available ChIP-seq programs and optimize the experimental parameters of ChIP-seq protocol. isChIP software is freely available at https://github.com/fnaumenko/isChIP.

AB - Chromatin immunoprecipitation followed by next-generation sequencing (ChIP-seq) is recognized as an extremely powerful tool to study the interaction of numerous transcription factors and other chromatin-associated proteins with DNA. The core problem in the optimization of ChIP-seq protocol and the following computational data analysis is that a 'true' pattern of binding events for a given protein factor is unknown. Computer simulation of the ChIP-seq process based on 'a-priory known binding template' can contribute to a drastically reduce the number of wet lab experiments and finally help achieve radical optimization of the entire processing pipeline. We present a newly developed ChIP-sequencing simulation algorithm implemented in the novel software, in silico ChIP-seq (isChIP). We demonstrate that isChIP closely approximates real ChIP-seq protocols and is able to model data similar to those obtained from experimental sequencing. We validated isChIP using publicly available datasets generated for well-characterized transcription factors Oct4 and Sox2. Although the novel software is compatible with the Illumina protocols by default, it can also successfully perform simulations with a number of alternative sequencing platforms such as Roche454, Ion Torrent and SOLiD as well as model ChIP -Exo. The versatility of isChIP was demonstrated through modelling a wide range of binding events, including those of transcription factors and chromatin modifiers. We also performed a comparative analysis against a few existing ChIP-seq simulators and showed the fundamental superiority of our model. Due to its ability to utilize known binding templates, isChIP can potentially be employed to help investigators choose the most appropriate analytical software through benchmarking of available ChIP-seq programs and optimize the experimental parameters of ChIP-seq protocol. isChIP software is freely available at https://github.com/fnaumenko/isChIP.

KW - binding site/domain

KW - binding template

KW - ChIP-seq

KW - ChIP-seq modelling/simulation

KW - fragment size distribution

KW - peak-calling programs

KW - single cell ChIP-seq simulation

KW - transcription factor

UR - http://www.scopus.com/inward/record.url?scp=85112130417&partnerID=8YFLogxK

U2 - 10.1093/bib/bbaa352

DO - 10.1093/bib/bbaa352

M3 - Review article

C2 - 33320934

AN - SCOPUS:85112130417

VL - 22

JO - Briefings in Bioinformatics

JF - Briefings in Bioinformatics

SN - 1467-5463

IS - 4

M1 - bbaa352

ER -