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A practical comparison of methods for detecting transcription factor binding sites in ChIP-seq experiments




TekijätLaajala TD, Raghav S, Tuomela S, Lahesmaa R, Aittokallio T, Elo LL

KustantajaBIOMED CENTRAL LTD

Julkaisuvuosi2009

JournalBMC Genomics

Tietokannassa oleva lehden nimiBMC GENOMICS

Lehden akronyymiBMC GENOMICS

Artikkelin numeroARTN 618

Vuosikerta10

Sivujen määrä15

ISSN1471-2164

DOIhttps://doi.org/10.1186/1471-2164-10-618

Verkko-osoitehttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2804666/pdf/1471-2164-10-618.pdf


Tiivistelmä
Background: Chromatin immunoprecipitation coupled with massively parallel sequencing (ChIPseq)
is increasingly being applied to study transcriptional regulation on a genome-wide scale. While
numerous algorithms have recently been proposed for analysing the large ChIP-seq datasets, their
relative merits and potential limitations remain unclear in practical applications.
Results: The present study compares the state-of-the-art algorithms for detecting transcription
factor binding sites in four diverse ChIP-seq datasets under a variety of practical research settings.
First, we demonstrate how the biological conclusions may change dramatically when the different
algorithms are applied. The reproducibility across biological replicates is then investigated as an
internal validation of the detections. Finally, the predicted binding sites with each method are
compared to high-scoring binding motifs as well as binding regions confirmed in independent qPCR
experiments.
Conclusions: In general, our results indicate that the optimal choice of the computational
approach depends heavily on the dataset under analysis. In addition to revealing valuable
information to the users of this technology about the characteristics of the binding site detection
approaches, the systematic evaluation framework provides also a useful reference to the
developers of improved algorithms for ChIP-seq data.

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