Incorporating chromatin accessibility data into sequence-to-expression modeling

Biophysical Journal
Pei-Chen PengSaurabh Sinha

Abstract

Prediction of gene expression levels from regulatory sequences is one of the major challenges of genomic biology today. A particularly promising approach to this problem is that taken by thermodynamics-based models that interpret an enhancer sequence in a given cellular context specified by transcription factor concentration levels and predict precise expression levels driven by that enhancer. Such models have so far not accounted for the effect of chromatin accessibility on interactions between transcription factor and DNA and consequently on gene-expression levels. Here, we extend a thermodynamics-based model of gene expression, called GEMSTAT (Gene Expression Modeling Based on Statistical Thermodynamics), to incorporate chromatin accessibility data and quantify its effect on accuracy of expression prediction. In the new model, called GEMSTAT-A, accessibility at a binding site is assumed to affect the transcription factor's binding strength at the site, whereas all other aspects are identical to the GEMSTAT model. We show that this modification results in significantly better fits in a data set of over 30 enhancers regulating spatial expression patterns in the blastoderm-stage Drosophila embryo. It is important to note that t...Continue Reading

References

May 15, 1998·Trends in Biochemical Sciences·G D Stormo, D S Fields
Jul 25, 1998·Science·E M Blackwood, J T Kadonaga
May 17, 2000·Bioinformatics·G D Stormo
Apr 19, 2003·Proceedings of the National Academy of Sciences of the United States of America·Nicolas E BuchlerTerence Hwa
Sep 27, 2003·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Renzo WolboldUlrich M Zanger
Apr 3, 2004·Bioinformatics·Ekaterina PoustelnikovaJohn Reinitz
Nov 20, 2004·Proceedings of the National Academy of Sciences of the United States of America·Peter J SaboJohn A Stamatoyannopoulos
Mar 31, 2005·Current Opinion in Genetics & Development·Lacramioara BintuRob Phillips
Aug 10, 2005·Journal of Pharmaceutical and Biomedical Analysis·Vincenzo Rizzo, Vittorio Pinciroli
Nov 24, 2005·Bioinformatics·Steven M GalloMarc S Halfon
Jun 6, 2006·Current Biology : CB·Robert P ZinzenDmitri Papatsenko
May 16, 2007·PLoS Computational Biology·Robert P Zinzen, Dmitri Papatsenko
Feb 22, 2008·Proceedings of the National Academy of Sciences of the United States of America·Dmitri Papatsenko, Michael S Levine
Oct 28, 2008·Nucleic Acids Research·Andrei PisarevJohn Reinitz
Mar 24, 2009·Nature Methods·Jay R HesselberthJohn A Stamatoyannopoulos
Apr 10, 2009·Annual Review of Biochemistry·Cedric R Clapier, Bradley R Cairns
Jun 10, 2009·Nature Reviews. Genetics·Eran Segal, Jonathan Widom
Jan 21, 2010·Molecular Systems Biology·Walid D FakhouriDavid N Arnosti
Feb 6, 2010·Proceedings of the National Academy of Sciences of the United States of America·Rosa KarlićMartin Vingron
May 17, 2011·Genome Biology·Sean ThomasJohn A Stamatoyannopoulos
Dec 7, 2011·Nature Reviews. Genetics·Patricia J Wittkopp, Gizem Kalay
Aug 22, 2012·Proceedings of the National Academy of Sciences of the United States of America·Thijn van der HeijdenJohn van Noort
Sep 8, 2012·Genome Research·Anirudh NatarajanUwe Ohler
Oct 30, 2012·Trends in Genetics : TIG·J Omar Yáñez-CunaAlexander Stark
Mar 12, 2013·Molecular Cell·Eliezer Calo, Joanna Wysocka
Apr 30, 2013·Methods : a Companion to Methods in Enzymology·Abul Hassan Samee, Saurabh Sinha
Jul 16, 2013·Nature Methods·Stephen S GisselbrechtMartha L Bulyk
Sep 12, 2013·Briefings in Bioinformatics·Hui LiuShuigeng Zhou
Dec 25, 2013·Nature Reviews. Genetics·Taiping Chen, Sharon Y R Dent
Jan 7, 2014·Human Genetics·Shira Weingarten-Gabbay, Eran Segal
Jan 29, 2014·Proceedings of the National Academy of Sciences of the United States of America·Troels T Marstrand, John D Storey

❮ Previous
Next ❯

Citations

Jun 4, 2016·Nucleic Acids Research·Pei-Chen Peng, Saurabh Sinha
Apr 23, 2016·PLoS Computational Biology·Antonio L C Gomes, Harris H Wang
May 23, 2019·Genome Biology and Evolution·Pei-Chen PengSaurabh Sinha
May 7, 2020·Annual Review of Biophysics·Felix Wong, Jeremy Gunawardena
Jul 11, 2018·Ecology and Evolution·Julia B SaltzJason Keagy

❮ Previous
Next ❯

Related Concepts

Related Feeds

Allergy and Asthma

Allergy and asthma are inflammatory disorders that are triggered by the activation of an allergen-specific regulatory t cell. These t cells become activated when allergens are recognized by allergen-presenting cells. Here is the latest research on allergy and asthma.

CREs: Gene & Cell Therapy

Gene and cell therapy advances have shown promising outcomes for several diseases. The role of cis-regulatory elements (CREs) is crucial in the design of gene therapy vectors. Here is the latest research on CREs in gene and cell therapy.