Deep learning connects DNA traces to transcription to reveal predictive features beyond enhancer-promoter contact.

Nature Communications
Aparna R RajpurkarAlistair Boettiger

Abstract

Chromatin architecture plays an important role in gene regulation. Recent advances in super-resolution microscopy have made it possible to measure chromatin 3D structure and transcription in thousands of single cells. However, leveraging these complex data sets with a computationally unbiased method has been challenging. Here, we present a deep learning-based approach to better understand to what degree chromatin structure relates to transcriptional state of individual cells. Furthermore, we explore methods to "unpack the black box" to determine in an unbiased manner which structural features of chromatin regulation are most important for gene expression state. We apply this approach to an Optical Reconstruction of Chromatin Architecture dataset of the Bithorax gene cluster in Drosophila and show it outperforms previous contact-focused methods in predicting expression state from 3D structure. We find the structural information is distributed across the domain, overlapping and extending beyond domains identified by prior genetic analyses. Individual enhancer-promoter interactions are a minor contributor to predictions of activity.

References

May 25, 2004·Genes & Development·Séverine Chambeyron, Wendy A Bickmore
Nov 30, 2004·Science·Nicole J FrancisChristopher L Woodcock
Mar 25, 2006·Development·Robert K Maeda, François Karch
Aug 18, 2006·Current Opinion in Genetics & Development·Jürg Müller, Judith A Kassis
Aug 28, 2010·Current Biology : CB·Michael W PerryMichael Levine
Jan 29, 2011·Chromosome Research : an International Journal on the Molecular, Supramolecular and Evolutionary Aspects of Chromosome Biology·Leonid A Mirny
Aug 10, 2011·Proceedings of the National Academy of Sciences of the United States of America·Michael W PerryMichael Levine
Feb 20, 2013·Advances in Genetics·Judith A Kassis, J Lesley Brown
May 6, 2014·Current Biology : CB·Nimish KhannaAndrew S Belmont
Oct 3, 2014·Cold Spring Harbor Perspectives in Biology·Robert E Kingston, John W Tamkun
Dec 3, 2014·Neural Networks : the Official Journal of the International Neural Network Society·Jürgen Schmidhuber
Jun 13, 2015·Chromosoma·Robert K Maeda, François Karch
Jul 29, 2015·Mechanisms of Development·Olga KyrchanovaPaul Schedl
Oct 28, 2015·Proceedings of the National Academy of Sciences of the United States of America·Pierre J FabreDenis Duboule
Dec 22, 2015·Current Biology : CB·Enrico CannavòEileen E M Furlong
Jan 14, 2016·Nature Communications·Ajazul H WaniNicole J Francis
Apr 19, 2016·Nature Biotechnology·Hanhui MaThoru Pederson
Jul 5, 2016·Nature Genetics·Deborah HayDouglas R Higgs
Sep 1, 2016·IEEE Transactions on Neural Networks and Learning Systems·Wojciech SamekKlaus-Robert Muller
Jan 5, 2017·Genetics·Yuri B Schwartz, Giacomo Cavalli
Mar 25, 2017·Cell·Denes HniszPhillip A Sharp
Jul 27, 2017·PLoS Computational Biology·Peter EastmanVijay S Pande
Aug 9, 2017·Annual Review of Cell and Developmental Biology·Miao Yu, Bing Ren
Sep 25, 2017·Cell·Bernd SchuettengruberGiacomo Cavalli
Feb 9, 2018·Nature·Marco OsterwalderLen A Pennacchio
Mar 6, 2018·Science Advances·Quentin SzaboGiacomo Cavalli
Jul 4, 2018·Proceedings of the National Academy of Sciences of the United States of America·Johannes NueblerLeonid A Mirny
Jul 25, 2018·Nature Genetics·Hongtao ChenThomas Gregor
Sep 29, 2018·Science·Eileen E M Furlong, Michael Levine
Oct 28, 2018·Nature Reviews. Genetics·M Jordan Rowley, Victor G Corces
Nov 1, 2018·Nature Methods·Hanhui MaThoru Pederson

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Software Mentioned

openmm
scikit
stats
Keras
R
RandomForestParamSearchAbdA
MINA
RandomForestClassifier
learn
GradientExplainer

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