Enhancing gene regulatory network inference through data integration with markov random fields

Banf, Michael; Rhee, Seung Y.

doi:10.1038/srep41174

Title: Enhancing gene regulatory network inference through data integration with markov random fields

Journal Article · Wed Feb 01 00:00:00 EST 2017 · Scientific Reports

DOI:https://doi.org/10.1038/srep41174· OSTI ID:1347425

Banf, Michael ^[1]; Rhee, Seung Y. ^[1]

Carnegie Institution for Science, Stanford, CA (United States)

Here, a gene regulatory network links transcription factors to their target genes and represents a map of transcriptional regulation. Much progress has been made in deciphering gene regulatory networks computationally. However, gene regulatory network inference for most eukaryotic organisms remain challenging. To improve the accuracy of gene regulatory network inference and facilitate candidate selection for experimentation, we developed an algorithm called GRACE (Gene Regulatory network inference ACcuracy Enhancement). GRACE exploits biological a priori and heterogeneous data integration to generate high- confidence network predictions for eukaryotic organisms using Markov Random Fields in a semi-supervised fashion. GRACE uses a novel optimization scheme to integrate regulatory evidence and biological relevance. It is particularly suited for model learning with sparse regulatory gold standard data. We show GRACE’s potential to produce high confidence regulatory networks compared to state of the art approaches using Drosophila melanogaster and Arabidopsis thaliana data. In an A. thaliana developmental gene regulatory network, GRACE recovers cell cycle related regulatory mechanisms and further hypothesizes several novel regulatory links, including a putative control mechanism of vascular structure formation due to modifications in cell proliferation.

View Accepted Manuscript (DOE)

Cite

Export

Save

Research Organization:: Donald Danforth Plant Science Center, St. Louis, MO (United States)

Sponsoring Organization:: USDOE Office of Science (SC)

Grant/Contract Number:: SC0008769

OSTI ID:: 1347425

Journal Information:: Scientific Reports, Vol. 7; ISSN 2045-2322

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: English

Citation Metrics:

Cited by: 29 works

Citation information provided by
Web of Science

References (66)

Inferring Regulatory Networks from Expression Data Using Tree-Based Methods Huynh-Thu, Vân Anh; Irrthum, Alexandre; Wehenkel, Louis PLoS ONE, Vol. 5, Issue 9 https://doi.org/10.1371/journal.pone.0012776	journal	September 2010
Integrative random forest for gene regulatory network inference Petralia, Francesca; Wang, Pei; Yang, Jialiang Bioinformatics, Vol. 31, Issue 12 https://doi.org/10.1093/bioinformatics/btv268	journal	June 2015
PXY, a Receptor-like Kinase Essential for Maintaining Polarity during Plant Vascular-Tissue Development Fisher, Kate; Turner, Simon Current Biology, Vol. 17, Issue 12 https://doi.org/10.1016/j.cub.2007.05.049	journal	June 2007
Inference of Transcriptional Networks in Arabidopsis through Conserved Noncoding Sequence Analysis de Velde, Jan Van; Heyndrickx, Ken S.; Vandepoele, Klaas The Plant Cell, Vol. 26, Issue 7 https://doi.org/10.1105/tpc.114.127001	journal	July 2014
cMonkey ₂ : Automated, systematic, integrated detection of co-regulated gene modules for any organism Reiss, David J.; Plaisier, Christopher L.; Wu, Wei-Ju Nucleic Acids Research, Vol. 43, Issue 13 https://doi.org/10.1093/nar/gkv300	journal	April 2015
MetaCyc and AraCyc. Metabolic Pathway Databases for Plant Research Zhang, Peifen; Foerster, Hartmut; Tissier, Christophe P. Plant Physiology, Vol. 138, Issue 1 https://doi.org/10.1104/pp.105.060376	journal	May 2005
Manipulation of plant metabolic pathways by transcription factors Iwase, Akira; Matsui, Kyoko; Ohme-Takagi, Masaru Plant Biotechnology, Vol. 26, Issue 1 https://doi.org/10.5511/plantbiotechnology.26.29	journal	January 2009
Network motifs: theory and experimental approaches Alon, Uri Nature Reviews Genetics, Vol. 8, Issue 6 https://doi.org/10.1038/nrg2102	journal	June 2007
BRANE Cut: biologically-related a priori network enhancement with graph cuts for gene regulatory network inference Pirayre, Aurélie; Couprie, Camille; Bidard, Frédérique BMC Bioinformatics, Vol. 16, Issue 1 https://doi.org/10.1186/s12859-015-0754-2	journal	November 2015
Determination and Inference of Eukaryotic Transcription Factor Sequence Specificity Weirauch, Matthew T.; Yang, Ally; Albu, Mihai Cell, Vol. 158, Issue 6 https://doi.org/10.1016/j.cell.2014.08.009	journal	September 2014
SUBA3: a database for integrating experimentation and prediction to define the SUBcellular location of proteins in Arabidopsis Tanz, Sandra K.; Castleden, Ian; Hooper, Cornelia M. Nucleic Acids Research, Vol. 41, Issue D1 https://doi.org/10.1093/nar/gks1151	journal	November 2012
Cell Type-Specific Role of the Retinoblastoma/E2F Pathway during Arabidopsis Leaf Development Desvoyes, Bénédicte; Ramirez-Parra, Elena; Xie, Qi Plant Physiology, Vol. 140, Issue 1 https://doi.org/10.1104/pp.105.071027	journal	December 2005
Transcriptional Regulation and Its Misregulation in Disease Lee, Tong Ihn; Young, Richard A. Cell, Vol. 152, Issue 6 https://doi.org/10.1016/j.cell.2013.02.014	journal	March 2013
AINTEGUMENTA and AINTEGUMENTA-LIKE6 Act Redundantly to Regulate Arabidopsis Floral Growth and Patterning Krizek, BethA. Plant Physiology, Vol. 150, Issue 4 https://doi.org/10.1104/pp.109.141119	journal	June 2009
FlyNet: a versatile network prioritization server for the Drosophila community Shin, Junha; Yang, Sunmo; Kim, Eiru Nucleic Acids Research, Vol. 43, Issue W1 https://doi.org/10.1093/nar/gkv453	journal	May 2015
Regulation of Jasmonate-Mediated Stamen Development and Seed Production by a bHLH-MYB Complex in Arabidopsis Qi, Tiancong; Huang, Huang; Song, Susheng The Plant Cell, Vol. 27, Issue 6 https://doi.org/10.1105/tpc.15.00116	journal	May 2015
Integrated Module and Gene-Specific Regulatory Inference Implicates Upstream Signaling Networks Roy, Sushmita; Lagree, Stephen; Hou, Zhonggang PLoS Computational Biology, Vol. 9, Issue 10 https://doi.org/10.1371/journal.pcbi.1003252	journal	October 2013
The MCM-Binding Protein ETG1 Aids Sister Chromatid Cohesion Required for Postreplicative Homologous Recombination Repair Takahashi, Naoki; Quimbaya, Mauricio; Schubert, Veit PLoS Genetics, Vol. 6, Issue 1 https://doi.org/10.1371/journal.pgen.1000817	journal	January 2010
Supervised, semi-supervised and unsupervised inference of gene regulatory networks Maetschke, S. R.; Madhamshettiwar, P. B.; Davis, M. J. Briefings in Bioinformatics, Vol. 15, Issue 2 https://doi.org/10.1093/bib/bbt034	journal	May 2013
Genome-Wide Analysis of the Core DNA Replication Machinery in the Higher Plants Arabidopsis and Rice Shultz, Randall W.; Tatineni, Vinaya M.; Hanley-Bowdoin, Linda Plant Physiology, Vol. 144, Issue 4 https://doi.org/10.1104/pp.107.101105	journal	June 2007
An empirical Bayes approach to inferring large-scale gene association networks Schafer, J.; Strimmer, K. Bioinformatics, Vol. 21, Issue 6 https://doi.org/10.1093/bioinformatics/bti062	journal	October 2004
Towards revealing the functions of all genes in plants Rhee, Seung Yon; Mutwil, Marek Trends in Plant Science, Vol. 19, Issue 4 https://doi.org/10.1016/j.tplants.2013.10.006	journal	April 2014
Plant organ size control: AINTEGUMENTA regulates growth and cell numbers during organogenesis Mizukami, Y.; Fischer, R. L. Proceedings of the National Academy of Sciences, Vol. 97, Issue 2 https://doi.org/10.1073/pnas.97.2.942	journal	January 2000
Genome-wide transcription factor binding: beyond direct target regulation MacQuarrie, Kyle L.; Fong, Abraham P.; Morse, Randall H. Trends in Genetics, Vol. 27, Issue 4 https://doi.org/10.1016/j.tig.2011.01.001	journal	April 2011
Modification of cell proliferation patterns alters leaf vein architecture in Arabidopsis thaliana Kang, Julie; Mizukami, Yukiko; Wang, Hong Planta, Vol. 226, Issue 5 https://doi.org/10.1007/s00425-007-0567-2	journal	June 2007
Multilayered Organization of Jasmonate Signalling in the Regulation of Root Growth Gasperini, Debora; Chételat, Aurore; Acosta, Ivan F. PLOS Genetics, Vol. 11, Issue 6 https://doi.org/10.1371/journal.pgen.1005300	journal	June 2015
The E2FD/DEL2 factor is a component of a regulatory network controlling cell proliferation and development in Arabidopsis Sozzani, Rosangela; Maggio, Caterina; Giordo, Roberta Plant Molecular Biology, Vol. 72, Issue 4-5 https://doi.org/10.1007/s11103-009-9577-8	journal	November 2009
Evolution of crop species: genetics of domestication and diversification Meyer, Rachel S.; Purugganan, Michael D. Nature Reviews Genetics, Vol. 14, Issue 12 https://doi.org/10.1038/nrg3605	journal	November 2013
The relationship between Precision-Recall and ROC curves Davis, Jesse; Goadrich, Mark Proceedings of the 23rd international conference on Machine learning - ICML '06 https://doi.org/10.1145/1143844.1143874	conference	January 2006
Transcription factors: from enhancer binding to developmental control Spitz, François; Furlong, Eileen E. M. Nature Reviews Genetics, Vol. 13, Issue 9 https://doi.org/10.1038/nrg3207	journal	August 2012
Arabidopsis VIM Proteins Regulate Epigenetic Silencing by Modulating DNA Methylation and Histone Modification in Cooperation with MET1 Kim, Jeongsik; Kim, Jin Hee; Richards, Eric J. Molecular Plant, Vol. 7, Issue 9 https://doi.org/10.1093/mp/ssu079	journal	September 2014
Measuring the wisdom of the crowds in network-based gene function inference Verleyen, W.; Ballouz, S.; Gillis, J. Bioinformatics, Vol. 31, Issue 5 https://doi.org/10.1093/bioinformatics/btu715	journal	October 2014
Gene regulatory networks in plants: learning causality from time and perturbation Krouk, Gabriel; Lingeman, Jesse; Colon, Amy Marshall Genome Biology, Vol. 14, Issue 6 https://doi.org/10.1186/gb-2013-14-6-123	journal	June 2013
Wisdom of crowds for robust gene network inference Marbach, Daniel; Costello, James C.; Küffner, Robert Nature Methods, Vol. 9, Issue 8 https://doi.org/10.1038/nmeth.2016	journal	July 2012
Shortest Connection Networks And Some Generalizations Prim, R. C. Bell System Technical Journal, Vol. 36, Issue 6 https://doi.org/10.1002/j.1538-7305.1957.tb01515.x	journal	November 1957
The JAZ Proteins: A Crucial Interface in the Jasmonate Signaling Cascade Pauwels, Laurens; Goossens, Alain The Plant Cell, Vol. 23, Issue 9 https://doi.org/10.1105/tpc.111.089300	journal	September 2011
Gene Networks in Plant Biology: Approaches in Reconstruction and Analysis Li, Yupeng; Pearl, Stephanie A.; Jackson, Scott A. Trends in Plant Science, Vol. 20, Issue 10 https://doi.org/10.1016/j.tplants.2015.06.013	journal	October 2015
Auxin-Dependent Cell Cycle Reactivation through Transcriptional Regulation of Arabidopsis E2Fa by Lateral Organ Boundary Proteins Berckmans, Barbara; Vassileva, Valya; Schmid, Stephan P. C. The Plant Cell, Vol. 23, Issue 10 https://doi.org/10.1105/tpc.111.088377	journal	October 2011
Molecular Control of Cell Specification and Cell Differentiation During Procambial Development Furuta, Kaori Miyashima; Hellmann, Eva; Helariutta, Ykä Annual Review of Plant Biology, Vol. 65, Issue 1 https://doi.org/10.1146/annurev-arplant-050213-040306	journal	April 2014
Transcriptomic Characterization of a Synergistic Genetic Interaction during Carpel Margin Meristem Development in Arabidopsis thaliana Wynn, April N.; Rueschhoff, Elizabeth E.; Franks, Robert G. PLoS ONE, Vol. 6, Issue 10 https://doi.org/10.1371/journal.pone.0026231	journal	October 2011
Predictive regulatory models in Drosophila melanogaster by integrative inference of transcriptional networks Marbach, D.; Roy, S.; Ay, F. Genome Research, Vol. 22, Issue 7 https://doi.org/10.1101/gr.127191.111	journal	March 2012
Network biology: understanding the cell's functional organization Barabási, Albert-László; Oltvai, Zoltán N. Nature Reviews Genetics, Vol. 5, Issue 2 https://doi.org/10.1038/nrg1272	journal	February 2004
Man made structure detection and verification of object recognition in images for the visually impaired Banf, Michael; Blanz, Volker Proceedings of the 6th International Conference on Computer Vision / Computer Graphics Collaboration Techniques and Applications - MIRAGE '13 https://doi.org/10.1145/2466715.2466732	conference	January 2013
DNA-binding specificities of plant transcription factors and their potential to define target genes Franco-Zorrilla, José M.; López-Vidriero, Irene; Carrasco, José L. Proceedings of the National Academy of Sciences, Vol. 111, Issue 6 https://doi.org/10.1073/pnas.1316278111	journal	January 2014
A Generic Tool for Transcription Factor Target Gene Discovery in Arabidopsis Cell Suspension Cultures Based on Tandem Chromatin Affinity Purification Verkest, Aurine; Abeel, Thomas; Heyndrickx, Ken S. Plant Physiology, Vol. 164, Issue 3 https://doi.org/10.1104/pp.113.229617	journal	January 2014
MYC2: The Master in Action Kazan, Kemal; Manners, John M. Molecular Plant, Vol. 6, Issue 3 https://doi.org/10.1093/mp/sss128	journal	May 2013
Inferring gene regulatory networks by ANOVA Küffner, Robert; Petri, Tobias; Tavakkolkhah, Pegah Bioinformatics, Vol. 28, Issue 10 https://doi.org/10.1093/bioinformatics/bts143	journal	March 2012
B-GATA transcription factors – insights into their structure, regulation, and role in plant development Behringer, Carina; Schwechheimer, Claus Frontiers in Plant Science, Vol. 6 https://doi.org/10.3389/fpls.2015.00090	journal	February 2015
AraNet v2: an improved database of co-functional gene networks for the study of Arabidopsis thaliana and 27 other nonmodel plant species Lee, Tak; Yang, Sunmo; Kim, Eiru Nucleic Acids Research, Vol. 43, Issue D1 https://doi.org/10.1093/nar/gku1053	journal	October 2014
Mutation of the Arabidopsis Calmodulin-Like Protein CML37 Deregulates the Jasmonate Pathway and Enhances Susceptibility to Herbivory Scholz, Sandra S.; Vadassery, Jyothilakshmi; Heyer, Monika Molecular Plant, Vol. 7, Issue 12 https://doi.org/10.1093/mp/ssu102	journal	December 2014
Identification of putative cancer genes through data integration and comparative genomics between plants and humans Quimbaya, Mauricio; Vandepoele, Klaas; Raspé, Eric Cellular and Molecular Life Sciences, Vol. 69, Issue 12 https://doi.org/10.1007/s00018-011-0909-x	journal	January 2012
A gene expression map of Arabidopsis thaliana development Schmid, Markus; Davison, Timothy S.; Henz, Stefan R. Nature Genetics, Vol. 37, Issue 5 https://doi.org/10.1038/ng1543	journal	April 2005
Revealing strengths and weaknesses of methods for gene network inference Marbach, D.; Prill, R. J.; Schaffter, T. Proceedings of the National Academy of Sciences, Vol. 107, Issue 14 https://doi.org/10.1073/pnas.0913357107	journal	March 2010
Large-Scale Mapping and Validation of Escherichia coli Transcriptional Regulation from a Compendium of Expression Profiles Faith, Jeremiah J.; Hayete, Boris; Thaden, Joshua T. PLoS Biology, Vol. 5, Issue 1 https://doi.org/10.1371/journal.pbio.0050008	journal	January 2007
JASPAR 2016: a major expansion and update of the open-access database of transcription factor binding profiles Mathelier, Anthony; Fornes, Oriol; Arenillas, David J. Nucleic Acids Research, Vol. 44, Issue D1 https://doi.org/10.1093/nar/gkv1176	journal	November 2015
Optimization by Simulated Annealing Kirkpatrick, S.; Gelatt, C. D.; Vecchi, M. P. Science, Vol. 220, Issue 4598 https://doi.org/10.1126/science.220.4598.671	journal	May 1983
An Arabidopsis Transcriptional Regulatory Map Reveals Distinct Functional and Evolutionary Features of Novel Transcription Factors Jin, Jinpu; He, Kun; Tang, Xing Molecular Biology and Evolution, Vol. 32, Issue 7 https://doi.org/10.1093/molbev/msv058	journal	March 2015
Advantages and limitations of current network inference methods De Smet, Riet; Marchal, Kathleen Nature Reviews Microbiology, Vol. 8, Issue 10 https://doi.org/10.1038/nrmicro2419	journal	August 2010
A Principled Deep Random Field Model for Image Segmentation Kohli, Pushmeet; Osokin, Anton; Jegelka, Stefanie 2013 IEEE Conference on Computer Vision and Pattern Recognition (CVPR) https://doi.org/10.1109/CVPR.2013.257	conference	June 2013
Random Forests Breiman, Leo Machine Learning, Vol. 45, Issue 1, p. 5-32 https://doi.org/10.1023/A:1010933404324	journal	January 2001
miRNALoc: predicting miRNA subcellular localizations based on principal component scores of physico-chemical properties and pseudo compositions of di-nucleotides Meher, Prabina Kumar; Satpathy, Subhrajit; Rao, Atmakuri Ramakrishna Scientific Reports, Vol. 10, Issue 1 https://doi.org/10.1038/s41598-020-71381-4	journal	September 2020
An Arabidopsis Transcriptional Regulatory Map Reveals Distinct Functional and Evolutionary Features of Novel Transcription Factors [Correction] Molecular Biology and Evolution, Vol. 34, Issue 11, p. 3039 https://doi.org/10.1093/molbev/msx245	journal	October 2017
BRANE Cut: Biologically-Related A priori Network Enhancement with Graph cuts for Gene Regulatory Network Inference Pirayre, Aurélie; Couprie, Camille; Bidard, Frédérique https://doi.org/10.1101/032383	posted_content	November 2015
Revealing strengths and weaknesses of methods for gene network inference Marbach, D.; Prill, R.; Schaffter, T. National Academy of Sciences https://doi.org/10.5167/uzh-39548	text	January 2010
Plant Development: PXY and Polar Cell Division in the Procambium Sieburth, Leslie E. Current Biology, Vol. 17, Issue 15 https://doi.org/10.1016/j.cub.2007.05.066	journal	August 2007
Novel functional roles for PERIANTHIA and SEUSS during floral organ identity specification, floral meristem termination, and gynoecial development Wynn, April N.; Seaman, Andrew A.; Jones, Ashley L. Frontiers in Plant Science, Vol. 5 https://doi.org/10.3389/fpls.2014.00130	journal	April 2014

Cited By (5)

Distinct tissue-specific transcriptional regulation revealed by gene regulatory networks in maize Huang, Ji; Zheng, Juefei; Yuan, Hui BMC Plant Biology, Vol. 18, Issue 1 https://doi.org/10.1186/s12870-018-1329-y	journal	June 2018
Reprogramming of regulatory network using expression uncovers sex-specific gene regulation in Drosophila Wang, Yijie; Cho, Dong-Yeon; Lee, Hangnoh Nature Communications, Vol. 9, Issue 1 https://doi.org/10.1038/s41467-018-06382-z	journal	October 2018
BINDER: computationally inferring a gene regulatory network for Mycobacterium abscessus Staunton, Patrick M.; Miranda-CasoLuengo, Aleksandra A.; Loftus, Brendan J. BMC Bioinformatics, Vol. 20, Issue 1 https://doi.org/10.1186/s12859-019-3042-8	journal	September 2019
Integrative approaches to reconstruct regulatory networks from multi-omics data: A review of state-of-the-art methods Wani, Nisar; Raza, Khalid Computational Biology and Chemistry, Vol. 83 https://doi.org/10.1016/j.compbiolchem.2019.107120	journal	December 2019
Statistical and Machine Learning Approaches to Predict Gene Regulatory Networks From Transcriptome Datasets Mochida, Keiichi; Koda, Satoru; Inoue, Komaki Frontiers in Plant Science, Vol. 9 https://doi.org/10.3389/fpls.2018.01770	journal	November 2018

Similar Records

Systematic discovery of novel eukaryotic transcriptional regulators using sequence homology independent prediction

Journal Article · Mon Jun 26 00:00:00 EDT 2017 · BMC Genomics · OSTI ID:1347425

Bossi, Flavia; Fan, Jue; Xiao, Jun; +5 more

Identification of functional elements and regulatory circuits by Drosophila modENCODE

Journal Article · Wed Dec 22 00:00:00 EST 2010 · Science · OSTI ID:1347425

Roy, Sushmita; Ernst, Jason; Kharchenko, Peter V; +93 more

Combining inferred regulatory and reconstructed metabolic networks enhances phenotype prediction in yeast

Journal Article · Wed May 17 00:00:00 EDT 2017 · PLoS Computational Biology (Online) · OSTI ID:1347425

Wang, Zhuo; Danziger, Samuel A.; Heavner, Benjamin D.; +9 more

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
97 MATHEMATICS AND COMPUTING
gene regulatory networks
machine learning

Title: Enhancing gene regulatory network inference through data integration with markov random fields

Citation Formats

References (66)

Cited By (5)

Similar Records

Related Subjects