ManiNetCluster: a novel manifold learning approach to reveal the functional links between gene networks
Abstract
BACKGROUND:The coordination of genomic functions is a critical and complex process across biological systems such as phenotypes or states (e.g., time, disease, organism, environmental perturbation). Understanding how the complexity of genomic function relates to these states remains a challenge. To address this, we have developed a novel computational method, ManiNetCluster, which simultaneously aligns and clusters gene networks (e.g., co-expression) to systematically reveal the links of genomic function between different conditions. Specifically, ManiNetCluster employs manifold learning to uncover and match local and non-linear structures among networks, and identifies cross-network functional links. RESULTS:We demonstrated that ManiNetCluster better aligns the orthologous genes from their developmental expression profiles across model organisms than state-of-the-art methods (p-value <2.2×10-16). This indicates the potential non-linear interactions of evolutionarily conserved genes across species in development. Furthermore, we applied ManiNetCluster to time series transcriptome data measured in the green alga Chlamydomonas reinhardtii to discover the genomic functions linking various metabolic processes between the light and dark periods of a diurnally cycling culture. We identified a number of genes putatively regulating processes across each lighting regime. CONCLUSIONS:ManiNetCluster provides a novel computational tool to uncover the genes linking various functions from different networks, providing new insight on how gene functions coordinate acrossmore »
- Authors:
-
[2];
- Stony Brook Univ., NY (United States)
- Brookhaven National Lab. (BNL), Upton, NY (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
- Univ. of Wisconsin, Madison, WI (United States)
- Publication Date:
- Research Org.:
- Brookhaven National Laboratory (BNL), Upton, NY (United States); Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC), Biological and Environmental Research (BER)
- OSTI Identifier:
- 1597250
- Alternate Identifier(s):
- OSTI ID: 1591857
- Report Number(s):
- BNL-213599-2020-JAAM
Journal ID: ISSN 1471-2164
- Grant/Contract Number:
- SC0012704; AC02-05CH11231
- Resource Type:
- Accepted Manuscript
- Journal Name:
- BMC Genomics
- Additional Journal Information:
- Journal Volume: 20; Journal Issue: S12; Conference: The International Conference on Intelligent Biology and Medicine (ICIBM) 2019, Columbus, OH (United States), 9-11 Jun 2019; Journal ID: ISSN 1471-2164
- Publisher:
- Springer
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 97 MATHEMATICS AND COMPUTING; Manifold learning; Manifold regularization; Clustering; Multiview learning; Functional genomics; Comparative network analysis; Comparative genomics; Biofuel
Citation Formats
Nguyen, Nam D., Blaby, Ian K., and Wang, Daifeng. ManiNetCluster: a novel manifold learning approach to reveal the functional links between gene networks. United States: N. p., 2019.
Web. doi:10.1186/s12864-019-6329-2.
Nguyen, Nam D., Blaby, Ian K., & Wang, Daifeng. ManiNetCluster: a novel manifold learning approach to reveal the functional links between gene networks. United States. https://doi.org/10.1186/s12864-019-6329-2
Nguyen, Nam D., Blaby, Ian K., and Wang, Daifeng. Mon .
"ManiNetCluster: a novel manifold learning approach to reveal the functional links between gene networks". United States. https://doi.org/10.1186/s12864-019-6329-2. https://www.osti.gov/servlets/purl/1597250.
@article{osti_1597250,
title = {ManiNetCluster: a novel manifold learning approach to reveal the functional links between gene networks},
author = {Nguyen, Nam D. and Blaby, Ian K. and Wang, Daifeng},
abstractNote = {BACKGROUND:The coordination of genomic functions is a critical and complex process across biological systems such as phenotypes or states (e.g., time, disease, organism, environmental perturbation). Understanding how the complexity of genomic function relates to these states remains a challenge. To address this, we have developed a novel computational method, ManiNetCluster, which simultaneously aligns and clusters gene networks (e.g., co-expression) to systematically reveal the links of genomic function between different conditions. Specifically, ManiNetCluster employs manifold learning to uncover and match local and non-linear structures among networks, and identifies cross-network functional links. RESULTS:We demonstrated that ManiNetCluster better aligns the orthologous genes from their developmental expression profiles across model organisms than state-of-the-art methods (p-value <2.2×10-16). This indicates the potential non-linear interactions of evolutionarily conserved genes across species in development. Furthermore, we applied ManiNetCluster to time series transcriptome data measured in the green alga Chlamydomonas reinhardtii to discover the genomic functions linking various metabolic processes between the light and dark periods of a diurnally cycling culture. We identified a number of genes putatively regulating processes across each lighting regime. CONCLUSIONS:ManiNetCluster provides a novel computational tool to uncover the genes linking various functions from different networks, providing new insight on how gene functions coordinate across different conditions. ManiNetCluster is publicly available as an R package at https://github.com/daifengwanglab/ManiNetCluster.},
doi = {10.1186/s12864-019-6329-2},
journal = {BMC Genomics},
number = S12,
volume = 20,
place = {United States},
year = {Mon Dec 30 00:00:00 EST 2019},
month = {Mon Dec 30 00:00:00 EST 2019}
}
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Works referenced in this record:
Gene co-expression network topology provides a framework for molecular characterization of cellular state
journal, May 2004
- Carter, S. L.; Brechbuhler, C. M.; Griffin, M.
- Bioinformatics, Vol. 20, Issue 14
WGCNA: an R package for weighted correlation network analysis
journal, December 2008
- Langfelder, Peter; Horvath, Steve
- BMC Bioinformatics, Vol. 9, Issue 1
Large-scale prediction of long non-coding RNA functions in a coding–non-coding gene co-expression network
journal, January 2011
- Liao, Qi; Liu, Changning; Yuan, Xiongying
- Nucleic Acids Research, Vol. 39, Issue 9
Gene co-expression network analysis reveals common system-level properties of prognostic genes across cancer types
journal, February 2014
- Yang, Yang; Han, Leng; Yuan, Yuan
- Nature Communications, Vol. 5, Issue 1
A General Framework for Weighted Gene Co-Expression Network Analysis
journal, January 2005
- Zhang, Bin; Horvath, Steve
- Statistical Applications in Genetics and Molecular Biology, Vol. 4, Issue 1
On the selection of appropriate distances for gene expression data clustering
journal, January 2014
- Jaskowiak, Pablo A.; Campello, Ricardo JGB; Costa, Ivan G.
- BMC Bioinformatics, Vol. 15, Issue S2
Cross-Disciplinary Network Comparison: Matchmaking between Hairballs
journal, March 2016
- Yan, Koon-Kiu; Wang, Daifeng; Sethi, Anurag
- Cell Systems, Vol. 2, Issue 3
Gene network interconnectedness and the generalized topological overlap measure
journal, January 2007
- Yip, Andy M.; Horvath, Steve
- BMC Bioinformatics, Vol. 8, Issue 1
OrthoClust: an orthology-based network framework for clustering data across multiple species
journal, January 2014
- Yan, Koon-Kiu; Wang, Daifeng; Rozowsky, Joel
- Genome Biology, Vol. 15, Issue 8
OrthoCluster: a new tool for mining synteny blocks and applications in comparative genomics
conference, January 2008
- Zeng, Xinghuo; Nesbitt, Matthew J.; Pei, Jian
- Proceedings of the 11th international conference on Extending database technology Advances in database technology - EDBT '08
A human B‐cell interactome identifies MYB and FOXM1 as master regulators of proliferation in germinal centers
journal, January 2010
- Lefebvre, Celine; Rajbhandari, Presha; Alvarez, Mariano J.
- Molecular Systems Biology, Vol. 6, Issue 1
A global view of genomic information – moving beyond the gene and the master regulator
journal, January 2010
- Mattick, John S.; Taft, Ryan J.; Faulkner, Geoffrey J.
- Trends in Genetics, Vol. 26, Issue 1
Simultaneous Clustering of Multiple Gene Expression and Physical Interaction Datasets
journal, April 2010
- Narayanan, Manikandan; Vetta, Adrian; Schadt, Eric E.
- PLoS Computational Biology, Vol. 6, Issue 4
MAGNA: Maximizing Accuracy in Global Network Alignment
journal, July 2014
- Saraph, Vikram; Milenković, Tijana
- Bioinformatics, Vol. 30, Issue 20
MAGNA++: Maximizing Accuracy in Global Network Alignment via both node and edge conservation
journal, March 2015
- Vijayan, V.; Saraph, V.; Milenković, T.
- Bioinformatics, Vol. 31, Issue 14
PrimAlign: PageRank-inspired Markovian alignment for large biological networks
journal, June 2018
- Kalecky, Karel; Cho, Young-Rae
- Bioinformatics, Vol. 34, Issue 13
IsoRankN: spectral methods for global alignment of multiple protein networks
journal, May 2009
- Liao, C. -S.; Lu, K.; Baym, M.
- Bioinformatics, Vol. 25, Issue 12
Global alignment of multiple protein interaction networks with application to functional orthology detection
journal, August 2008
- Singh, R.; Xu, J.; Berger, B.
- Proceedings of the National Academy of Sciences, Vol. 105, Issue 35
An RKHS for multi-view learning and manifold co-regularization
conference, January 2008
- Sindhwani, Vikas; Rosenberg, David S.
- Proceedings of the 25th international conference on Machine learning - ICML '08
REGAL: Representation Learning-based Graph Alignment
conference, January 2018
- Heimann, Mark; Shen, Haoming; Safavi, Tara
- Proceedings of the 27th ACM International Conference on Information and Knowledge Management - CIKM '18
Representation Learning: A Review and New Perspectives
journal, August 2013
- Bengio, Y.; Courville, A.; Vincent, P.
- IEEE Transactions on Pattern Analysis and Machine Intelligence, Vol. 35, Issue 8
Laplacian Eigenmaps for Dimensionality Reduction and Data Representation
journal, June 2003
- Belkin, Mikhail; Niyogi, Partha
- Neural Computation, Vol. 15, Issue 6
Alignment of single-cell trajectories to compare cellular expression dynamics
journal, March 2018
- Alpert, Ayelet; Moore, Lindsay S.; Dubovik, Tania
- Nature Methods, Vol. 15, Issue 4
MATCHER: manifold alignment reveals correspondence between single cell transcriptome and epigenome dynamics
journal, July 2017
- Welch, Joshua D.; Hartemink, Alexander J.; Prins, Jan F.
- Genome Biology, Vol. 18, Issue 1
Testing the manifold hypothesis
journal, February 2016
- Fefferman, Charles; Mitter, Sanjoy; Narayanan, Hariharan
- Journal of the American Mathematical Society, Vol. 29, Issue 4
Recovering the number of clusters in data sets with noise features using feature rescaling factors
journal, December 2015
- de Amorim, Renato Cordeiro; Hennig, Christian
- Information Sciences, Vol. 324
The Application of Cluster Analysis in Strategic Management Research: an Analysis and Critique
journal, June 1996
- KETCHEN Jr., David J.; Shook, Christopher L.
- Strategic Management Journal, Vol. 17, Issue 6
Unlocking the secrets of the genome
journal, June 2009
- Celniker, Susan E.; Dillon, Laura A. L.; Gerstein, Mark B.
- Nature, Vol. 459, Issue 7249
Skeletal representations of orthogonal shapes
journal, July 2013
- Martínez, Jonàs; Pla, Núria; Vigo, Marc
- Graphical Models, Vol. 75, Issue 4
Proteomic analysis of a eukaryotic cilium
journal, July 2005
- Pazour, Gregory J.; Agrin, Nathan; Leszyk, John
- The Journal of Cell Biology, Vol. 170, Issue 1
The GreenCut: re-evaluation of physiological role of previously studied proteins and potential novel protein functions
journal, July 2013
- Heinnickel, Mark L.; Grossman, Arthur R.
- Photosynthesis Research, Vol. 116, Issue 2-3
The GreenCut2 Resource, a Phylogenomically Derived Inventory of Proteins Specific to the Plant Lineage
journal, April 2011
- Karpowicz, Steven J.; Prochnik, Simon E.; Grossman, Arthur R.
- Journal of Biological Chemistry, Vol. 286, Issue 24
The Chlamydomonas Genome Reveals the Evolution of Key Animal and Plant Functions
journal, October 2007
- Merchant, S. S.; Prochnik, S. E.; Vallon, O.
- Science, Vol. 318, Issue 5848, p. 245-250
Assembly of the Light-Harvesting Chlorophyll Antenna in the Green Alga Chlamydomonas reinhardtii Requires Expression of the TLA2 - CpFTSY Gene
journal, November 2011
- Kirst, Henning; García-Cerdán, Jose Gines; Zurbriggen, Andreas
- Plant Physiology, Vol. 158, Issue 2
Evolution of Chlamydomonas reinhardtii ferredoxins and their interactions with [FeFe]-hydrogenases
journal, June 2017
- Sawyer, Anne; Winkler, Martin
- Photosynthesis Research, Vol. 134, Issue 3
A survey of multi-view machine learning
journal, February 2013
- Sun, Shiliang
- Neural Computing and Applications, Vol. 23, Issue 7-8
Statistical single cell multi-omics integration
journal, February 2018
- Colomé-Tatché, M.; Theis, F. J.
- Current Opinion in Systems Biology, Vol. 7
Latent periodic process inference from single-cell RNA-seq data
journal, March 2020
- Liang, Shaoheng; Wang, Fang; Han, Jincheng
- Nature Communications, Vol. 11, Issue 1
Transcriptional profiling of two contrasting genotypes uncovers molecular mechanisms underlying salt tolerance in alfalfa
journal, March 2021
- Kaundal, Rakesh; Duhan, Naveen; Acharya, Biswa R.
- Scientific Reports, Vol. 11, Issue 1
Unlocking the secrets of the genome
text, January 2009
- P., White, Kevin; Steven, Henikoff,; Fabio, Piano,
- The University of North Carolina at Chapel Hill University Libraries
On the selection of appropriate distances for gene expression data clustering
text, January 2014
- Jaskowiak, Pablo A.; Campello, Ricardo J. G. B.; Costa, Ivan G.
- RWTH Aachen University
A human B-cell interactome identifies MYB and FOXM1 as master regulators of proliferation in germinal centers
text, January 2010
- Celine, Lefebvre,; Presha, Rajbhandari,; J., Alvarez, Mariano
- ETH Zurich
Representation Learning: A Review and New Perspectives
preprint, January 2012
- Bengio, Yoshua; Courville, Aaron; Vincent, Pascal
- arXiv
Testing the Manifold Hypothesis
preprint, January 2013
- Fefferman, Charles; Mitter, Sanjoy; Narayanan, Hariharan
- arXiv
MAGNA: Maximizing Accuracy in Global Network Alignment
preprint, January 2013
- Saraph, Vikram; Milenković, Tijana
- arXiv
REGAL: Representation Learning-based Graph Alignment
text, January 2018
- Heimann, Mark; Shen, Haoming; Safavi, Tara
- arXiv
Voluntary exposure to a toxin: the genetic influence on ethanol consumption
journal, December 2017
- Hoffman, Paula L.; Saba, Laura M.; Vanderlinden, Lauren A.
- Mammalian Genome, Vol. 29, Issue 1-2
A survey of multi-view machine learning
journal, February 2013
- Sun, Shiliang
- Neural Computing and Applications, Vol. 23, Issue 7-8
The GreenCut: re-evaluation of physiological role of previously studied proteins and potential novel protein functions
journal, July 2013
- Heinnickel, Mark L.; Grossman, Arthur R.
- Photosynthesis Research, Vol. 116, Issue 2-3
Evolution of Chlamydomonas reinhardtii ferredoxins and their interactions with [FeFe]-hydrogenases
journal, June 2017
- Sawyer, Anne; Winkler, Martin
- Photosynthesis Research, Vol. 134, Issue 3
Cross-Disciplinary Network Comparison: Matchmaking between Hairballs
journal, March 2016
- Yan, Koon-Kiu; Wang, Daifeng; Sethi, Anurag
- Cell Systems, Vol. 2, Issue 3
Statistical single cell multi-omics integration
journal, February 2018
- Colomé-Tatché, M.; Theis, F. J.
- Current Opinion in Systems Biology, Vol. 7
Skeletal representations of orthogonal shapes
journal, July 2013
- Martínez, Jonàs; Pla, Núria; Vigo, Marc
- Graphical Models, Vol. 75, Issue 4
Unlocking the secrets of the genome
journal, June 2009
- Celniker, Susan E.; Dillon, Laura A. L.; Gerstein, Mark B.
- Nature, Vol. 459, Issue 7249
Gene co-expression network analysis reveals common system-level properties of prognostic genes across cancer types
journal, February 2014
- Yang, Yang; Han, Leng; Yuan, Yuan
- Nature Communications, Vol. 5, Issue 1
Alignment of single-cell trajectories to compare cellular expression dynamics
journal, March 2018
- Alpert, Ayelet; Moore, Lindsay S.; Dubovik, Tania
- Nature Methods, Vol. 15, Issue 4
Proteomic analysis of a eukaryotic cilium
journal, July 2005
- Pazour, Gregory J.; Agrin, Nathan; Leszyk, John
- The Journal of Cell Biology, Vol. 170, Issue 1
Gene co-expression network topology provides a framework for molecular characterization of cellular state
journal, May 2004
- Carter, S. L.; Brechbuhler, C. M.; Griffin, M.
- Bioinformatics, Vol. 20, Issue 14
IsoRankN: spectral methods for global alignment of multiple protein networks
journal, May 2009
- Liao, C. -S.; Lu, K.; Baym, M.
- Bioinformatics, Vol. 25, Issue 12
MAGNA++: Maximizing Accuracy in Global Network Alignment via both node and edge conservation
journal, March 2015
- Vijayan, V.; Saraph, V.; Milenković, T.
- Bioinformatics, Vol. 31, Issue 14
Large-scale prediction of long non-coding RNA functions in a coding–non-coding gene co-expression network
journal, January 2011
- Liao, Qi; Liu, Changning; Yuan, Xiongying
- Nucleic Acids Research, Vol. 39, Issue 9
mapman: a user-driven tool to display genomics data sets onto diagrams of metabolic pathways and other biological processes
journal, March 2004
- Thimm, Oliver; Bläsing, Oliver; Gibon, Yves
- The Plant Journal, Vol. 37, Issue 6, p. 914-939
Laplacian Eigenmaps for Dimensionality Reduction and Data Representation
journal, June 2003
- Belkin, Mikhail; Niyogi, Partha
- Neural Computation, Vol. 15, Issue 6
Gene network interconnectedness and the generalized topological overlap measure
journal, January 2007
- Yip, Andy M.; Horvath, Steve
- BMC Bioinformatics, Vol. 8, Issue 1
WGCNA: an R package for weighted correlation network analysis
journal, December 2008
- Langfelder, Peter; Horvath, Steve
- BMC Bioinformatics, Vol. 9, Issue 1
OrthoClust: an orthology-based network framework for clustering data across multiple species
journal, January 2014
- Yan, Koon-Kiu; Wang, Daifeng; Rozowsky, Joel
- Genome Biology, Vol. 15, Issue 8
MATCHER: manifold alignment reveals correspondence between single cell transcriptome and epigenome dynamics
journal, July 2017
- Welch, Joshua D.; Hartemink, Alexander J.; Prins, Jan F.
- Genome Biology, Vol. 18, Issue 1
MAGNA: Maximizing Accuracy in Global Network Alignment
preprint, January 2013
- Saraph, Vikram; Milenković, Tijana
- arXiv
Applying deep learning techniques on medical corpora from the World Wide Web: a prototypical system and evaluation
preprint, January 2015
- Miñarro-Giménez, Jose Antonio; Marín-Alonso, Oscar; Samwald, Matthias
- arXiv