Building gene regulatory networks from scATAC-seq and scRNA-seq using Linked Self Organizing Maps
Ramirez, Ricardo N.
El-Ali, Nicole C.
KAUST DepartmentBiological and Environmental Sciences and Engineering (BESE) Division
Permanent link to this recordhttp://hdl.handle.net/10754/660332
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AbstractRapid advances in single-cell assays have outpaced methods for analysis of those data types. Different single-cell assays show extensive variation in sensitivity and signal to noise levels. In particular, scATAC-seq generates extremely sparse and noisy datasets. Existing methods developed to analyze this data require cells amenable to pseudo-time analysis or require datasets with drastically different cell-types. We describe a novel approach using self-organizing maps (SOM) to link scATAC-seq regions with scRNA-seq genes that overcomes these challenges and can generate draft regulatory networks. Our SOMatic package generates chromatin and gene expression SOMs separately and combines them using a linking function. We applied SOMatic on a mouse pre-B cell differentiation time-course using controlled Ikaros over-expression to recover gene ontology enrichments, identify motifs in genomic regions showing similar single-cell profiles, and generate a gene regulatory network that both recovers known interactions and predicts new Ikaros targets during the differentiation process. The ability of linked SOMs to detect emergent properties from multiple types of highly-dimensional genomic data with very different signal properties opens new avenues for integrative analysis of heterogeneous data.
CitationJansen, C., Ramirez, R. N., El-Ali, N. C., Gomez-Cabrero, D., Tegner, J., Merkenschlager, M., … Mortazavi, A. (2019). Building gene regulatory networks from scATAC-seq and scRNA-seq using Linked Self Organizing Maps. PLOS Computational Biology, 15(11), e1006555. doi:10.1371/journal.pcbi.1006555
SponsorsThis work was supported by were supported by EU FP7 306000 STATegra.
PublisherPublic Library of Science (PLoS)
JournalPLoS computational biology
Except where otherwise noted, this item's license is described as Copyright: © 2019 Jansen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.