PHLOWER leverages single-cell multimodal data to infer complex, multi-branching cell differentiation trajectories
Nature Methods, vol. 22, pp. 2328–2336
Abstract
Computational trajectory analysis is a key computational task for inferring differentiation trees from this single-cell data. An open challenge is the prediction of complex and multi-branching trees from multimodal data. To address these challenges, we present PHLOWER (decomposition of the Hodge Laplacian for inferring trajectories from flows of cell differentiation), which leverages the harmonic component of the Hodge decomposition on simplicial complexes to infer trajectory embeddings from single-cell multimodal data. These natural representations of cell differentiation facilitate the estimation of their underlying differentiation trees. We evaluate PHLOWER through benchmarking with multi-branching differentiation trees and using kidney organoid multimodal and spatial single-cell data. These demonstrate the power of PHLOWER in both the inference of complex trees and the identification of transcription factors regulating off-target cells in kidney organoids. Thus, PHLOWER enables inference of complex branching trajectories and prediction of transcriptional regulators by leveraging multimodal data.
Authors 12
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Affiliation as printed
Center for Computational Life Sciences, RWTH Aachen University, Aachen, Germany
Institute for Computational Genomics, RWTH Aachen University, Aachen, Germany
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Jitske Jansen Aachen Department of Medicine 2 (Nephrology Clinical Immunology and Hypertension) Institute for Experimental Internal Medicine and Systems Biology
Affiliation as printed
Department of Medicine 2 (Nephrology, Rheumatology, Clinical Immunology and Hypertension), RWTH Aachen University Medical Faculty, Aachen, Germany
Institute for Experimental Internal Medicine and Systems Biology, RWTH Aachen University, Aachen, Germany
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Katharina C. Reimer Aachen Department of Medicine 2 (Nephrology Clinical Immunology and Hypertension) Institute for Experimental Internal Medicine and Systems Biology
Affiliation as printed
Department of Medicine 2 (Nephrology, Rheumatology, Clinical Immunology and Hypertension), RWTH Aachen University Medical Faculty, Aachen, Germany
Institute for Experimental Internal Medicine and Systems Biology, RWTH Aachen University, Aachen, Germany
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Affiliation as printed
Department of Computer Science, RWTH Aachen University, Aachen, Germany
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James Shiniti Nagai Aachen Center for Computational Life Sciences Institute for Computational Genomics
Affiliation as printed
Center for Computational Life Sciences, RWTH Aachen University, Aachen, Germany
Institute for Computational Genomics, RWTH Aachen University, Aachen, Germany
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Broad Institute · Massachusetts General Hospital · Massachusetts Institute of Technology
Affiliation as printed
Gene Regulation Observatory, The Broad Institute of Harvard and MIT, Cambridge, MA, USA
Molecular Pathology Unit, Krantz Family Center for Cancer Research, Massachusetts General Hospital, Boston, MA, USA
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Affiliation as printed
Institute for Experimental Internal Medicine and Systems Biology, RWTH Aachen University, Aachen, Germany
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Affiliation as printed
Center for Computational Life Sciences, RWTH Aachen University, Aachen, Germany
Institute for Computational Genomics, RWTH Aachen University, Aachen, Germany
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Affiliation as printed
Institute for Experimental Internal Medicine and Systems Biology, RWTH Aachen University, Aachen, Germany
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Affiliation as printed
Center for Computational Life Sciences, RWTH Aachen University, Aachen, Germany
Department of Computer Science, RWTH Aachen University, Aachen, Germany
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Rafael Kramann corresponding Aachen Center for Computational Life Sciences Department of Medicine 2 (Nephrology Clinical Immunology and Hypertension) Institute for Experimental Internal Medicine and Systems Biology
Erasmus MC · RWTH Aachen University
Affiliation as printed
Center for Computational Life Sciences, RWTH Aachen University, Aachen, Germany. rkramann@ukaachen.de
Department of Internal Medicine, Nephrology and Transplantation, Erasmus Medical Center, Rotterdam, the Netherlands. rkramann@ukaachen.de
Department of Medicine 2 (Nephrology, Rheumatology, Clinical Immunology and Hypertension), RWTH Aachen University Medical Faculty, Aachen, Germany. rkramann@ukaachen.de
Institute for Experimental Internal Medicine and Systems Biology, RWTH Aachen University, Aachen, Germany. rkramann@ukaachen.de
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Ivan G. Costa corresponding Aachen Center for Computational Life Sciences Institute for Computational Genomics
Affiliation as printed
Center for Computational Life Sciences, RWTH Aachen University, Aachen, Germany. ivan.costa@rwth-aachen.de
Institute for Computational Genomics, RWTH Aachen University, Aachen, Germany. ivan.costa@rwth-aachen.de
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