Revealing dynamic temporal trajectories and underlying regulatory networks with Cflows Article Swipe

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Xingzhi Sun , Shabarni Gupta , Shabarni Gupta , Manik Kuchroo , Dhananjay Bhaskar , Laura Rangel , Brandon Zhu , John G. Lock , Laura Rangel , Vanina Rodríguez , John G. Lock , Christine L. Chaffer , Smita Krishnaswamy ·

YOU? · · 2023 · Open Access · · DOI: https://doi.org/10.1101/2023.03.28.534644

While single-cell technologies provide snapshots of tumor states, building continuous trajectories and uncovering causative gene regulatory networks remains a significant challenge. We present Cflows , an AI framework that combines neural ODE networks with Granger causality to infer continuous cell state transitions and gene regulatory interactions from static scRNA-seq data. In a new 5-time point dataset capturing tumorsphere development over 30 days, Cflows reconstructs two types of trajectories leading to tumorsphere formation or apoptosis. Trajectory-based cell-of-origin analysis delineated a novel cancer stem cell profile characterized by CD44 hi EPCAM + CAV1 + , and uncovered a cell cycle–dependent enrichment of tumorsphere-initiating potential in G2/M or S-phase cells. Cflows uncovers ESRRA as a crucial causal driver of the tumor-forming gene regulatory network. Indeed, ESRRA inhibition significantly reduces tumor growth and metastasis in vivo. Cflows offers a powerful framework for uncovering cellular transitions and dynamic regulatory networks from static single-cell data.

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Ode Dynamics (music) Computer science Mathematics Psychology Applied mathematics Pedagogy

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Type: preprint
Language: en
Landing Page: https://doi.org/10.1101/2023.03.28.534644
PDF: https://www.biorxiv.org/content/biorxiv/early/2023/03/29/2023.03.28.534644.full.pdf
OA Status: green
Cited By: 8
References: 56
Related Works: 10
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DOI: https://doi.org/10.1101/2023.03.28.534644

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Title: Revealing dynamic temporal trajectories and underlying regulatory networks with Cflows

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Type: preprint

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Language: en

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Publication year: 2023

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Publication date: 2023-03-29

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Authors: Xingzhi Sun, Shabarni Gupta, Shabarni Gupta, Manik Kuchroo, Dhananjay Bhaskar, Laura Rangel, Brandon Zhu, John G. Lock, Laura Rangel, Vanina Rodríguez, John G. Lock, Christine L. Chaffer, Smita Krishnaswamy

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Landing page: https://doi.org/10.1101/2023.03.28.534644

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Concepts: Ode, Dynamics (music), Computer science, Mathematics, Psychology, Applied mathematics, Pedagogy

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Cited by: 8

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