NETISCE: a network-based tool for cell fate reprogramming

Abstract The search for effective therapeutic targets in fields like regenerative medicine and cancer research has generated interest in cell fate reprogramming. This cellular reprogramming paradigm can drive cells to a desired target state from any initial state. However, methods for identifying re...

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Main Authors: Lauren Marazzi, Milan Shah, Shreedula Balakrishnan, Ananya Patil, Paola Vera-Licona
Format: Article
Language:English
Published: Nature Portfolio 2022-06-01
Series:npj Systems Biology and Applications
Online Access:https://doi.org/10.1038/s41540-022-00231-y
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author Lauren Marazzi
Milan Shah
Shreedula Balakrishnan
Ananya Patil
Paola Vera-Licona
author_facet Lauren Marazzi
Milan Shah
Shreedula Balakrishnan
Ananya Patil
Paola Vera-Licona
author_sort Lauren Marazzi
collection DOAJ
description Abstract The search for effective therapeutic targets in fields like regenerative medicine and cancer research has generated interest in cell fate reprogramming. This cellular reprogramming paradigm can drive cells to a desired target state from any initial state. However, methods for identifying reprogramming targets remain limited for biological systems that lack large sets of experimental data or a dynamical characterization. We present NETISCE, a novel computational tool for identifying cell fate reprogramming targets in static networks. In combination with machine learning algorithms, NETISCE estimates the attractor landscape and predicts reprogramming targets using signal flow analysis and feedback vertex set control, respectively. Through validations in studies of cell fate reprogramming from developmental, stem cell, and cancer biology, we show that NETISCE can predict previously identified cell fate reprogramming targets and identify potentially novel combinations of targets. NETISCE extends cell fate reprogramming studies to larger-scale biological networks without the need for full model parameterization and can be implemented by experimental and computational biologists to identify parts of a biological system relevant to the desired reprogramming task.
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spelling doaj.art-862ed6c86f7e425fa9ed47db9210aa5e2022-12-22T02:38:26ZengNature Portfolionpj Systems Biology and Applications2056-71892022-06-018111510.1038/s41540-022-00231-yNETISCE: a network-based tool for cell fate reprogrammingLauren Marazzi0Milan Shah1Shreedula Balakrishnan2Ananya Patil3Paola Vera-Licona4Center for Quantitative Medicine, University of Connecticut School of MedicineCenter for Quantitative Medicine, University of Connecticut School of MedicineCenter for Quantitative Medicine, University of Connecticut School of MedicineCenter for Quantitative Medicine, University of Connecticut School of MedicineCenter for Quantitative Medicine, University of Connecticut School of MedicineAbstract The search for effective therapeutic targets in fields like regenerative medicine and cancer research has generated interest in cell fate reprogramming. This cellular reprogramming paradigm can drive cells to a desired target state from any initial state. However, methods for identifying reprogramming targets remain limited for biological systems that lack large sets of experimental data or a dynamical characterization. We present NETISCE, a novel computational tool for identifying cell fate reprogramming targets in static networks. In combination with machine learning algorithms, NETISCE estimates the attractor landscape and predicts reprogramming targets using signal flow analysis and feedback vertex set control, respectively. Through validations in studies of cell fate reprogramming from developmental, stem cell, and cancer biology, we show that NETISCE can predict previously identified cell fate reprogramming targets and identify potentially novel combinations of targets. NETISCE extends cell fate reprogramming studies to larger-scale biological networks without the need for full model parameterization and can be implemented by experimental and computational biologists to identify parts of a biological system relevant to the desired reprogramming task.https://doi.org/10.1038/s41540-022-00231-y
spellingShingle Lauren Marazzi
Milan Shah
Shreedula Balakrishnan
Ananya Patil
Paola Vera-Licona
NETISCE: a network-based tool for cell fate reprogramming
npj Systems Biology and Applications
title NETISCE: a network-based tool for cell fate reprogramming
title_full NETISCE: a network-based tool for cell fate reprogramming
title_fullStr NETISCE: a network-based tool for cell fate reprogramming
title_full_unstemmed NETISCE: a network-based tool for cell fate reprogramming
title_short NETISCE: a network-based tool for cell fate reprogramming
title_sort netisce a network based tool for cell fate reprogramming
url https://doi.org/10.1038/s41540-022-00231-y
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