PathFinder: a novel graph transformer model to infer multi-cell intra- and inter-cellular signaling pathways and communications.

Alzheimer’s disease cell cell signaling communications graph neural network microenvironment signaling pathways

Journal

Frontiers in cellular neuroscience
ISSN: 1662-5102
Titre abrégé: Front Cell Neurosci
Pays: Switzerland
ID NLM: 101477935

Informations de publication

Date de publication:
2024
Historique:
received: 11 01 2024
accepted: 30 04 2024
medline: 7 6 2024
pubmed: 7 6 2024
entrez: 7 6 2024
Statut: epublish

Résumé

Recently, large-scale scRNA-seq datasets have been generated to understand the complex signaling mechanisms within the microenvironment of Alzheimer's Disease (AD), which are critical for identifying novel therapeutic targets and precision medicine. However, the background signaling networks are highly complex and interactive. It remains challenging to infer the core intra- and inter-multi-cell signaling communication networks using scRNA-seq data. In this study, we introduced a novel graph transformer model, PathFinder, to infer multi-cell intra- and inter-cellular signaling pathways and communications among multi-cell types. Compared with existing models, the novel and unique design of PathFinder is based on the divide-and-conquer strategy. This model divides complex signaling networks into signaling paths, which are then scored and ranked using a novel graph transformer architecture to infer intra- and inter-cell signaling communications. We evaluated the performance of PathFinder using two scRNA-seq data cohorts. The first cohort is an APOE4 genotype-specific AD, and the second is a human cirrhosis cohort. The evaluation confirms the promising potential of using PathFinder as a general signaling network inference model.

Identifiants

pubmed: 38846640
doi: 10.3389/fncel.2024.1369242
pmc: PMC11155453
doi:

Types de publication

Journal Article

Langues

eng

Pagination

1369242

Informations de copyright

Copyright © 2024 Feng, Song, Province, Li, Payne, Chen and Li.

Déclaration de conflit d'intérêts

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Auteurs

Jiarui Feng (J)

Institute for Informatics (I2), Washington University School of Medicine, Washington University in St. Louis, St. Louis, MO, United States.
Department of Computer Science and Engineering, Washington University in St. Louis, St. Louis, MO, United States.

Haoran Song (H)

Institute for Informatics (I2), Washington University School of Medicine, Washington University in St. Louis, St. Louis, MO, United States.
Department of Computer Science and Engineering, Washington University in St. Louis, St. Louis, MO, United States.

Michael Province (M)

Division of Statistical Genomics, Department of Genetics, Washington University in St. Louis, St. Louis, MO, United States.

Guangfu Li (G)

Department of Surgery, University of Missouri-Columbia, Columbia, MO, United States.
Department of Molecular Microbiology and Immunology, University of Missouri-Columbia, Columbia, MO, United States.
NextGen Precision Health Institute, University of Missouri-Columbia, Columbia, MO, United States.

Philip R O Payne (PRO)

Institute for Informatics (I2), Washington University School of Medicine, Washington University in St. Louis, St. Louis, MO, United States.

Yixin Chen (Y)

Department of Computer Science and Engineering, Washington University in St. Louis, St. Louis, MO, United States.

Fuhai Li (F)

Institute for Informatics (I2), Washington University School of Medicine, Washington University in St. Louis, St. Louis, MO, United States.
Department of Pediatrics, Washington University School of Medicine, Washington University in St. Louis, St. Louis, MO, United States.

Classifications MeSH