An orchestra of machine learning methods reveals landmarks in single-cell data exemplified with aging fibroblasts

by Lauritz Rasbach, Aylin Caliskan, Fatemeh Saderi, Thomas Dandekar, Tim Breitenbach In this work, a Python framework for characteristic feature extraction is developed and applied to gene expression data of human fibroblasts. Unlabeled feature selection objectively determines groups and minimal gene sets separating groups. ML explainability methods transform the features correlat ing with phenotypic differences into causal reasoning, supported by further pipeline and visualization tools, allowing user knowledge to boost causal reasoning. The purpose of the framework is to identify characteristic features that are causally related to phenotypic differences of single cells. Th e pipeline consists of several data science methods enriched with purposeful visualization of the intermediate results in order to check them systematically and infuse the domain knowledge about the investigated process. A specific focus is to extract a small but meaningful set of genes to facilitat e causal reasoning for the phenotypic differences. One application could be drug target identification. For this purpose, the framework follows different steps: feature reduction (PFA), low dimensional embedding (UMAP), clustering ((H)DBSCAN), feature correlation (chi-square, mutual information), ML validation and explainability (SHAP, tree explainer). The pipeline is validated by identifying and correctly separating signature genes associated with aging in fibroblasts from single-cell gene expression measur...
Source: PLoS One - Category: Biomedical Science Authors: Source Type: research