Integrated transcriptomic and single cell analysis combined with artificial neural network identifies a robust gene signature for early discrimination of MASL and MASH

BackgroundMetabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disease, ranging from simple steatosis (MASL) to metabolic dysfunction-associated steatohepatitis (MASH). However, reliable noninvasive strategies for accurately distinguishing MASL from MASH at an early stage remain limited.

We therefore aimed to develop a robust molecular model to improve early identification of disease progression and subtype discrimination.MethodsFive datasets from the Gene Expression Omnibus were integrated as a training cohort comprising 149 MASL and 158 MASH samples, while another dataset GSE135251 served as validation cohort including 51 MASL and 155 MASH samples. Differential expression analysis and weighted gene co expression network analysis were conducted to identify gene modules.

Overlapping genes were subjected to protein interaction network construction and topological ranking. Least absolute shrinkage and selection operator regression, support vector machine recursive feature elimination, and random forest algorithms were jointly applied to derive robust diagnostic candidates.

An artificial neural network classifier was established based on the final gene set and evaluated in both cohorts. Immune cell composition was estimated using CIBERSORT.