Logistic PCA explains differences between genome-scale metabolic models in terms of metabolic pathways

Author(s)
Leopold Zehetner, Diana Széliová, Barbara Kraus, Juan A. Hernandez Bort, Jürgen Zanghellini
Abstract

Genome-scale metabolic models (GSMMs) offer a holistic view of biochemical reaction networks, enabling in-depth analyses of metabolism across species and tissues in multiple conditions. However, comparing GSMMs Against each other poses challenges as current dimensionality reduction algorithms or clustering methods lack mechanistic interpretability, and often rely on subjective assumptions. Here, we propose a new approach utilizing logisitic principal component analysis (LPCA) that efficiently clusters GSMMs while singling out mechanistic differences in terms of reactions and pathways that drive the categorization. We applied LPCA to multiple diverse datasets, including GSMMs of 222 Escherichia-strains, 343 budding yeasts (Saccharomycotina), 80 human tissues, and 2943 Firmicutes strains. Our findings demonstrate LPCA’s effectiveness in preserving microbial phylogenetic relationships and discerning human tissue-specific metabolic profiles, exhibiting comparable performance to traditional methods like t-distributed stochastic neighborhood embedding (t-SNE) and Jaccard coefficients. Moreover, the subsystems and associated reactions identified by LPCA align with existing knowledge, underscoring its reliability in dissecting GSMMs and uncovering the underlying drivers of separation.

Organisation(s)
Department of Analytical Chemistry
External organisation(s)
Baxalta Innovations GmbH, Vienna Doctoral School in Chemistry (DoSChem)
Journal
PLoS Computational Biology
Volume
20
ISSN
1553-734X
DOI
https://doi.org/10.1371/journal.pcbi.1012236
Publication date
06-2024
Peer reviewed
Yes
Austrian Fields of Science 2012
104027 Computational chemistry, 106005 Bioinformatics
ASJC Scopus subject areas
Ecology, Evolution, Behavior and Systematics, Modelling and Simulation, Ecology, Molecular Biology, Genetics, Cellular and Molecular Neuroscience, Computational Theory and Mathematics
Portal url
https://ucrisportal.univie.ac.at/en/publications/logistic-pca-explains-differences-between-genomescale-metabolic-models-in-terms-of-metabolic-pathways(6d991282-7dd2-4618-82ee-66c4a2f08fd1).html