A1 Refereed original research article in a scientific journal
Longitudinal pathway analysis using structural information with case studies in early type 1 diabetes
Authors: Jaakkola, Maria K.; Kukkonen-Macchi, Anu; Suomi, Tomi; Elo, Laura L.
Publisher: Springer Science and Business Media LLC
Publishing place: BERLIN
Publication year: 2025
Journal: Scientific Reports
Journal name in source: Scientific Reports
Journal acronym: SCI REP-UK
Article number: 15393
Volume: 15
Issue: 1
Number of pages: 11
ISSN: 2045-2322
eISSN: 2045-2322
DOI: https://doi.org/10.1038/s41598-025-98492-0
Web address : https://doi.org/10.1038/s41598-025-98492-0
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/498585933
Pathway analysis is a frequent step in studies involving gene or protein expression data, but most of the available pathway methods are designed for simple case versus control studies of two sample groups without further complexity. The few available methods allowing the pathway analysis of more complex study designs cannot use pathway structures or handle the situation where the variable of interest is not defined for all samples. Such scenarios are common in longitudinal studies with so long follow up time that healthy controls are required to identify the effect of normal aging apart from the effect of disease development, which is not defined for controls. To address the need, we introduce a new method for Pathway Analysis of Longitudinal data (PAL), which is suitable for complex study designs, such as longitudinal data. The main advantages of PAL are the use of pathway structures and the suitability of the approach for study settings beyond currently available tools. We demonstrate the performance of PAL with simulated data and three longitudinal datasets related to the early development of type 1 diabetes, which involve different study designs and only subtle biological signals, and include both transcriptomic and proteomic data. An R package implementing PAL is publicly available at https://github.com/elolab/PAL.
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Funding information in the publication:
Prof. Elo reports grants from the European Research Council ERC (677943), European Union’s Horizon 2020 research and innovation programme (955321), Academy of Finland (310561, 314443, 329278, 335434, 335611 and 341342), and Sigrid Juselius Foundation during the conduct of the study. Our research is also supported by Biocenter Finland and ELIXIR Finland.
