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In Nucleic acids research ; h5-index 217.0

We attempt to address a key question in the joint analysis of transcriptomic data: can we correlate the patterns we observe in transcriptomic datasets to known interactions and pathway knowledge to broaden our understanding of disease pathophysiology? We present a systematic approach that sheds light on the patterns observed in hundreds of transcriptomic datasets from over sixty indications by using pathways and molecular interactions as a template. Our analysis employs transcriptomic datasets to construct dozens of disease specific co-expression networks, alongside a human protein-protein interactome network. Leveraging the interoperability between these two network templates, we explore patterns both common and particular to these diseases on three different levels. Firstly, at the node-level, we identify most and least common proteins across diseases and evaluate their consistency against the interactome as a proxy for their prevalence in the scientific literature. Secondly, we overlay both network templates to analyze common correlations and interactions across diseases at the edge-level. Thirdly, we explore the similarity between patterns observed at the disease-level and pathway knowledge to identify signatures associated with specific diseases and indication areas. Finally, we present a case scenario in schizophrenia, where we show how our approach can be used to investigate disease pathophysiology.

Figueiredo Rebeca Queiroz, Raschka Tamara, Kodamullil Alpha Tom, Hofmann-Apitius Martin, Mubeen Sarah, Domingo-Fernández Daniel

2021-Jul-01