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Multi-omic Signatures of Host Response Associated with Presence, Type, and Outcome of Enterococcal Bacteremia metabolomics data

ABSTRACT: Meatbolomics data from the manuscript Multi-omic Signatures of Host Response Associated with the Presence, Type, and Outcome of Enterococcal Bacteremia.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: David Gonzalez

PROVIDER: MSV000096729 | MassIVE | Tue Dec 24 21:05:00 GMT 2024

REPOSITORIES: MassIVE

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Project description:To better understand dynamic disease processes, integrated multi-omic methods are needed, yet comparing different types of omic data remains difficult. Integrative solutions benefit experimenters by eliminating potential biases that come with single omic analysis. We have developed the methods needed to explore whether a relationship exists between co-expression network models built from transcriptomic and proteomic data types, and whether this relationship can be used to improve the disease signature discovery process. A naïve, correlation based method is utilized for comparison. Using publicly available infectious disease time series data, we analyzed the related co-expression structure of the transcriptome and proteome in response to SARS-CoV infection in mice. Transcript and peptide expression data was filtered using quality scores and subset by taking the intersection on mapped Entrez IDs. Using this data set, independent co-expression networks were built. The networks were integrated by constructing a bipartite module graph based on module member overlap, module summary correlation, and correlation to phenotypes of interest. Compared to the module level results, the naïve approach is hindered by a lack of correlation across data types, less significant enrichment results, and little functional overlap across data types. Our module graph approach avoids these problems, resulting in an integrated omic signature of disease progression, which allows prioritization across data types for down-stream experiment planning. Integrated modules exhibited related functional enrichments and could suggest novel interactions in response to infection. These disease and platform-independent methods can be used to realize the full potential of multi-omic network signatures. The data (experiment SM001) are publically available through the NIAID Systems Virology (https://www.systemsvirology.org) and PNNL (http://omics.pnl.gov) web portals. Phenotype data is found in the supplementary information. The ProCoNA package is available as part of Bioconductor 2.13.

Project description:Background: Primary knee osteoarthritis (KOA) is a heterogeneous disease with clinical and molecular contributors. Biofluids contain microRNAs and metabolites that can be measured by omic technologies. Deep learning captures complex non-linear associations within multimodal data but, to date, has not been used for multi-omic-based endotyping of KOA patients. We developed a novel multimodal deep learning framework for clustering of multi-omic data from three subject-matched biofluids to identify distinct KOA endotypes and classify one-year post-total knee arthroplasty (TKA) pain/function responses. Materials and Methods: In 414 KOA patients, subject-matched plasma, synovial fluid and urine were analyzed by microRNA sequencing or metabolomics. Integrating 4 high-dimensional datasets comprising metabolites from plasma (n=151 features), along with microRNAs from plasma (n=421), synovial fluid (n=930), or urine (n=1225), a multimodal deep learning variational autoencoder architecture with K-means clustering was employed. Features influencing cluster assignment were identified and pathway analyses conducted. An integrative machine learning framework combining 4 molecular domains and a clinical domain was then used to classify WOMAC pain/function responses post-TKA within each cluster. Findings: Multimodal deep learning-based clustering of subjects across 4 domains yielded 3 distinct patient clusters. Feature signatures comprising microRNAs and metabolites across biofluids included 30, 16, and 24 features associated with Clusters 1-3, respectively. Pathway analyses revealed distinct pathways associated with each cluster. Integration of 4 multi-omic domains along with clinical data improved response classification performance, with Cluster 3 achieving AUC=0·879 for subject pain response classification and Cluster 2 reaching AUC=0·808 for subject function response, surpassing individual domain classifications by 12% and 15% respectively. Interpretation: We have developed a deep learning-based multimodal clustering model capable of integrating complex multi-fluid, multi-omic data to assist in KOA patient endotyping and test outcome response to TKA surgery.

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Multi-omic Signatures of Host Response Associated with Presence, Type, and Outcome of Enterococcal Bacteremia metabolomics data

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