Repeated measures ASCA+ for analysis of longitudinal intervention studies with multivariate outcome data

PLoS Comput Biol. 2021 Nov 9;17(11):e1009585. doi: 10.1371/journal.pcbi.1009585. eCollection 2021 Nov.

Abstract

Longitudinal intervention studies with repeated measurements over time are an important type of experimental design in biomedical research. Due to the advent of "omics"-sciences (genomics, transcriptomics, proteomics, metabolomics), longitudinal studies generate increasingly multivariate outcome data. Analysis of such data must take both the longitudinal intervention structure and multivariate nature of the data into account. The ASCA+-framework combines general linear models with principal component analysis and can be used to separate and visualize the multivariate effect of different experimental factors. However, this methodology has not yet been developed for the more complex designs often found in longitudinal intervention studies, which may be unbalanced, involve randomized interventions, and have substantial missing data. Here we describe a new methodology, repeated measures ASCA+ (RM-ASCA+), and show how it can be used to model metabolic changes over time, and compare metabolic changes between groups, in both randomized and non-randomized intervention studies. Tools for both visualization and model validation are discussed. This approach can facilitate easier interpretation of data from longitudinal clinical trials with multivariate outcomes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Immunological / therapeutic use
  • Bariatric Surgery
  • Bevacizumab / therapeutic use
  • Breast Neoplasms / drug therapy*
  • Data Interpretation, Statistical
  • Female
  • Genomics
  • Humans
  • Longitudinal Studies
  • Metabolomics
  • Proteomics
  • Reproducibility of Results

Substances

  • Antineoplastic Agents, Immunological
  • Bevacizumab

Grants and funding

TSM received a grant from the Norwegian Research School in Bioinformatics, Biostatistics and Systems Biology (NORBIS, https://norbis.w.uib.no/), and GFG received a grant from the Norwegian Cancer Society (grant number 6834362, https://kreftforeningen.no/en/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.