eXplainable Artificial Intelligence (XAI) for the identification of biologically relevant gene expression patterns in longitudinal human studies, insights from obesity research

PLoS Comput Biol. 2020 Apr 10;16(4):e1007792. doi: 10.1371/journal.pcbi.1007792. eCollection 2020 Apr.

Abstract

Until date, several machine learning approaches have been proposed for the dynamic modeling of temporal omics data. Although they have yielded impressive results in terms of model accuracy and predictive ability, most of these applications are based on "Black-box" algorithms and more interpretable models have been claimed by the research community. The recent eXplainable Artificial Intelligence (XAI) revolution offers a solution for this issue, were rule-based approaches are highly suitable for explanatory purposes. The further integration of the data mining process along with functional-annotation and pathway analyses is an additional way towards more explanatory and biologically soundness models. In this paper, we present a novel rule-based XAI strategy (including pre-processing, knowledge-extraction and functional validation) for finding biologically relevant sequential patterns from longitudinal human gene expression data (GED). To illustrate the performance of our pipeline, we work on in vivo temporal GED collected within the course of a long-term dietary intervention in 57 subjects with obesity (GSE77962). As validation populations, we employ three independent datasets following the same experimental design. As a result, we validate primarily extracted gene patterns and prove the goodness of our strategy for the mining of biologically relevant gene-gene temporal relations. Our whole pipeline has been gathered under open-source software and could be easily extended to other human temporal GED applications.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Artificial Intelligence / trends
  • Computational Biology / methods*
  • Data Mining / methods*
  • Databases, Genetic
  • Gene Expression / genetics
  • Gene Expression Profiling / methods*
  • Humans
  • Longitudinal Studies
  • Machine Learning
  • Obesity / genetics
  • Software
  • Transcriptome / genetics

Grants and funding

This work was supported by the Mapfre Foundation (“Research grants by Ignacio H. de Larramendi 2017”) and by the Regional Government of Andalusia ("Plan Andaluz de investigación, desarrollo e innovación (2018), P18-RT-2248"). The authors also acknowledge the Institute of Health Carlos III for personal funding: Contratos i-PFIS: doctorados IIS-empresa en ciencias y tecnologías de la salud de la convocatoria 2017 de la Acción Estratégica en Salud 2013–2016, Project number: IFI17/00048. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.