A Pathway-Level Information ExtractoR (PLIER) framework to gain mechanistic insights into obesity in Down syndrome – James C. Costello (University of Colorado Denver)

Down syndrome (DS), caused by the triplication of chromosome 21 (T21), is a prevalent genetic disorder with a higher incidence of obesity. It has been a challenge to differentiate T21-specific molecular dysregulation from general obesity-related processes. We introduce the omni-PLIER framework, combining the Pathway-Level Information ExtractoR (PLIER) with the omnigenic model, to uncover molecular mechanisms underlying obesity in DS. The PLIER framework aligns gene expression data with biological pathways, facilitating the identification of relevant molecular patterns. Using RNA sequencing data from the Human Trisome Project, omni-PLIER identified latent variables (LVs) significantly associated with T21 and body mass index (BMI). The omni-PLIER model allows us to dissect obesity-related processes in both DS and the general population.