Hirst, D. | bioRxiv Science

bioRxiv2024

MOTL: enhancing multi-omics matrix factorization with transfer learning

Joint matrix factorization is popular for extracting lower dimensional representations of multi-omics data but loses effectiveness with limited samples. Addressing this limitation, we introduce MOTL (Multi-Omics Transfer Learning), a framework that enhances MOFA (Multi-Omics Factor Analysis) by inferring latent factors for small multi-omics target datasets with respect to those inferred from a large heterogeneous learning dataset. We evaluated MOTL by designing simulated and real data protocols and demonstrated that MOTL improves the factorization of limited-sample multi-omics datasets when compared to factorization without transfer learning. When applied to actual glioblastoma samples, MOTL enhanced delineation of cancer status and subtype.

bioinformatics↗

bioRxiv2021

SMCHD1 variants may induce variegated expression in Facio Scapulo Humeral Dystophy and Bosma Arhinia and microphtalmia syndrome

An expanding number of genetic syndromes are linked to mutations in genes encoding factors that guide chromatin organization. Recently, distinct genetic syndromes have been linked to mutations in the SMCHD1 gene. However, the function of this non-canonical SMC protein remains partly defined in Human tissues. To address this question, we determined its epi-signature in type 2 Facio Scapulo Humeral Dystrophy (FSHD2) and Bosma Arhinia and Microphtalmia Syndrome (BAMS) linked to heterozygous mutations in this gene. By combining RNA-Seq, DNA methylation profiling and ChIP-Seq, we showed that SMCHD1 regulates repressed chromatin but also cis-regulatory elements and enhancers. Our results emphasize dual functions for SMCHD1, in chromatin compaction, chromatin insulation and gene regulation with variable outcomes and targets depending on tissues. We propose that altered DNA methylation and long-range chromatin organization at a number of loci required for development and tissue differentiation, trigger variegated gene expression in rare genetic diseases linked to heterozygous SMCHD1 mutations.

genetics↗