Learning a genome-wide score of human-mouse conservation at the functional genomics level

Abstract

Identifying genomic regions with functional genomic properties that are conserved between human and mouse is an important challenge in the context of mouse model studies. To address this, we take a novel approach and learn a score of evidence of conservation at the functional genomics level by integrating large-scale information in a compendium of epigenomic, transcription factor binding, and transcriptomic data from human and mouse. The computational method we developed to do this, Learning Evidence of Conservation from Integrated Functional genomic annotations (LECIF), trains a neural network, which is then used to generate a genome-wide score in human and mouse. The resulting LECIF score highlights human and mouse regions with shared functional genomic properties and captures correspondence of biologically similar human and mouse annotations even though it was not explicitly given such information. LECIF will be a resource for mouse model studies.

A mammalian methylation array for profiling methylation levels at conserved sequences

“…We characterize the CpGs located on the mammalian methylation array regarding (a) CpG island status in different phylogenetic orders, (b) chromatin state analysis, and (c) LECIF score of evidence of human-mouse conservation at the functional genomics level 26 . (a) The boxplots report the median number (and interquartile range) of CpGs that map to CpG islands in mammalian species of a given phylogenetic order (x-axis).…”

“…exon, promoter, 5 prime untranslated region) and CpG island status (Supplementary Data). For human and mice we provide chromatin state annotations (Ernst and Kellis, 2012;Gorkin et al, 2020;Roadmap Epigenomics Consortium et al, 2015;Vu and Ernst, 2020) and the LECIF score on evidence of conservation at the functional genomics level between human and mouse (Kwon and Ernst, 2020).…”

“…We also provide in the annotation files of the array ChromHMM chromatin state annotations for mouse from (Gorkin et al, 2020). The human-mouse LECIF score was from (Kwon and Ernst, 2020).…”

“…While the mammalian methylation array was specifically designed to profile CpGs in highly conserved stretches of DNA based on sequence conservation, we assessed whether there was also evidence of conservation at the functional genomics level using human-mouse LECIF scores (Kwon and Ernst, 2020). The human-mouse LECIF quantifies evidence of conservation between human and mouse at the functional genomics level using chromatin state and other functional genomic annotations.…”

AdaLiftOver: High-resolution identification of orthologous regulatory elements with adaptive liftOver

“…Minnoye et al ., 2020 discovered examples of orthologous enhancers that sequence-based methods failed to identify. Beyond sequence conservation, functional genomic annotations are important complementary information to determine orthology (Kwon and Ernst, 2021). Many studies have revealed the evolutionary landscape of genomes and epigenomes by comparing matched datasets across species (Villar et al , 2015; Gjoneska et al ., 2015; Vierstra et al, 2014; Cheng et al ., 2014; Brawand et al ., 2011; Odom et al ., 2007).…”