ModHMM: A Modular Supra-Bayesian Genome Segmentation Method

Abstract

Genome segmentation methods are powerful tools to obtain cell type or tissue-specific genome-wide annotations and are frequently used to discover regulatory elements. However, traditional segmentation methods show low predictive accuracy and their data-driven annotations have some undesirable properties. As an alternative, we developed ModHMM, a highly modular genome segmentation method. Inspired by the supra-Bayesian approach, it incorporates predictions from a set of classifiers. This allows to compute genome segmentations by utilizing state-of-the-art methodology. We demonstrate the method on EN-CODE data and show that it outperforms traditional segmentation methods not only in terms of predictive performance, but also in qualitative aspects. Therefore, ModHMM is a valuable alternative to study the epigenetic and regulatory landscape across and within cell types or tissues.

Quantifying the Tissue-Specific Regulatory Information within Enhancer DNA Sequences

“…We obtained data from eight tissues (heart, kidney, liver, limb, lung, forebrain, midbrain, hindbrain) of embryonic mouse at day 15.5 from the ENCODE project (Supplementary Tables 26 and 27). ModHMM [Benner and Vingron, 2020] was used to compute genome segmentations for each of the tissues. The segmentations provide, among others, the genomic coordinates of several types of regulatory elements within each tissue, such as active promoters and enhancers as well as primed regions.…”

“…ENCODE provides comparable epigenetic data across several tissues in the mouse embryo. We use ModHMM [Benner and Vingron, 2020] for computing genome segmentations based on ATAC-seq, RNA-seq, and ChIP-seq data for multiple histone modifications. ModHMM computes highly accurate annotations of active enhancers that are not tainted by promoter elements or inactive (e.g.…”

The ‘standard of civilization’ in international law: Intellectual perspectives from pre-war Japan

“…US President Theodore Roosevelt even advocated for a Japanese version of the Monroe Doctrine. 142 On 26 February 1895, Charles Denby, as American Minister to Peking, reported to the State Department that: 'Of the two Oriental nations [i.e., Japan and China] which were opened to Western civilization by foreign guns, one accepted the results, the other rejected them. Japan is now doing for China what the United States did for Japan.…”

“…117 Even sympathetic foreigners doubted whether any non-European people could establish a stable constitutional government of its own accord. 118 When Hirobumi led a delegation to Europe in 1883 to study its various national constitutions, the Prussian jurist Rudolf von Gneist advised them that a nation requires a certain level of cultural advancement to create a truly meaningful constitution rather than merely 'an elaborately embellished piece of paper'. Gneist indicated that 'in Japan's case the drafting of a constitution might very well be meaningless'.…”

“…US President Theodore Roosevelt even advocated for a Japanese version of the Monroe Doctrine. 142 On 26 February 1895, Charles Denby, as American Minister to Peking, reported to the State Department that:…”