Search for: All records

Genome-wide nucleosome profiles are predominantly characterized using MNase-seq, which involves extensive MNase digestion and size selection to enrich for mononucleosome-sized fragments. Most available MNase-seq analysis packages assume that nucleosomes uniformly protect 147 bp DNA fragments. However, some nucleosomes with atypical histone or chemical compositions protect shorter lengths of DNA. The rigid assumptions imposed by current nucleosome analysis packages potentially prevent investigators from understanding the regulatory roles played by atypical nucleosomes. To enable the characterization of different nucleosome types from MNase-seq data, we introduce the size-based expectation maximization (SEM) nucleosome-calling package. SEM employs a hierarchical Gaussian mixture model to estimate nucleosome positions and subtypes. Nucleosome subtypes are automatically identified based on the distribution of protected DNA fragments. Benchmark analysis indicates that SEM is on par with existing packages in terms of standard nucleosome-calling accuracy metrics, while uniquely providing the ability to characterize nucleosome subtype identities. Applying SEM to a low-dose MNase-H2B-ChIP-seq data set from mouse embryonic stem cells, we identified three nucleosome types: short-fragment nucleosomes, canonical nucleosomes, and di-nucleosomes. Short-fragment nucleosomes can be divided further into two subtypes based on their chromatin accessibility. Short-fragment nucleosomes in accessible regions exhibit high MNase sensitivity and are enriched at transcription start sites (TSSs) and CTCF peaks, similar to previously reported “fragile nucleosomes.” These SEM-defined accessible short-fragment nucleosomes are found not just in promoters but also in distal regulatory regions. Additional analyses reveal their colocalization with the chromatin remodelers CHD6, CHD8, and EP400. In summary, SEM provides an effective platform for exploration of nonstandard nucleosome subtypes. 

Abstract Causal inference in complex systems has been largely promoted by the proposal of some advanced temporal causation models. However, temporal models have serious limitations when time series data are not available or present insignificant variations, which causes a common challenge for earth system science. Meanwhile, there are few spatial causation models for fully exploring the rich spatial cross-sectional data in Earth systems. The generalized embedding theorem proves that observations can be combined together to construct the state space of the dynamic system, and if two variables are from the same dynamic system, they are causally linked. Inspired by this, here we show a Geographical Convergent Cross Mapping (GCCM) model for spatial causal inference with spatial cross-sectional data-based cross-mapping prediction in reconstructed state space. Three typical cases, where clearly existing causations cannot be measured through temporal models, demonstrate that GCCM could detect weak-moderate causations when the correlation is not significant. When the coupling between two variables is significant and strong, GCCM is advantageous in identifying the primary causation direction and better revealing the bidirectional asymmetric causation, overcoming the mirroring effect.