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The human genome is marked by several singular and combinatorial histone modifications that shape the different states of chromatin and its three-dimensional organization. Genome-wide mapping of these marks as well as histone variants and open chromatin regions is commonly carried out via profiling DNA–protein binding or via chromatin accessibility methods. After the generation of epigenomic datasets in a cell type, statistical models can be used to annotate the noncoding regions of DNA and infer the combinatorial histone marks or chromatin states (CS). These methods involve partitioning the genome and labeling individual segments based on their CS patterns. Chromatin labels enable the systematic discovery of genomic function and activity and can label the gene body, promoters or enhancers without using other genomic maps. CSs are dynamic and change under different cell conditions, such as in normal, preneoplastic or tumor cells. This review aims to explore the available computational tools that have been developed to capture CS alterations under two or more cellular conditions. [ABSTRACT FROM AUTHOR]

To enhance reproducibility in scientific research, more and more datasets are becoming publicly available so that researchers can perform secondary analyses to investigate questions the original scientists had not posited. This increases the return on investment for the NIH and other funding bodies. These datasets, however, are not perfect, and a better understanding of the assumptions that shaped them is required. The 2020 Junior Research Parasite Award recognized our work that showed that the signal-to-noise ratio in a particular dataset had not been investigated, leading to an erroneous conclusion in the original research. In this commentary, I share the process that led to the identification of the problem and hopefully provide useful lessons for other research parasites. [ABSTRACT FROM AUTHOR]

Motivation: Batch effects are one of the major source of technical variations that affect the measurements in high-throughput studies such as RNA sequencing. It has been well established that batch effects can be caused by different experimental platforms, laboratory conditions, different sources of samples and personnel differences. These differences can confound the outcomes of interest and lead to spurious results. A critical input for batch correction algorithms is the knowledge of batch factors, which in many cases are unknown or inaccurate. Hence, the primary motivation of our paper is to detect hidden batch factors that can be used in standard techniques to accurately capture the relationship between gene expression and other modeled variables of interest. Results: We introduce a new algorithm based on data-adaptive shrinkage and semi-Non-negative Matrix Factorization for the detection of unknown batch effects. We test our algorithm on three different datasets: (i) Sequencing Quality Control, (ii) Topotecan RNA-Seq and (iii) Single-cell RNA sequencing (scRNA-Seq) on Glioblastoma Multiforme. We have demonstrated a superior performance in identifying hidden batch effects as compared to existing algorithms for batch detection in all three datasets. In the Topotecan study, we were able to identify a new batch factor that has been missed by the original study, leading to under-representation of differentially expressed genes. For scRNA-Seq, we demonstrated the power of our method in detecting subtle batch effects. [ABSTRACT FROM AUTHOR]