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This Week in Nucleic Acids Research: Jan 20, 2016

Chinese researchers describe genome-wide methylation patterns they detected in a dozen strains from the Mycobacterium tuberculosis complex (MTBC) — including six clinical isolates of M. tuberculosis — with the help of de novo genome assemblies produced by single-molecule real-time sequencing. Using both sequence and methylation cues from PacBio reads, the team uncovered a handful of key motifs in the methylome, along with new insights into methyltransferase enzyme activity across the genome. "[W]e were able to discover the 'precision methylome' of the MTBC strains," the study's authors write, "which enabled an intricate analysis of [methyltransferase] activity on the scale of the whole-genome."

A team from Germany and Spain brought together nearly 1,750 new and existing omics datasets to delve into post-transcriptional regulation and proteome patterns in genome-reduced version of the Mycoplasma pneumoniae microbe. By combining these various sources of information, the researchers found that features such as non-coding RNAs, protein phosphorylation levels, and other amino acid modifications can provide more accurate estimates of protein abundance than those provided using messenger RNA alone. The results also highlighted the extent to which genome reduction affects not only proteome homeostasis, but also more general genetic patterns in the bug. 

Finally, investigators at the University of North Carolina-Chapel Hill and Sage Bionetworks present a mathematical model for teasing apart alternative splicing patterns in populations of individual cells assessed by single-cell RNA sequencing. The three-phase statistical approach, known as SingleSplice, is intended to uncover transcript isoforms through searches for biological variability at levels beyond technical noise — an approach that does not rely on information regarding full-length transcript expression. The team demonstrated the veracity of the approach using spike-in isoform experiments and analyses of individual mouse embryonic stem cells, where the method uncovered alternative splicing variability related to genes involved in the cell cycle.