Researchers from the University of Chicago and Stanford University explore regulatory variation in human induced pluripotent stem cells (iPSC) and cells that undergone differentiation. Using RNA sequence-based expression clues, chromatin accessibility information gleaned from ATAC-seq, and array-based DNA methylation profiling, the team characterized iPSCs established from 58 Yoruba lymphoblastoid cell lines, along with 14 cardiomyocyte lines differentiated from that iPSC set. "While most cell type-specific regulatory quantitative trait loci lie in chromatin that is open only in the affected cell types, we found that 20 [percent] of cell type-specific regulatory QTLs are in shared open chromatin," the authors note, prompting them to take a closer look at common SNP contributions to chromatin accessibility in different cell types.
Stanford University's Michael Snyder leads a team considering transcriptome complexity with droplet-based isoform sequencing. The low-input approach — known as sparse isoform sequencing, or spISO-seq — involves tiling linked reads that have been generated with the 10X Genomics GemCode platform, according to the team. It applied spISO-seq to DNA from a human brain sample, comparing it to other sequencing approaches such as synthetic long read sequencing (SLR-RNA-seq). The analysis highlighted splicing coordination across long distances in highly expressed protein-coding genes, which dipped in non-coding sequences. "Our results provide a more comprehensive understanding of the human transcriptome," the team writes, "and a general, cost effective method to analyze it."
South Korean researchers introduce a "simultaneous isolation and parallel sequencing of genomic DNA and total RNA" (SIDR) from individual cells. By combining nuclear lamina preserving hypotonic lysis with antibody-linked magnetic microbead capture, the researchers report, the SIDR method plucks genomic DNA and total RNA from the same cell for further analysis. Their results suggest that this strategy efficiently isolates genetic material that can be sequenced to identify everything from single nucleotide changes to copy number shifts. "We have demonstrated the ability of SIDR to physically separate genomic DNA and total RNA from the same single cell without a discernible loss of either DNA or RNA or cross-contamination of nucleic acids," the authors say.