In PLoS Computational Biology this week, Marc Marti-Renom at Spain's Centro de Investigación Príncipe Felipe and MIT's Leonid Mirny discuss "bridging the resolution gap for structural determination of genomes" using computational approaches that expand upon existing knowledge of chromatin folding principles. In its paper, the duo describes computational approaches "for integrating experimental data with polymer physics," which they say could help researchers chip away at 3D genomic architecture.
Elsewhere in the same journal, the University of Wisconsin, Madison's Dongjun Chung et al. show that, with ChIP-seq, the "incorporation of multi-reads significantly increases sequencing depths, leads to detection of novel peaks that are not otherwise identifiable with uni-reads, and improves detection of peaks in mappable regions." Using ChIP-seq data sets for human STAT1 and mouse GATA1, Chung and his colleagues applied their approach for "allocating multi-reads as fractional counts using a weighted alignment scheme," finding that, "overall, peaks from multi-read analysis have similar characteristics to peaks that are identified by uni-reads except that the majority of them reside in segmental duplications."
Over in PLoS One, investigators at Cedars-Sinai Medical Center in Los Angeles and elsewhere show that "early in vitro differentiation of mouse definitive endoderm is not correlated with progressive maturation of nuclear DNA methylation patterns." Using 3D fluorescence imaging and "comprehensive topological cell-by-cell analyses with a novel image-cytometrical approach," the team sought to identify in situ global nuclear DNA methylation patterns during early endodermal differentiation of mouse embryonic stem cells. Notably, the team found that "the progression of global DNA methylation is not correlated with the standard transcription factors associated with endodermal development," it writes, adding that further research will be needed "to determine whether the progression of global methylation could represent a useful signature of cellular differentiation."
And in PLoS Biology this week, an international team led by researchers at Germany's Max Planck Institute for Molecular Biomedicine reports its "generation of healthy mice from gene-corrected disease-specific induced pluripotent stem cells." More specifically, using the murine model of tyrosinemia type 1, which is marked by fumarylacetoacetate hydrolase deficiency, the team "transduced FAH [fumarylacetoacetate hydrolase] cDNA into the FAH−/−-iPS cells using a third-generation lentiviral vector to generate gene-corrected iPS cells." In discussing the results of its experiment, the team says that the "genetic manipulation of iPS cells in combination with tetraploid embryo aggregation provides a practical and rapid approach to evaluate the efficacy of gene correction of human diseases in mouse models."