Submegabase-size topologically associating domains (TAD) have been observed in high-throughput chromatin interaction data (Hi-C). However, accurate detection of TADs depends on ultra-deep sequencing and sophisticated normalization procedures. Here we propose a fast and normalization-free method to decode the domains of chromosomes (deDoc) that utilizes structural information theory. By treating Hi-C contact matrix as a representation of a graph, deDoc partitions the graph into segments with minimal structural entropy. We show that structural entropy can also be used to determine the proper bin size of the Hi-C data. By applying deDoc to pooled Hi-C data from 10 single cells, we detect megabase-size TAD-like domains. This result implies that the modular structure of the genome spatial organization may be fundamental to even a small cohort of single cells. Our algorithms may facilitate systematic investigations of chromosomal domains on a larger scale than hitherto have been possible.

Background: Study on long non-coding RNAs (lncRNAs) has been promoted by high-throughput RNA sequencing (RNA-Seq). However, it is still not trivial to identify lncRNAs from the RNA-Seq data and it remains a challenge to uncover their functions.Results: We present a computational pipeline for detecting novel lncRNAs from the RNA-Seq data. First, the genome-guided transcriptome reconstruction is used to generate initially assembled transcripts. The possible partial transcripts and artefacts are filtered according to the quantified expression level. After that, novel lncRNAs are detected by further filtering known transcripts and those with high protein coding potential, using a newly developed program called lncRScan. We applied our pipeline to a mouseKlf1knockout dataset, and discussed the plausible functions of the novel lncRNAs we detected by differential expression analysis. We identified 308 novel lncRNA candidates, which have shorter transcript length, fewer exons, shorter putative open reading frame, compared with known protein-coding transcripts. Of the lncRNAs, 52 large intergenic ncRNAs (lincRNAs) show lower expression level than the protein-coding ones and 13 lncRNAs represent significant differential expression between the wild-type andKlf1knockout conditions.Conclusions: Our method can predict a set of novel lncRNAs from the RNA-Seq data. Some of the lncRNAs are showed differentially expressed between the wild-type andKlf1knockout strains, suggested that those novel lncRNAs can be given high priority in further functional studies.

Background: The three-dimensional (3D) architecture of the genome has a highly ordered and hierarchical nature, which influences the regulation of essential nuclear processes at the basis of gene expression, such as gene transcription. While the hierarchical organization of heterochromatin and euchromatin can underlie differences in gene expression that determine evolutionary differences among species, the way 3D genome architecture is affected by evolutionary forces within major lineages remains unclear. Here, we report a comprehensive comparison of 3D genomes, using high resolution Hi-C data in fibroblast cells of fish, chickens, and 10 mammalian species.Results: This analysis shows a correlation between genome size and chromosome length that affects chromosome territory (CT) organization in the upper hierarchy of genome architecture, whereas lower hierarchical features, including local transcriptional availability of DNA, are selected through the evolution of vertebrates. Furthermore, conservation of topologically associating domains (TADs) appears strongly associated with the modularity of expression profiles across species. Additionally, LINE and SINE transposable elements likely contribute to heterochromatin and euchromatin organization, respectively, during the evolution of genome architecture.Conclusions: Our analysis uncovers organizational features that appear to determine the conservation and transcriptional regulation of functional genes across species. These findings can guide ongoing investigations of genome evolution by extending our understanding of the mechanisms shaping genome architecture.

Topologically associating domains (TAD) are a key structure of the 3D mammalian genomes. However, the prevalence and dynamics of TAD-like domains in single cells remain elusive. Here we develop a new algorithm, named deTOKI, to decode TAD-like domains with single-cell Hi-C data. By non-negative matrix factorization, deTOKI seeks regions that insulate the genome into blocks with minimal chance of clustering. deTOKI outperforms competing tools and reliably identifies TAD-like domains in single cells. Finally, we find that TAD-like domains are not only prevalent, but also subject to tight regulation in single cells.

Translational selection is a ubiquitous and significant mechanism to regulate protein expression in prokaryotes and unicellular eukaryotes. Recent evidence has shown that translational selection is weakly operative in highly expressed genes in human and other vertebrates. However, it remains unclear whether translational selection acts differentially on human genes depending on their expression patterns.

Background: Pigs are important animals for agricultural and biomedical research, and improvement is needed for use of the assisted reproductive technologies. Determining underlying mechanisms of epigenetic reprogramming in the early stage of preimplantation embryos derived from in vitro fertilization (IVF), parthenogenesis, and androgenesis will not only contribute to assisted reproductive technologies of pigs but also will shed light into early human development. However, the reprogramming of three-dimensional architecture of chromatin in this process in pigs is poorly understood. Results: We generate three-dimensional chromatin profiles for pig somatic cells, IVF, parthenogenesis, and androgenesis preimplantation embryos. We find that the chromosomes in the pig preimplantation embryos are enriched for superdomains, which are more rare in mice. However, p(s) curves, compartments, and topologically associated domains (TADs) are largely conserved in somatic cells and are gradually established during preimplantation embryogenesis in both mammals. In the uniparental pig embryos, the establishment of chromatin architecture is highly asynchronized at all levels from IVF embryos, and a remarkably strong decompartmentalization is observed during zygotic genome activation (ZGA). Finally, chromosomes originating from oocytes always establish TADs faster than chromosomes originating from sperm, both before and during ZGA. Conclusions: Our data highlight a potential unique 3D chromatin pattern of enriched superdomains in pig preimplantation embryos, an unusual decompartmentalization process during ZGA in the uniparental embryos, and an asynchronized TAD reprogramming between maternal and paternal genomes, implying a severe dysregulation of ZGA in the uniparental embryos in pigs.