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bioRxiv2019

Integrated multi-omics analysis to study the effects of simulated weightlessness on rhesus macaques (Macaca mulatta)

Safety and health of astronauts in space is one of the most important aspects of space exploration, however, the genomic research about how a weightless space can affect astronauts health was limited. In this study, we sequenced 25 transcriptomic, 42 metabolomic and 35 metagenomic data of 15 rhesus macaques (Macaca mulatta) spanning seven simulated weightlessness experiment stages. We identified 84 genes, 1911 features and 55 genera which are significantly changed in blood and muscle, hippocampal region, dorsomedial prefrontal cortex as well as fecal, respectively. Furthermore, performing the integrated analysis of three omics data, we found several pathways which were related to regulation of immune system process, glucose uptake, reaction to threatens, neurotoxic and bone or joints damage, such as tyrosine metabolism and tryptophan metabolism. Our results provided an initial attempt of "multi-omics" approaches which combined transcriptomics, metabolomics and metagenomics to illustrate some molecular clues for simulated weightlessness effect on the rhesus macaques and potential sight of microgravitys effect on astronauts health.

immunology↗

bioRxiv2018

Mate-pair Library Construction with Controlled Polymerization Enables Comprehensive Structural Rearrangement Detection

The diversity of disease presentations warrants one single assay for detection and delineation of various genomic disorders. Herein, we describe a gel-free and biotin-capture-free mate-pair method through coupling Controlled Polymerizations by Adapter-Ligation (CP-AL). We first demonstrated the feasibility and ease-of-use in monitoring DNA nick-translation and primer extension by limiting the nucleotide input. By coupling these two controlled polymerizations by a reported non-conventional adapter ligation reaction 3 branch ligation, we evidenced that CP-AL significantly increased DNA-circularization efficiency (by 4-fold) and was applicable for different sequencing methods but at a faction of current cost. Its advantages were further demonstrated by fully elimination of small-insert-contaminated (by 39.3-fold) with a ~50% increment of physical coverage, and producing uniform genome/exome coverage and the lowest chimeric rate. It achieved single-nucleotide variants detection with sensitivity and specificity up to 97.3 and 99.7%, respectively, compared with data from small-insert libraries. In addition, this method can provide a comprehensive delineation of structural rearrangements, evidenced by a potential diagnosis in a patient with oligo-atheno-terato-spermia. Moreover, it enables accurate mutation identification by integration of genomic variants from different aberration types. Overall, it provides a potential single-integrated solution for detecting various genomic variants, facilitating a genetic diagnosis in human diseases.

genomics↗