Biology subjects

Xi, R.

Publications and source records attributed to Xi, R..

3 recordsLinked to original sources

bioRxiv2018

Comprehensive analysis of chromothripsis in 2,658 human cancers using whole-genome sequencing

Chromothripsis is a newly discovered mutational phenomenon involving massive, clustered genomic rearrangements that occurs in cancer and other diseases. Recent studies in cancer suggest that chromothripsis may be far more common than initially inferred from low resolution DNA copy number data. Here, we analyze the patterns of chromothripsis across 2,658 tumors spanning 39 cancer types using whole-genome sequencing data. We find that chromothripsis events are pervasive across cancers, with a frequency of >50% in several cancer types. Whereas canonical chromothripsis profiles display oscillations between two copy number states, a considerable fraction of the events involves multiple chromosomes as well as additional structural alterations. In addition to non-homologous end-joining, we detect signatures of replicative processes and templated insertions. Chromothripsis contributes to oncogene amplification as well as to inactivation of genes such as mismatch-repair related genes. These findings show that chromothripsis is a major process driving genome evolution in human cancer.

genomics↗

bioRxiv2017

Clustering enzymes using E.coli inner cell membrane as scaffold in metabolic pathway

Clustering enzymes in the same metabolism pathway is a natural strategy to enhance the productivity. Several systems have been designed to artificially cluster desired enzymes in the cell, such as synthetic protein scaffold and nucleic acid scaffold. However, these scaffolds require complicated construction process and have limited slots for target enzymes. Following this direction, we designed a scaffold system based on natural cell membrane. Target enzymes (FabZ, FabG, FabI and TesA in fatty acid synthesis II pathway) are anchored on the E.coli inner membrane, showing the enhanced metabolism flux without the requirement of the further artificial interactions to force the clustering. Furthermore, anchoring the enzymes on the membrane enhances the products exportation, which further increases the productivity. Together, the proposed system has potential applications in producing valuable biomaterials.

synthetic biology↗

bioRxiv2017

Genomic footprints of activated telomere maintenance mechanisms in cancer

Cancers require telomere maintenance mechanisms for unlimited replicative potential. We dissected whole-genome sequencing data of over 2,500 matched tumor-control samples from 36 different tumor types to characterize the genomic footprints of these mechanisms. While the telomere content of tumors with ATRX or DAXX mutations (ATRX/DAXXtrunc) was increased, tumors with TERT modifications showed a moderate decrease of telomere content. One quarter of all tumor samples contained somatic integrations of telomeric sequences into non-telomeric DNA. With 80% prevalence, ATRX/DAXXtrunc tumors display a 3-fold enrichment of telomere insertions. A systematic analysis of telomere composition identified aberrant telomere variant repeat (TVR) distribution as a genomic marker of ATRX/DAXXtrunc tumors. In this clinically relevant subgroup, singleton TTCGGG and TTTGGG TVRs (previously undescribed) were significantly enriched or depleted, respectively. Overall, our findings provide new insight into the recurrent genomic alterations that are associated with the establishment of different telomere maintenance mechanisms in cancer.

genomics↗