zheng, h. | Search bioRxiv

bioRxiv2020

A Reference Feature based method for Quantification and Identification of LC-MS based untargeted metabolomics

Batch inconsistency is a major problem when applying LC-MS based untargeted metabolomics in real-time analysis situation such as clinical diagnosis or health monitoring. And inefficiency of collecting MS2 is a major problem for metabolite identification. Here, we developed a reference-feature based quantification and identification strategy (RFQI). In RFQI, samples are individually profiled using a pre-fixed reference feature table. Quantification results show that RFQI improves features overlap rate and reduce variance across batches significantly in real-time-analysis mode, and can find more than 4-fold numbers of features. Besides, RFQI collects MS2 from consecutive increasing samples for metabolite identification of pre-fixed features, thus it can effectively compensate for the poor efficiency of MS2 collection in data-dependent acquisition mode. In summary, RFQI can make full advantage of consecutive increasing samples in real-time analysis situation, both for quantification and identification.

bioinformatics↗

bioRxiv2019

The glycine locating at random coil of picornaviruses VP3 enhances viral pathogenicity by targeting p53 to promote apoptosis and autophagy

Picornaviruses, comprising important and widespread pathogens of humans and animals, have evolved to control apoptosis and autophagy for their replication and spread. However, the underlying mechanism of the association between apoptosis/autophage and viral pathogenicity remains unclear. In the present study, VP3 of picornaviruses was demonstrated to induce apoptosis and autophagy. Foot-and-mouth disease virus (FMDV), which served as a research model here, can strongly induce both apoptosis and autophagy in the skin lesions. By directly interacting with p53, FMDV-VP3 facilitates its phosphorylation and translocation, resulting in Bcl-2 family-mediated apoptosis and LC3-dependent autophagy. The single residue Gly129 of FMDV-VP3 plays a crucial role in apoptosis and autophagy induction and the interaction with p53. Consistently, the comparison of rescued FMDV with mutated Gly129 and parental virus showed that the Gly129 is indispensable for viral replication and pathogenicity. More importantly, the Gly129 locates at a bend region of random coil structure, the mutation of Gly to Ala remarkably shrunk the volume of viral cavity. Coincidentally, the Gly is conserved in the similarly location of other picornaviruses, including poliovirus (PV), enterovirus 71 (EV71), coxsackievirus (CV) and seneca valley virus (SVA). This study demonstrates that picornaviruses induce apoptosis and autophagy to facilitate its pathogenicity and the Gly is functional site, providing novel insights into picornavirus biology.

microbiology↗