Biology subjects

Wang, M.-R.

Publications and source records attributed to Wang, M.-R..

3 recordsLinked to original sources

bioRxiv2025

An integrated landscape of mRNA and protein isoforms

Alternative splicing and proteolytic processing expand the functional diversity of the human proteome by generating distinct protein isoforms from a single gene. However, the extent to which transcript isoforms give rise to distinct protein products remains unclear, in part due to technical limitations in proteomic workflows. Here, we combine full-length mRNA sequencing with SDS-PAGE-based protein fractionation and quantitative mass spectrometry to construct an integrated landscape of mRNA and protein isoforms in human RPE-1 cells. To overcome the inherent ambiguity of bottom-up proteomics in isoform detection, we developed IsoFrac, a computational pipeline that resolves protein isoforms based on their migration profiles across gel fractions. This approach enabled the identification of [~]45,000 full-length transcripts, [~]32,000 ORFs, and [~]16,000 distinct protein isoforms. Comparative analyses revealed widespread translation of alternative transcripts and uncovered proteolytic processing as a major, underappreciated source of proteome complexity. Our results establish a scalable framework for isoform-resolved proteogenomics and provide a reference resource for studying the molecular diversity encoded by the human genome.

systems biology↗

bioRxiv2020

Extensive Genetic Diversity and Host Range of Rodent-borne Coronaviruses

To better understand the genetic diversity, host association and evolution of coronaviruses (CoVs) in China we analyzed a total of 696 rodents encompassing 16 different species sampled from Zhejiang and Yunnan provinces. Based on the reverse transcriptase PCR-based CoV screening CoVs of fecal samples and subsequent sequence analysis of the RdRp gene, we identified CoVs in diverse rodent species, comprising Apodemus agrarius, Apodemus latronum, Bandicota indica, Eothenomys miletus, E. eleusis, Rattus andamanesis, Rattus norvegicus, and R. tanezumi. Apodemus chevrieri was a particularly rich host, harboring 25 rodent CoVs. Genetic and phylogenetic analysis revealed the presence of three groups of CoVs carried by a range of rodents that were closely related to the Lucheng Rn rat coronavirus (LRNV), China Rattus coronavirus HKU24 (ChRCoV_HKU24) and Longquan Rl rat coronavirus (LRLV) identified previously. One newly identified A. chevrieri-associated virus closely related to LRNV lacked an NS2 gene. This virus had a similar genetic organization to AcCoV-JC34, recently discovered in the same rodent species in Yunnan, suggesting that it represents a new viral subtype. Notably, additional variants of LRNV were identified that contained putative nonstructural NS2b genes located downstream of the NS2 gene that were likely derived from the host genome. Recombination events were also identified in the ORF1a gene of Lijiang-71. In sum, these data reveal the substantial genetic diversity and genomic complexity of rodent-borne CoVs, and greatly extend our knowledge of these major wildlife virus reservoirs.

genetics↗

bioRxiv2019

A CLEAR pipeline for direct comparison of circular and linear RNA expression

Sequences of circular RNAs (circRNAs) produced from back-splicing of exon(s) completely overlap with sequences from cognate linear RNAs transcribed from the same gene loci with the exception of their back-splicing junction (BSJ) sites. Examination of global circRNA expression from RNA-seq datasets generally relies on the detection of RNA-seq fragments spanning BSJ sites, but a direct comparison of circular and linear RNA expression from the same gene loci in a genome-wide manner has remained challenging. This is because quantification of BSJ fragments differs from that of linear RNA expression that uses normalized RNA-seq fragments mapped to the whole gene bodies. Here, we have developed a computational pipeline for circular and linear RNA expression analysis from ribosomal-RNA depleted RNA-seq (CLEAR, https://github.com/YangLab/CLEAR). A new quantitation parameter, FPB (fragments per billion mapped bases), is applied to evaluate circular and linear RNA expression individually by fragments mapped to circRNA-specific BSJ sites or to linear RNA-specific splicing junction (SJ) sites. Then, circular and linear RNA expression are directly compared by dividing FPBcirc by FPBlinear to generate a CIRCscore, which indicates the relative circRNA expression using linear RNA expression as the background. Highly-expressed circRNAs with low cognate linear RNA expression background can be identified for further investigation.

bioinformatics↗