Biology subjects

Hui Zhang

Publications and source records attributed to Hui Zhang.

3 recordsLinked to original sources

bioRxiv2016

Multi-laboratory assessment of reproducibility, qualitative and quantitative performance of SWATH-mass spectrometry

Quantitative proteomics employing mass spectrometry has become an indispensable tool in basic and applied life science research. Methods based on data-dependent acquisition have proved extremely valuable for qualitative proteome analysis but historically have struggled to achieve reproducible quantitative data if large sample cohorts are comparatively analyzed. Targeted proteomics, most commonly implemented as selected reaction monitoring, has emerged as a powerful alternative and succeeded in providing a data independent approach for reproducible quantitative proteomics data but is limited in the number of proteins quantified. SWATH-MS is a recently introduced technique consisting of a data-independent acquisition and a targeted data analysis strategy that aims to maintain the favorable quantitative characteristics (accuracy, sensitivity, specificity) achieved in targeted proteomics but on the scale of thousands of proteins. While previous SWATH-MS studies have shown high intra-lab reproducibility, this has not been evaluated on an inter-lab basis. In this multi-laboratory evaluation study using data from 11 sites worldwide, we have demonstrated that using SWATH-MS we can consistently detect and quantify more than 4,000 proteins from HEK293 cells and that the quantitative protein data generated across laboratories is reproducible. Using synthetic peptide dilution series, we have shown that the sensitivity, dynamic range and reproducibility established with SWATH-MS methods are also uniformly achieved across labs. This study demonstrates that SWATH-MS is a reproducible and accurate technique that can be confidently deployed for large-scale protein quantification in life science research.

Biochemistry↗

bioRxiv2016

Characteristic arrangement of nucleosomes is predictive of chromatin interactions at kilobase resolution

High-throughput chromosome conformation capture technologies, such as Hi-C, have made it possible to survey 3D genome structure. However, the ability to obtain 3D profiles at kilobase resolution at low cost remains a major challenge. Therefore, we herein report a computational method to precisely identify chromatin interaction sites at kilobase resolution from MNase-seq data, termed chromatin interaction site detector (CISD), and a CISD-based chromatin loop predictor (CISD_loop) that predicts chromatin-chromatin interaction (CCI) from low-resolution Hi-C data. The methods are built on a hypothesis that CCIs result in a characteristic nucleosome arrangement pattern flanking the interaction sites. Accordingly, we show that the predictions of CISD and CISD_loop overlap closely with chromatin interaction analysis by paired-end tag sequencing (ChIA-PET) anchors and loops, respectively. Moreover, the methods trained in one cell type can be applied to other cell types with high accuracy. The validity of the methods was further supported by chromosome conformation capture (3C) experiments at 5kb resolution. Finally, we demonstrate that only modest amounts of MNase-seq and Hi-C data are sufficient to achieve ultrahigh resolution CCI map. The predictive power of CISD/CISD_loop supports the hypothesis that CCIs induce local nucleosome rearrangement and that the pattern may serve as probes for 3D dynamics of the genome. Thus, our method will facilitate precise and systematic investigations of the interactions between distal regulatory elements on a larger scale than hitherto have been possible.

Bioinformatics↗

bioRxiv2015

Mutation rate estimation for 15 autosomal STR loci in a large population from Mainland China

STR, short trandem repeats, is well known as a type of powerful genetic marker and widely used in studying human population genetics. Compared with the conventional genetic markers, the mutation rate of STR is higher. Additionally, the mutations of STR loci do not lead to genetic inconsistencies between the genotypes of parents and children; therefore, the analysis of STR mutation is more suited to assess the population mutation. In this study, we focused on 15 autosomal STR loci (D8S1179, D21S11, D7S820, CSF1PO, D3S1358, TH01, D13S317, D16S539, D2S1338, D19S433, vWA, TPOX, D18S51, D5S818, FGA). DNA samples from a total of 42416 unrelated healthy individuals (19037 trios) from the population of Mainland China collected between Jan 2012 and May 2014 were successfully investigated. In our study, the allele frequencies, paternal mutation rates, maternal mutation rates and average mutation rates were detected in the 15 STR loci. Furthermore, we also investigated the relationship between paternal ages, maternal ages, pregnant time, area and average mutation rate. We found that paternal mutation rate is higher than maternal mutation rate and the paternal, maternal, and average mutation rates have a positive correlation with paternal ages, maternal ages and times respectively. Additionally, the average mutation rates of coastal areas are higher than that of inland areas. Overall, these results suggest that the 15 autosomal STR loci can provide highly informative polymorphic data for population genetic assessment in Mainland China, as well as confirm and extend the application of STR analysis in population genetics.

Genetics↗