Hepatocellular carcinoma (HCC) is one of the most common solid tumors worldwide, and is particularly prevalent in Asia, being the third most common cause of cancer-related death. Hepatitis B virus (HBV) is a major etiologic agent, leading to an increased risk of developing HCC, in particular those with acute liver disease and cirrhosis. The Asian Cancer Research Group (ACRG) is an independent, not-for-profit company established to accelerate research and improve treatment for patients affected with the most commonly-diagnosed cancers in Asia. Bringing together pharmaceutical partners from Eli Lily, Merck, and Pfizer, with academic partners at Hong Kong University, National University of Singapore and BGI, with the aim to create one of the most extensive open pharmacogenomic cancer datasets known to date. With HBV being endemic in China and Southeast Asia, and high levels of HCC being a result, the ACRG have studied the events and effects of HBV integration in the HCC genome. To do this massively parallel sequencing in a cohort of 88 Chinese patients diagnosed with HCC who underwent curative primary hepatectomy or liver transplantation at Queen Mary Hospital (Pokfulam, Hong Kong) was carried out. Of these 81 were HBV-positive and 7 HBV-negative. All patients gave written informed consent to use both tumour (T) and non-tumour (N) liver tissues for the study and open sharing of the data. Genomic DNA was purified for at least 30-fold coverage paired-end (PE) sequencing, and PE reads were mapped on human reference genome (UCSC build hg19) and HBV (NC_003977). Two sequencing libraries with different insert size were constructed for each genomic DNA sample (200 bp and 800 bp). Paired end, 90bp read length sequencing was performed in the HiSeq 2000 sequencer according to Manufacturer’s instructions.
The results of this are published in Nature Genetics: doi: 10.1038/ng.2295.
Multidrug resistance (MDR)-encoding plasmids are considered major molecular vehicles responsible for transmission of antibiotic resistance genes among bacteria of the same or different species. Delineating the complete sequence of such plasmids could provide valuable insight into the evolution and transmission mechanisms underlying bacterial antibiotic resistance development. However, due to the presence of multiple repeats of IS elements, complete sequencing of MDR plasmids remains technically complicated, expensive and time-consuming.
Here, we demonstrate a rapid and efficient approach to obtain multiple MDR plasmid sequences through the use of the MinION nanopore sequencing platform, which is incorporated in a portable MinION device. By assembling the long sequencing reads generated by a single MinION run according to a rapid barcoding sequencing protocol, we obtained the complete sequence of 20 plasmids harbored by bacterial strains recovered from multiple samples. Importantly, single long reads covering a plasmid end-to-end were recorded, indicating that de novo assembly may be unnecessary if the single reads exhibit high accuracy.
This workflow represents a novel, convenient and cost effective approach for systematic assessment of the full range of MDR plasmids responsible for causing failure in antimicrobial treatment of bacterial infections, offering for the first time the opportunity to perform detailed molecular epidemiological studies to probe the evolutionary and transmission routes/mechanisms of MDR-encoding elements.
Psoriasis is a common and chronic inflammatory skin disease complicated by genetic-environmental interactions. Although genomic, transcriptomic and proteomic analyses have been performed to investigate the pathogenesis of psoriasis, the role of metabolites in psoriasis, particularly of lipids, remains unclear. Lipids not only comprise the bulk of the cellular membrane bilayers but also regulate a variety of biological processes, such as cell proliferation, apoptosis, immunity, angiogenesis and inflammation.
In this study, an untargeted lipidomics approach was used to study the lipid profiles in psoriasis and identify lipid metabolite signatures for psoriasis through ultra-performance liquid chromatography-quadrupole tandem mass spectrometry. Plasma samples from 90 participants (45 healthy and 45 psoriasis patients) were collected and detected. Statistical analysis was applied to find different features between the two subjects. In addition, ELISA was performed to examine differential expression lipids in psoriatic patient plasma. We finally identified several differential expression lipids including LPAs, LysoPCs, PIs, PCs and PAs, among these metabolites, LPAs, LysoPCs and PAs were significantly increased, while PCs and PIs were down-regulated in psoriasis group.