gcaPDA: a haplotype-resolved diploid assembler.

Background: Generating chromosome-scale haplotype resolved assembly is important for functional studies. However, current de novo assemblers are either haploid assemblers that discard allelic information, or diploid assemblers that can only tackle genomes of low complexity.

Results: Here, Using robust programs, we build a diploid genome assembly pipeline called gcaPDA (gamete cells assisted Phased Diploid Assembler), which exploits haploid gamete cells to assist in resolving haplotypes.

Potential of fecal microbiota for detection and postoperative surveillance of colorectal cancer.

Background: Colorectal cancer (CRC) is one of the most common cancers. In recent studies, the gut microbiota has been reported to be potentially involved in aggravating or favoring CRC development. However, little is known about the microbiota composition in CRC patients after treatment.

Proteomics study of colorectal cancer and adenomatous polyps identifies TFR1, SAHH, and HV307 as potential biomarkers for screening.

Colorectal cancer (CRC) is a malignant tumour with high morbidity and mortality worldwide. Efficient screening strategies for CRC and pre-cancerous lesions can promote early medical intervention and treatment, thereby reducing morbidity and mortality. Proteins are generally considered key biomarkers of cancer.

Serum Magnesium and Fractional Exhaled Nitric Oxide in Relation to the Severity in Asthma-Chronic Obstructive Pulmonary Disease Overlap.

Serum concentrations of magnesium and manganese may be associated with increased chronic obstructive pulmonary disease exacerbation risk. However, associations with other aspects of asthma-chronic obstructive pulmonary disease overlap, pulmonary function test results and health status, have been studied less extensively. The aim of this study was to investigate the associations between serum concentrations of trace elements and T lymphocyte subsets, FeNO, and COPD-related questionnaire scores in individuals with ACO and the potential impact of these parameters on lung function.

Clinical application and evaluation of metagenomic next-generation sequencing in suspected adult central nervous system infection.

Background: Accurate etiology diagnosis is crucial for central nervous system infections (CNS infections). The diagnostic value of metagenomic next-generation sequencing (mNGS), an emerging powerful platform, remains to be studied in CNS infections.

Methods: We conducted a single-center prospective cohort study to compare mNGS with conventional methods including culture, smear and etc.

Diagnostic Performance of Donor-Derived Plasma Cell-Free DNA Fraction for Antibody-Mediated Rejection in Post Renal Transplant Recipients: A Prospective Observational Study.

Objective: To evaluate the diagnostic performance of donor-derived plasma cell-free DNA (cfDNA) in discriminating antibody-mediated rejection (ABMR) or donor-specific antibodies (DSA) without histological lesions in kidney allograft recipients.

Methods: In this prospective single center observational study, we enrolled kidney allograft recipients between November, 2016 and September, 2017 at the First Affiliated Hospital of Sun Yat-sen University. Kidney allograft recipients with ABMR, DSA but no histological lesions or negative DSA, and stable renal function were included.

STS-NLSP: A Network-Based Label Space Partition Method for Predicting the Specificity of Membrane Transporter Substrates Using a Hybrid Feature of Structural and Semantic Similarity.

Membrane transport proteins play crucial roles in the pharmacokinetics of substrate drugs, the drug resistance in cancer and are vital to the process of drug discovery, development and anti-cancer therapeutics. However, experimental methods to profile a substrate drug against a panel of transporters to determine its specificity are labor intensive and time consuming. In this article, we aim to develop an multi-label classification approach to predict whether a substrate can specifically recognize one of the 13 categories of drug transporters ranging from ATP-binding cassette to solute carrier families using both structural fingerprints and chemical ontologies information of substrates.

Prevalence of hereditary breast and ovarian cancer (HBOC) predisposition gene mutations among 882 HBOC high-risk Chinese individuals.

Identification of deleterious variants in hereditary breast and ovarian cancer (HBOC) susceptibility genes allows for increased clinical surveillance and early detection, and could predict the response to poly (ADP-ribose) polymerase (PARP) inhibitor in patients with advanced ovarian carcinomas. To determine the prevalence and clinical prediction factors for HBOC syndrome, 882 selected individuals underwent multigene panel testing for HBOC risk assessment during the period from January 2015 to March 2018. Overall, 176 deleterious mutations were observed in 19.

Germline and somatic mutations of multi-gene panel in Chinese patients with epithelial ovarian cancer: a prospective cohort study.

Background: Multiple targeted gene sequencing is seldom performed in both germline and somatic testing for ovarian cancer. This study is to evaluate the specific genetic alterations, including both somatic and germline mutations, in Chinese patients with epithelial ovarian cancer (EOC) in a prospective cohort study.

Materials And Methods: Mutations in a customed 21-gene panel that included BRCA1, BRCA2, and 19 other tumor suppressor genes related to homologous recombination (HR) deficiency or non-HR deficiency were detected by targeted exon capture and next-generation sequencing (NGS) technology across all coding exons and exon-intron (±20 base pairs) boundaries.

Circulating tumor DNA detection is correlated to histologic types in patients with early-stage non-small-cell lung cancer.

Objectives: Circulating tumor DNA (ctDNA) testing in plasma in patients with non-small-cell lung cancer (NSCLC) has the potential to be a supplemental or surrogate tool for tissue biopsy. Detection of genomic abnormalities in ctDNA and their association with clinical characteristics in early-stage NSCLC need to be clarified.

Materials And Methods: Here, we comprehensively analyzed gene variations of 48 tumor tissues and 48 matched preoperative (pre-op) plasma and 25 postoperative (post-op) plasma from early-stage NSCLC patients using a targeted 546 genes capture-based next generation sequencing (NGS) assay.

Universal screening for Lynch syndrome in a large consecutive cohort of Chinese colorectal cancer patients: High prevalence and unique molecular features.

The prevalence of Lynch syndrome (LS) varies significantly in different populations, suggesting that ethnic features might play an important role. We enrolled 3330 consecutive Chinese patients who had surgical resection for newly diagnosed colorectal cancer. Universal screening for LS was implemented, including immunohistochemistry for mismatch repair (MMR) proteins, BRAF mutation test and germline sequencing.

Next generation sequencing-based molecular profiling of lung adenocarcinoma using pleural effusion specimens.

Background: Molecular profiling of non-small cell lung cancer (NSCLC) is essential for therapeutic decision-making. Pleural effusion obtained by a non-invasive, repeatable procedure may provide an opportunity for molecular profiling and thereby possibly provide information enabling targeted therapy. In this study, we aimed to evaluate the diagnostic performance of pleural effusion as a specimen for molecular analysis.

Comprehensive targeted super-deep next generation sequencing enhances differential diagnosis of solitary pulmonary nodules.

Background: A non-invasive method to predict the malignancy of surgery-candidate solitary pulmonary nodules (SPN) is urgently needed.

Methods: Super-depth next generation sequencing (NGS) of 35 paired tissues and plasma DNA was performed as an attempt to develop an early diagnosis approach.

Results: Only ~6% of malignant nodule patients had driver mutations in the circulating tumour DNA (ctDNA) with >10,000-fold sequencing depth, and the concordance of mutation between tDNA and ctDNA was 3.

Development and clinical validation of a circulating tumor DNA test for the identification of clinically actionable mutations in nonsmall cell lung cancer.

Molecular analysis of potentially actionable mutations has become routine practice in oncological pathology. However, testing a wide range of oncogenes and mutations can be technically challenging because of limitations associated with tumor biopsy. Circulating tumor DNA (ctDNA) is a potential tool for the noninvasive profiling of tumors.

Systematic identification of cancer-related long noncoding RNAs and aberrant alternative splicing of quintuple-negative lung adenocarcinoma through RNA-Seq.

Objectives: Lung adenocarcinoma (LUAD) is a common subtype of non-small cell lung cancer prevalent in Asia. There is a dearth of understanding regarding the transcriptome landscape of LUAD without primary known driver mutations. In this study, LUAD samples without well-known driver mutations occurring in EGFR, KRAS, ALK, ROS1 or RET (quintuple-negative) were used for transcriptome study with a focus on long noncoding RNAs (lncRNAs), alternative splicing and gene fusions.

A targeted next-generation sequencing method for identifying clinically relevant mutation profiles in lung adenocarcinoma.

Molecular profiling of lung cancer has become essential for prediction of an individual's response to targeted therapies. Next-generation sequencing (NGS) is a promising technique for routine diagnostics, but has not been sufficiently evaluated in terms of feasibility, reliability, cost and capacity with routine diagnostic formalin-fixed, paraffin-embedded (FFPE) materials. Here, we report the validation and application of a test based on Ion Proton technology for the rapid characterisation of single nucleotide variations (SNVs), short insertions and deletions (InDels), copy number variations (CNVs), and gene rearrangements in 145 genes with FFPE clinical specimens.

Rapid diagnosis of Propionibacterium acnes infection in patient with hyperpyrexia after hematopoietic stem cell transplantation by next-generation sequencing: a case report.

Background: The rapid determination of pathogenic agent is very important to clinician for guiding their clinical medication. However, current diagnostic methods are of limitation in many aspects, such as detecting range, time-consuming, specificity and sensitivity. In this report, we apply our new-developing pathogen detection method to clarify that Propionibacterium acnes is the causative agent of a two-year-old boy with juvenile myelomonocytic leukemia presenting clinical symptoms including serious rash and hyperpyrexia while traditional clinical methods of diagnosis fail to detect the pathogenic agent and multiple antimicrobial drugs are almost ineffective Propionibacterium acnes is confirmed to be the infectious agent by quantitative real-time polymerase chain reaction.

Frequent alterations in cytoskeleton remodelling genes in primary and metastatic lung adenocarcinomas.

The landscape of genetic alterations in lung adenocarcinoma derived from Asian patients is largely uncharacterized. Here we present an integrated genomic and transcriptomic analysis of 335 primary lung adenocarcinomas and 35 corresponding lymph node metastases from Chinese patients. Altogether 13 significantly mutated genes are identified, including the most commonly mutated gene TP53 and novel mutation targets such as RHPN2, GLI3 and MRC2.

Direct ChIP-bisulfite sequencing reveals a role of H3K27me3 mediating aberrant hypermethylation of promoter CpG islands in cancer cells.

The model describing that aberrant CpG island (CGI) methylation leads to repression of tumour suppressor genes in cancers has been influential, but it remains unclear how such aberrancy is induced. Recent studies provided clues indicating that promoter hypermethylation in cancers might be associated with PRC target genes. Here, we used ChIP-BS-seq to examine methylation of the DNA fragments precipitated by the antibodies to both H3K27me3 and H3K4me3 histone modifications.

Single-base resolution maps of cultivated and wild rice methylomes and regulatory roles of DNA methylation in plant gene expression.

Background: DNA methylation plays important biological roles in plants and animals. To examine the rice genomic methylation landscape and assess its functional significance, we generated single-base resolution DNA methylome maps for Asian cultivated rice Oryza sativa ssp. japonica, indica and their wild relatives, Oryza rufipogon and Oryza nivara.

A systematic analysis on DNA methylation and the expression of both mRNA and microRNA in bladder cancer.

Background: DNA methylation aberration and microRNA (miRNA) deregulation have been observed in many types of cancers. A systematic study of methylome and transcriptome in bladder urothelial carcinoma has never been reported.

Methodology/principal Findings: The DNA methylation was profiled by modified methylation-specific digital karyotyping (MMSDK) and the expression of mRNAs and miRNAs was analyzed by digital gene expression (DGE) sequencing in tumors and matched normal adjacent tissues obtained from 9 bladder urothelial carcinoma patients.

The DNA methylome of human peripheral blood mononuclear cells.

DNA methylation plays an important role in biological processes in human health and disease. Recent technological advances allow unbiased whole-genome DNA methylation (methylome) analysis to be carried out on human cells. Using whole-genome bisulfite sequencing at 24.

Identification of vaccine candidates from differentially expressed outer membrane proteins of Vibrio alginolyticus in response to NaCl and iron limitation.

Vibrio alginolyticus is the etiological agent that causes great losses in aquacultures and clinical emanating cases in humans. Identification of highly efficient vaccine candidates to control V. alginolyticus infection has been highly concerned since vaccines offer a powerful approach to provide efficient protection from bacterial infections.