我国罗布麻种质资源研究利用现状

罗布麻(Apocynum venetum)是一种世界上稀有的野生植物。其叶可以入药,也可以制保健茶。该文简介了罗布麻的发现、分布和植物学分类,并对罗布麻种质资源多样性和耐盐性研究以及罗布麻的开发利用进行了详细综述。旨在为罗布麻耐盐机理、种质资源保护以及定向育种研究提供理论依据和参考,并呼吁广大同行加强对罗布麻种质资源的保护工作。

A novel CD4+CTL subtype characterized by chemotaxis and inflammation is involved in the pathogenesis of Graves’orbitopathy

Graves*orbitopathy(GO),the most severe manifestation of Graves'hyperthyroidism(GH),is an autoimmune-mediated inflammatory disorder,and treatments often exhibit a low efficacy.CD4+T cells have been reported to play vital roles in GO progression.To explore the pathogenic CD4-f T cell types that drive GO progression,we applied single-cell RNA sequencing(scRNA-Seq),T cell receptor sequencing(TCR-Seq),flow cytometry,immunofluorescence and mixed lymphocyte reaction(MLR)assays to evaluate CD4+T cells from GO and GH patients.scRNA-Seq revealed the novel GO-spedfic cell type CD4+cytotoxic T lymphocytes(CTLs),which are characterized by chemotactic and inflammatory features.The clonal expansion of this CD4+CTL population,as demonstrated by TCR-Seq,along with their strong cytotoxic response to autoantigens,localization in orbital sites,and potential relationship with disease relapse provide strong evidence for the pathogenic roles of GZMB and IFN-y-secreting CD4+CTLs in GO.Therefore,cytotoxic pathways may become potential therapeutic targets for GO.

MSIsensor-pro: Fast, Accurate, and Matched-normal-sample-free Detection of Microsatellite Instability

Microsatellite instability(MSI)is a key biomarker for cancer therapy and prognosis.Traditional experimental assays are laborious and time-consuming,and next-generation sequencingbased computational methods do not work on leukemia samples,paraffin-embedded samples,or patient-derived xenografts/organoids,due to the requirement of matched normal samples.Herein,we developed MSIsensor-pro,an open-source single sample MSI scoring method for research and clinical applications.MSIsensor-pro introduces a multinomial distribution model to quantify polymerase slippages for each tumor sample and a discriminative site selection method to enable MSI detection without matched normal samples.We demonstrate that MSIsensor-pro is an ultrafast,accurate,and robust MSI calling method.Using samples with various sequencing depths and tumor purities,MSIsensor-pro significantly outperformed the current leading methods in both accuracy and computational cost.MSIsensor-pro is available at https://github.com/xjtu-omics/msisensor-pro and free for non-commercial use,while a commercial license is provided upon request.

Mako:A Graph-based Pattern Growth Approach to Detect Complex Structural Variants

Complex structural variants(CSVs) are genomic alterations that have more than two breakpoints and are considered as the simultaneous occurrence of simple structural variants.However,detecting the compounded mutational signals of CSVs is challenging through a commonly used model-match strategy.As a result,there has been limited progress for CSV discovery compared with simple structural variants.Here,we systematically analyzed the multi-breakpoint connection feature of CSVs,and proposed Mako,utilizing a bottom-up guided model-free strategy,to detect CSVs from paired-end short-read sequencing.Specifically,we implemented a graph-based pattern growth approach,where the graph depicts potential breakpoint connections,and pattern growth enables CSV detection without pre-defined models.Comprehensive evaluations on both simulated and real datasets revealed that Mako outperformed other algorithms.Notably,validation rates of CSVs on real data based on experimental and computational validations as well as manual inspections are around 70%,where the medians of experimental and computational breakpoint shift are 13 bp and 26 bp,respectively.Moreover,the Mako CSV subgraph effectively characterized the breakpoint connections of a CSV event and uncovered a total of 15 CSV types,including two novel types of adjacent segment swap and tandem dispersed duplication.Further analysis of these CSVs also revealed the impact of sequence homology on the formation of CSVs.Mako is publicly available at https://github.com/xjtu-omics/Mako.

JAX-CNV:A Whole-genome Sequencing-based Algorithm for Copy Number Detection at Clinical Grade Level

We aimed to develop a whole-genome sequencing(WGS)-based copy number variant(CNV)calling algorithm with the potential of replacing chromosomal microarray assay(CMA)for clinical diagnosis.JAX-CNV is thus developed for CNV detection from WGS data.The performance of this CNV calling algorithm was evaluated in a blinded manner on 31 samples and compared to the 112 CNVs reported by clinically validated CMAs for these 31 samples.The result showed that JAX-CNV recalled 100%of these CNVs.Besides,JAX-CNV identified an average of 30 CNVs per individual,representing an approximately seven-fold increase compared to calls of clinically validated CMAs.Experimental validation of 24 randomly selected CNVs showed one false positive,i.e.,a false discovery rate(FDR)of 4.17%.A robustness test on lowercoverage data revealed a 100%sensitivity for CNVs larger than 300 kb(the current threshold for College of American Pathologists)down to 10×coverage.For CNVs larger than 50 kb,sensitivities were 100%for coverages deeper than 20×,97%for 15×,and 95%for 10×.We developed a WGS-based CNV pipeline,including this newly developed CNV caller JAX-CNV,and found it capable of detecting CMA-reported CNVs at a sensitivity of 100%with about a FDR of 4%.We propose that JAX-CNV could be further examined in a multi-institutional study to justify the transition of first-tier genetic testing from CMAs to WGS.JAX-CNV is available at https://github.com/TheJacksonLaboratory/JAX-CNV.