A practical guide to interpreting germline variants that drive hematopoietic malignancies,bone marrow failure,and chronic cytopenias

PurposeThe American College of Medical Genetics and Genomics and the Association for Molecular Pathology guidelines for germline variant interpretation are implemented as a broad framework by standardizing variant interpretation. These rules were designed to be specified, but this process has not been performed for most of the 200 genes associated with inherited hematopoietic malignancies, bone marrow failure, and cytopenias. Because guidelines on how to perform these gene specifications are lacking, variant interpretation is less reliable and reproducible.MethodsWe have used a variety of methods such as calculations of minor allele frequencies, quasi-case–control studies to establish thresholds, proband counting, and plotting of receiver operating characteristic curves to compare different in silico prediction tools to design recommendations for variant interpretation.ResultsWe herein provide practical recommendations for the creation of thresholds for minor allele frequencies, in silico predictions, counting of probands, identification of functional domains with minimal benign variation, use of constraint Z-scores and functional evidence, prediction of nonsense-mediated decay, and assessment of phenotype specificity.ConclusionThese guidelines can be used by anyone interpreting variants associated with inherited hematopoietic malignancies, bone marrow failure, and cytopenias to develop criteria for reliable, accurate, and reproducible germline variant interpretation.     

Checklist for gene/disease‐specific variation database curators to enable ethical data management

Databases with variant and phenotype information are essential for advancing research and improving the health and welfare of individuals. These resources require data to be collected, curated, and shared among relevant specialties to maximize impact. The increasing generation of data which must be shared both nationally and globally for maximal effect presents important ethical and privacy concerns. Database curators need to ensure that their work conform to acceptable ethical standards. A Working Group of the Human Variome Project had the task of updating and streamlining ethical guidelines for locus‐specific/gene variant database curators. In this article, we present practical and achievable steps which should assist database curators in carrying out their responsibilities within acceptable ethical norms.     

加州理工大学图书馆数据监管需求评估项目的启示和思考

介绍数据监管的内涵，阐述加州州立理工大学图书馆数据监管需求评估项目，分析项目成果，指出该项目对国内图书馆的启示，即开展科研数据服务营销推广、数据监管培训服务、通过合作实现高质量的数据监管服务等。     

Collection,verification, sharing and dissemination of data: the CONTRAST experience

The scientific community is charged with growing demands regarding the management of project data and outputs and the dissemination of key results to various stakeholders. We discuss experiences and lessons from CONTRAST, a multidisciplinary alliance that had been funded by the European Commission over a 4-year period, in order to optimize schistosomiasis control and transmission surveillance in sub-Saharan Africa. From the start, project partners from Europe and Africa set out an ambitious goal: to sample data following standard protocols at all field sites and then sharing the data in a way that would enable all project partners to have access through a password-protected Internet-based data portal. This required anonymous agreement on several common standardized sample forms, ranging from the mundane but important issue of using the same units of measurement to more complex challenges, for instance agreeing on the same protocols for double-treatment of praziquantel in different settings. With the experiences gained by the CONTRAST project, this paper discusses issues of data management and sharing in research projects in the light of the current donor demand, and offers advice and specific suggestions for similar interdisciplinary research projects.     

Genetic Variations and Diseases in UniProtKB/Swiss‐Prot: The Ins and Outs of Expert Manual Curation

During the last few years, next‐generation sequencing (NGS) technologies have accelerated the detection of genetic variants resulting in the rapid discovery of new disease‐associated genes. However, the wealth of variation data made available by NGS alone is not sufficient to understand the mechanisms underlying disease pathogenesis and manifestation. Multidisciplinary approaches combining sequence and clinical data with prior biological knowledge are needed to unravel the role of genetic variants in human health and disease. In this context, it is crucial that these data are linked, organized, and made readily available through reliable online resources. The Swiss‐Prot section of the Universal Protein Knowledgebase (UniProtKB/Swiss‐Prot) provides the scientific community with a collection of information on protein functions, interactions, biological pathways, as well as human genetic diseases and variants, all manually reviewed by experts. In this article, we present an overview of the information content of UniProtKB/Swiss‐Prot to show how this knowledgebase can support researchers in the elucidation of the mechanisms leading from a molecular defect to a disease phenotype.     

@Note: A workbench for Biomedical Text Mining

Biomedical Text Mining (BioTM) is providing valuable approaches to the automated curation of scientific literature. However, most efforts have addressed the benchmarking of new algorithms rather than user operational needs. Bridging the gap between BioTM researchers and biologists’ needs is crucial to solve real-world problems and promote further research.We present @Note, a platform for BioTM that aims at the effective translation of the advances between three distinct classes of users: biologists, text miners and software developers. Its main functional contributions are the ability to process abstracts and full-texts; an information retrieval module enabling PubMed search and journal crawling; a pre-processing module with PDF-to-text conversion, tokenisation and stopword removal; a semantic annotation schema; a lexicon-based annotator; a user-friendly annotation view that allows to correct annotations and a Text Mining Module supporting dataset preparation and algorithm evaluation.@Note improves the interoperability, modularity and flexibility when integrating in-home and open-source third-party components. Its component-based architecture allows the rapid development of new applications, emphasizing the principles of transparency and simplicity of use. Although it is still on-going, it has already allowed the development of applications that are currently being used.     

iSchools成员院校数据监护课程调查

数据监护是科学管理数据并提供数据增值服务的重要手段,学院数据监护教育是培养专业数据监护人才的重要途径。调研了66所iSchools成员院校的数据监护课程,获得数据监护相关课程的课程内容形成课程内容标签,并结合科学数据管理生命周期,分析不同国家、不同课程等级以及科学数据管理生命周期不同阶段的课程主题,从课程内容角度进一步了解数据监护课程现状,对国内相关院校开设类似课程提供科学的依据。     

中药内外合治溃疡性结肠炎临床观察

目的观察中药内外合治溃疡性结肠炎的临床疗效。方法将80例患者随即分为治疗组与对照组各40例。治疗组给予止溃结汤内服和愈结汤保留灌肠治疗,对照组予柳氮磺胺吡啶(SASP)治疗。1个月为1个疗程,治疗3个疗程后观察疗效。结果治疗组总有效率优于对照组(P<0.05)。结论中药止溃结汤内服和愈结汤保留灌肠治疗溃疡性结肠炎疗效显著。     

红景天根腐病的防治研究

对新疆红景天根腐病病因调查表明,低海拔区种植、7~8月高温、土壤湿度大(浇水多)亦是红景天根腐病流行的主要原因之一。中耕时适当扒土使红景天根茎部裸出地面和人工摘除花芽等措施可以减轻根腐病的危害。室内及田间药物防治试验表明:多菌灵、多菌灵 福美双混合剂600倍对红景天根腐病的防治效果显著,分别达到82.12%和85.34%。     

The Gene Curation Coalition: A global effort to harmonize gene–disease evidence resources

PurposeSeveral groups and resources provide information that pertains to the validity of gene–disease relationships used in genomic medicine and research; however, universal standards and terminologies to define the evidence base for the role of a gene in disease and a single harmonized resource were lacking. To tackle this issue, the Gene Curation Coalition (GenCC) was formed.MethodsThe GenCC drafted harmonized definitions for differing levels of gene–disease validity on the basis of existing resources, and performed a modified Delphi survey with 3 rounds to narrow the list of terms. The GenCC also developed a unified database to display curated gene–disease validity assertions from its members.ResultsOn the basis of 241 survey responses from the genetics community, a consensus term set was chosen for grading gene–disease validity and database submissions. As of December 2021, the database contained 15,241 gene–disease assertions on 4569 unique genes from 12 submitters. When comparing submissions to the database from distinct sources, conflicts in assertions of gene–disease validity ranged from 5.3% to 13.4%.ConclusionTerminology standardization, sharing of gene–disease validity classifications, and resolution of curation conflicts will facilitate collaborations across international curation efforts and in turn, improve consistency in genetic testing and variant interpretation.