Nature子刊EJHGNGS診斷指南

1、 Nature 子刊 EJHG|NGS診斷指南發(fā)布背景介紹:EJHG (European journal of human genetics 屬于 Nature 子刊, 近日發(fā)布了“ Guidelines for diagnostic next-generation sequencing”,即 NGS 診斷指南。小編整理出來與大家共享,希望能得到一些啟發(fā),歡迎各位朋 友批評指正。 STATEMENT01: NGS should not be transferred to clinical practicewithout anacceptable validation of the tests

2、according to theemerging guidelines. 沒有遵循指南驗(yàn)證的檢測不能用于臨床 STATEMENT02: The laboratory has to make clear whether the testthat is being offered may be used to exclude a diagnosis, or toconfirm a diagnosis. 檢測機(jī)構(gòu)必須闡明提供的檢測是用于診斷還是篩查 STATEMENT03: The aim and the utility of the test or assay shouldbe discussed

3、 at the beginning of the validation and a summaryshould be included in the validation report. 檢測的目的與相關(guān)設(shè)備必須在檢測前明確,并需要寫進(jìn)最終報(bào)告 STATEMENT04: When a laboratory is considering introducingNGS in diagnostics, it first has to consider the diagnostic yield. 在進(jìn)行 NGS 檢測前,必須考慮已知診斷率 STATEMENT05: For diagnostic pur

4、pose, only genes with a known(ie,published and confirmed relationship between the aberrantgenotype and the pathology should be included in the analysis. 如果目的是診斷,相關(guān)基因必須為明確與疾病相關(guān) STATEMENT06: For the sake of comparison, to avoid irresponsible testing, for the benefit of the patients, core disease gene

5、lists should be established by the clinical and laboratory experts. 與疾病相關(guān)的最核心基因列表, 必須由臨床與檢測機(jī)構(gòu)的專家共同決定, 目的 是為了有可比性和完善性 STATEMENT07: A simple rating system on the basis of coverageand diagnostic yield, should allow comparison of the diagnostictesting offer between laboratories. 至少提供最基本的質(zhì)控和檢測結(jié)果,以便不同檢測機(jī)構(gòu)

6、之間有可比性 STATEMENT08: The laboratory has to provide for each NGS testthe following: the diseases it targets, the name of the genestested,their reportable range, the analytical sensitivity and specificity,and,if possible, the diseases not relevant to the clinical phenotypethatcould be caused by mutatio

7、ns in the tested genes. 檢測機(jī)構(gòu)必須提供:檢測疾病列表,相關(guān)基因,基因檢測范圍,敏感度與專一 度(可選:其他與表型無關(guān)的致病突變 STATEMENT09: The analysis pipeline of diagnostic laboratoriesshould focus on the gene panel under investigation in order to avoidthe chance of secondary findings, and be validated accordingly. 檢測重點(diǎn)應(yīng)該放在與疾病最相關(guān)的基因上,并做相關(guān)驗(yàn)證,盡量避免

8、分析無關(guān) 基因 STATEMENT10: Laboratories should provide information on thechance of unsolicitedfindings. 不明確的突變要做詳細(xì)說明(如隱性單雜合點(diǎn) STATEMENT11: If a clinical center or a laboratory decides to offerpatients an opt-in, opt-out protocol to get carrier status forunrelated diseases and secondary findings all the log

9、istics need tobe covered. 如果要報(bào)道與表型無關(guān)的突變, 除了要符合相應(yīng)法規(guī), 還要預(yù)先征得患者同意。 STATEMENT12: The local policy about dissemination of unsolicited and secondary findingsshould be clear for the patient. 患者需要明確當(dāng)?shù)仃P(guān)于報(bào)道檢測之外突變的法規(guī) STATEMENT13:It is recommended to provide a written information leaflet or online availableinfo

10、rmation for patients. 建議提供患者手寫或在線版的知情書 STATEMENT14: All NGS quality metrics used in diagnosticsprocedures should be accurately described. 所有質(zhì)控參數(shù)必須精確提供 STATEMENT15: The diagnostic laboratory has to implement astructured database for relevant quality measures for (itheplatform, (ii all assays, and (ii

11、i all samples processed. 所有相關(guān)質(zhì)控結(jié)果必須整理成數(shù)據(jù)庫(平臺,檢測,樣本 STATEMENT17: Accuracy and precision should be part of thegeneral platform validation, and the work does not have to berepeated for individual methods or tests. 保證平臺的準(zhǔn)確性與精確性,避免不必要的重復(fù)實(shí)驗(yàn) STATEMENT18: The bioinformatics pipeline must be tailored forthe

12、technical platform used. 生物信息學(xué)流程必須適合技術(shù)平臺 STATEMENT19: Analytical sensitivity and analytical specificitymust be established separately for each type of variant duringpipeline validation. 不同種類的變異類型的檢測準(zhǔn)確性必須分別分析(snv , indel STATEMENT20: The diagnostic laboratory has to validate all partsof the bioinform

13、aticspipeline (public domain tools or commercialsoftware packages with standard data sets whenever relevantchanges (new releases are implemented. 當(dāng)流程做改動時(shí),必須用標(biāo)準(zhǔn)數(shù)據(jù)檢驗(yàn) STATEMENT21: The diagnostic laboratory has to implement/use astructured database for all relevant variants with currentannotations. 必須建立

14、本地變異數(shù)據(jù)庫(用于檢驗(yàn)變異真實(shí)性 STATEMENT22: The diagnostic laboratory has to take steps forlong-term storage of all relevant data sets. 需要做長期存儲數(shù)據(jù)的準(zhǔn)備(bam , fastq STATEMENT23: The reportable range, that is, the portion of theclinical target for which reliable calls can be generated, has tobedefined during the test

15、 development and should be available totheclinician (either in the report or communicated digitally. 檢測基因的范圍必須提前確定并告知臨床醫(yī)師 STATEMENT24: The requirements for reportable range dependon the aim of the assay. 檢測范圍需要根據(jù)檢測目的決定 STATEMENT25: Whenever major changes are made to the test,quality parameters have

16、to be checked, and samples have to bere-run. The laboratory should define beforehand what kind ofsamples and the number of cases that have to be assayed wheneverthe method is updated or upgraded. 當(dāng)檢測有較大改動時(shí),所有質(zhì)控參數(shù)必須檢查,樣本必須做對照實(shí)驗(yàn),并且測 試樣本的性質(zhì)與數(shù)量必須提前確定。 STATEMENT26: The report of a NGS assay should summar

17、ize thepatients identification and diagnosis, a brief description of the test,a summary of results, and the major findings on one page. 檢測報(bào)告應(yīng)該在一頁之內(nèi)包括如下內(nèi)容:1. 患者身份及診斷信息, 2. 檢測的 概括性描述, 3. 結(jié)果總結(jié), 4. 結(jié)論 STATEMENT27: A local policy, in line with international recommendations, for reportinggenomic variants

18、should be established anddocumented by the laboratory prior to providing analysis of this type. 本地對基因檢測報(bào)告的政策法規(guī)必須符合國際標(biāo)準(zhǔn)并在提供相關(guān)檢測服務(wù)之 前建立 STATEMENT28: Data on UVs have to be collected, with the aim toeventually classify these variants definitively. 意義不明確的結(jié)果必須收集,為了之后確診的可能 STATEMENT29: Laboratories should

19、 have a clearly definedprotocol for addressing unsolicited and secondary findings priorto launching the test. 檢測機(jī)構(gòu)對未明確及次級發(fā)現(xiàn)的處理方案必須提前明確 STATEMENT30: The laboratory is not expected to re-analyze olddata systematically and report novel findings, not even when thecore disease gene panel changes. 檢測機(jī)構(gòu)不應(yīng)該

20、被要求反復(fù)分析檢測報(bào)告,即使核心基因 penal 數(shù)量有改變, 即只報(bào)道當(dāng)前最明確的結(jié)果(但特殊情況除外 STATEMENT31: To be able to manage disease variants, thelaboratory has to set up a local variant database for thedifferentdiseases for which testing is offered on a clinical basis. 為了便于管理,檢測機(jī)構(gòu)應(yīng)該建立本地以臨床診斷疾病為分類的變異數(shù)據(jù)庫 STATEMENT32: A diagnostic test is

21、 any test directed towardanswering a clinical question related to a medical condition of apatient. 診斷檢測必須與患者疾病相關(guān)的臨床問題直接相關(guān) STATEMENT33: A research test is hypothesis driven and theoutcome may have limited clinical relevance for a patient enrolledin the project. 研究實(shí)驗(yàn)以假設(shè)為前提,結(jié)果可不以臨床為導(dǎo)向。 STATEMENT34: The results of a diagnostic test, particularly byanalysis of a whole exome orgenome, can be hypot