Sentieon应用之基因诊断公司
 
 
 

         Sentieon致力于解决生物信息数据分析中的速度与准确度瓶颈，通过算法的深度优化和企业级的软件工程，大幅度提升NGS数据处理的效率、准确度和可靠性。自2015年的初始版本开始，Sentieon推出了包括比对到变异检测在内的完整二次分析的解决方案，可用于胚系突变检测和体细胞突变检测。    

      多年来，Sentieon软件被业内的制药企业、科研院所、临床医学、农业基因组等领域的用户广泛采用。为了让更多用户了解Sentieon在自己工作的领域的应用案例，INSVAST从已发表的项目中精选一些有代表性文章作为案例分享给大家。

      本期通过分享5篇已发表文章来介绍Sentieon在基因诊断公司中的应用。 

 

Helix 

 

两大人群队列测序数据分析鉴定表型相关的罕见变异

 

标题：Genome-wide rare variant analysis for thousands of phenotypes in over 70,000 exomes from two cohorts

发表期刊：Nature Communications

发表日期：2020年1月28日

主要作者单位：Helix

使用Sentieon模块：A custom version

 

We analyze rare (MAF < 0.1%) variants against 4264 phenotypes in 49,960 exome-sequenced individuals from the UK Biobank and 1934 phenotypes (1821 overlapping with UK Biobank) in 21,866 members of the Healthy Nevada Project (HNP) cohort who underwent Exome + sequencing at Helix. After using our rare-variant-tailored methodology to reduce test statistic inflation, we identify 64 statistically significant gene-based associations in our meta-analysis of the two cohorts and 37 for phenotypes available in only one cohort. This comprehensive analysis illustrates the biological value of large, deeply phenotyped cohorts of unselected populations coupled with NGS data.

Centogene AG 

 

高肿瘤突变负荷，微卫星稳定，POLE单等位基因突变与高抗性结直肠癌相关

 

标题：High mutational burden in colorectal carcinomas with monoallelic POLEmutations: absence of allelic loss and gene promoter methylation

发表期刊：Modern Pathology

发表日期：2019年12月19日

主要作者单位：Centogene AG

使用Sentieon模块：Sentieon Somatic Variant Pipeline

 

Hypermutator-type colorectal carcinomas are microsatellite-stable and have point mutations of the exonuclease domain of the DNA polymerase ε or δ genes (POLE and POLD1, respectively), and an ultrahigh tumor mutational burden (TMB). These tumors may be associated with enhanced antitumor immunity and preferentially afflict younger patients. We performed POLE and POLD1 exonuclease domain Sanger sequencing of 271 unselected colorectal carcinomas. We identified two microsatellite-stable tumors with somatic POLE p.P286R variants, both with ultrahigh TMBs as demonstrated by whole exome sequencing. A POLE p.V411L was found in another two microsatellite-stable tumors with ultrahigh TMBs.

WuxiNextCode Genomics 

 

全基因组测序鉴定出食道鳞状上皮癌预后与疗效预测相关的基因通路

 

标题：Whole genome sequencing of 508 patients identified key molecular features associated with poor prognosis in esophageal squamous cell carcinoma

发表期刊：Cancer Cell

发表日期：2019年9月5日

主要作者单位：WuxiNextCode Genomics

使用Sentieon模块：Sentieon TNseq

 

Esophageal squamous cell carcinoma (ESCC) is a poor-prognosis cancer type with limited understanding of its molecular etiology. Here we sequenced 508 ESCC genomes, identified six novel significantly mutated genes including RPS15 and uncovered mutational signature clusters associated with metastasis and patients’outcome. Approximately 5.9% and 22.6% of patients had high tumor mutation burden or actionable mutations, respectively, and may benefit from immunotherapy or target therapies. Collectively, we reported the largest genomic profiling of ESCC useful for developing ESCC-specific biomarkers for diagnosis and treatment.

GRAIL Inc 

 

cfDNA含量可用来早期诊断高致死癌症

 

  • 标题：Tumor shedding into cell-free DNA (cfDNA) is associated with high-mortality Cancers

  • 发表期刊：2019 Cold Spring Harbor Laboratory Meeting: The Biology of Genomes

  • 发表日期：2019年5月7日

  • 主要作者单位：GRAIL Inc.

  • 使用Sentieon模块：Sentieon TNseq

 

Estimated cell-free DNA (cfDNA) tumor fraction (ECTF), the proportion of tumor molecules in a cfDNA sample, is a direct measurement of signal for cfDNA cancer applications. There is a need for increased understanding about the nature of ECTF and factors influencing its abundance in cfDNA. Independent of tumor sequencing, cfDNA classifiers of cancer vs non-cancer for whole-genome bisulfite (WGBS) and whole genome (WGS) (both sequenced at 30x depth) were trained on a training dataset, locked, and then applied to a test dataset. These data suggest that cfDNA-based assays may detect high mortality cancers at earlier stages due to increased cfDNA shedding among those cancer types.

Abbott Molecular, Inc.

 

胶质瘤样本中EGFR基因拷贝数异常检测：转录组和外显子测序准确度优于蛋白表达量方法

 

标题：Comparison of biomarker assays for EGFR：implications for precision medicine in patients with glioblastoma

发表期刊：Clinical Cancer Research

发表日期：2019年2月22日

主要作者单位：Abbott Molecular, Inc.

使用Sentieon模块：Sentieon BWA, Sort, Dedup, Realigner

 

We systematically evaluated methods of assessing EGFR amplification by multiple assays. Specifically, we evaluated correlation among fluorescence in situ hybridization (FISH), a standard assay for detecting EGFR amplification, with other methods. EGFR mRNA expression levels by RNA sequencing (RNAseq) and RT-PCR were highly correlated with EGFR amplification assessed by FISH. High concordance was also observed when comparing FISH to WES. RNA expression was superior to protein expression in delineating EGFR amplification. Collectively, our results provide enhanced understanding of available screening options for patients, which may help guide EGFR-targeted therapeutic approaches.

 

总结

       

      除了本文中精选的五篇发表文献之外，Sentieon在全球超过两百家商业公司与学术机构中被广泛应用。测序诊断公司在开发检测流程时，往往需要考虑准确度，可靠性，速度，成本，监管报批等多个不同因素。由于每家公司每个检测流程的样本类型，制备试剂盒，测序平台有区别，无法使用同一个标准分析流程简单套用，往往需要自己开发某些模块，针对性的搭建定制化的分析流程。Sentieon软件的功能以模块化实现，非常方便用户进行二次开发，配合用户自己开发的模块共同组成整个流程。

       Sentieon软件的所有模块均经过严格的测试，拥有非常完善的文档支持，用户在向监管部门申报时可以得到我们团队及时有力的支持，共同确保申报的成功。

       与开源软件模块相比，Sentieon可以在速度和准确度上大幅度提升整个流程的性能，为用户提升交付速度和降低计算成本打下坚实的基础。