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，可用于肿瘤与遗传病突变检测。
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。
本文通过分享5篇已发表文章来介绍Sentieon在肿瘤基因组科研项目中的应用。
香港中文大学
免疫基因表达量聚类分析揭示管腔乳腺癌的肿瘤异质性
标题：Immune gene expression profiling reveals heterogeneity in luminal breast tumors
发表期刊：Breast Cancer Research
发表日期：2019年12月19日
主要作者单位：香港中文大学
使用Sentieon模块：Sentieon TNscope
Heterogeneity of immune gene expression patterns of luminal breast cancer (BC) has not been well studied especially in non-European populations. We performed immune gene expression profiling of tumor and adjacent normal tissue in 92 luminal BC patients from Hong Kong using RNA-sequencing data and used unsupervised consensus clustering to stratify tumors. We then used luminal patients from The Cancer Genome Atlas (TCGA, N = 564) and a Korean breast cancer study (KBC, N = 112) as replication datasets. Based on the expression of 130 immune-related genes, luminal tumors were stratified into three distinct immune subtypes. The presence of three immune subtypes within luminal BC was replicated in TCGA and KBC, although the pattern was more similar in Asian populations.
全外显子测序计算肿瘤突变负荷（TMB）的方法介绍
标题：Measuring tumor mutational burden using whole-exome sequencing
发表期刊：Methods in Molecular Biology
发表日期：2019年9月10日
主要作者单位：National Institutes of Health
使用Sentieon模块：Sentieon Somatic Variant Pipeline
Cancer immunotherapy, particularly a class collectively called the immune checkpoint, is one of the most promising approaches for cancer treatment. More recently, several groups found that response to ICI therapy strongly correlates with a high burden of single nucleotide variant (SNV) mutations in the tumor genome, termed tumor mutational burden (TMB), usually expressed as the number of nonsynonymous single nucleotide variants per megabase of sequenced genome. These studies showed that TMB is a promising predictive biomarker for ICI response in melanoma, urothelial carcinoma and a subset of NSCLC patients. In this chapter I describe the current best-practice methods for measuring TMB in tumor specimens using whole-exome sequencing (WES).
基因组和转录组数据揭示三阴性乳腺癌（TNBC）的四种亚型和潜在治疗靶点
标题：Genomic and transcriptomic landscape of triple-negative breast cancers: subtypes and treatment strategies
发表期刊：Cancer Cell
发表日期：2019年3月7日
主要作者单位：复旦大学
使用Sentieon模块：Sentieon TNseq TNscope
We comprehensively analyzed clinical, genomic, and transcriptomic data of a cohort of 465 primary triple-negative breast cancer (TNBC). PIK3CA mutations and copy-number gains of chromosome 22q11 were more frequent in our Chinese cohort than in The Cancer Genome Atlas. We classified TNBCs into four transcriptome-based subtypes: (1) luminal androgen receptor (LAR), (2) immunomodulatory, (3) basal-like immune-suppressed, and (4) mesenchymal-like. Putative therapeutic targets or biomarkers were identified among each subtype. Importantly, the LAR subtype showed more ERBB2 somatic mutations, infrequent mutational signature 3 and frequent CDKN2A loss. The comprehensive profile of TNBCs provided here will serve as a reference to further advance the understanding and precision treatment of TNBC.
外显子和RNA测序在异种移植卵巢癌模型中揭示化疗抗性相关基因
标题：Genetic profiles associated with chemoresistance in patient-derived xenograft models of ovarian cancer
发表期刊：Cancer Research and Treatment
发表日期：2018年11月6日
主要作者单位：Yonsei University College of Medicine
使用Sentieon模块：Sentieon Realigner, QualCal, Haplotyper
Recurrence and chemoresistance (CR) are the leading causes of death in patients with high-grade serous carcinoma (HGSC) of the ovary. We compared gene expression and mutations between chemosensitive (CS) and CR PDX tumors with whole exome and RNA sequencing and selected candidate genes. RNA sequencing analysis of the PDX tumors revealed that 146 genes were significantly up-regulated and 54 genes down-regulated in the CR group compared with the CS group. Whole exome sequencing analysis showed 39 mutation sites were identified which only occurred in CR group. PDX-based genetic profiling study could be used to select some candidate genes that could be targeted to overcome chemoresistance of ovarian cancer.
三期临床试验结果：纳武利尤单抗一线疗法在IV期或复发性非小细胞肺癌中与化疗相比总生存期相近
标题：First-Line Nivolumab in Stage IV or Recurrent Non–Small-Cell Lung Cancer
发表期刊：The New England Journal of Medicine
发表日期：2017年6月22日
主要作者单位：The Ohio State University
使用Sentieon模块：Sentieon Somatic Variant Pipeline
In an open-label phase 3 trial, we compared first-line nivolumab with chemotherapy in patients with PD-L1–positive NSCLC. We randomly assigned, patients with untreated stage IV or recurrent NSCLC and a PD-L1 tumor-expression level of 1% or more to receive nivolumab or platinum-based chemotherapy. Among the 423 patients with a PD-L1 expression level of 5% or more, the median progression-free survival was 4.2 months with nivolumab versus 5.9 months with chemotherapy, and the median overall survival was 14.4 months versus 13.2. Nivolumab was not associated with significantly longer progression-free survival than chemotherapy among patients with previously untreated stage IV or recurrent NSCLC with a PD-L1 expression level of 5% or more. Overall survival was similar between groups.
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。
肿瘤基因组学的数据分析是一个飞速进展的领域，新的标准集和新的分析软件层出不穷。在临床科研中，研究者始终需要关心的一个问题是变异检测的准确性以及检测速度的平衡。其中的关键点就是软件是否会在indel附近对所有序列进行局部重组装，这一步可以大幅度提升indel本身以及indel附近的其他突变的检测准确率，但是代价就是会增加很多运算量，拖慢运算速度。这两类软件都有用户在使用，例如以Mutect2为代表的包含局部重组装流程的软件，以及以VarDict为代表的基于序列堆叠的软件。Sentieon的TNseq和TNscope软件很好的融合了两类软件的优点，达到了Mutect2的准确度的同时将速度提升了10倍，用户可以兼得准确度与速度。
另一方面，由于肿瘤NGS序列的复杂性，业界开始尝试利用机器学习原理训练模型去识别变异。Sentieon利用自身在机器学习领域的经验，为TNscope软件开发了可重训练的机器学习模块，可以适应用户面对的特殊样本类型或者特殊处理流程，达到远超人工调参的准确度。
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。
