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。
本文通过分享5篇已发表文章来介绍Sentieon在临床实践中发挥的作用。
北京医院
CHEK2基因突变与家族遗传性乳头状甲状腺癌表现出相关性
标题：A germline CHEK2 mutation in a family with papillary thyroid cance
发表期刊：Thyroid
发表日期：2020年3月11日
主要作者单位：北京医院、中国医学科学院
使用Sentieon模块：Sentieon Germline Variant Pipeline
We performed whole genome sequencing (WGS) of peripheral-blood DNA samples from two affected family members with PTC. CHEK2 transcript expression and the protein levels of CHK2 and p53 were evaluated in the thyroid tissues from two affected members of the kindred and sporadic PTC cases. We identified a novel heterozygous germline mutation in CHEK2 (c.417C→A) that was detected in all available affected members of a kindred with FPTC. The CHEK2 c.417C→A variant introduces a premature termination codon (Y139X). The Y139X loss-of-function variant led to reduced p53 phosphorylation and decreased p53 protein level. Our findings suggest that the CHEK2 Y139X variant may be associated with FPTC.
病例报告：NGS技术确诊遗传性球形红细胞症(HS)并Dubin-Johnson综合症
标题：Next generation sequencing reveals co-existence of hereditary spherocytosis and Dubin-Johnson syndrome in a Chinese girl: a case report
发表期刊：World Journal of Clinical Cases
发表日期：2019年10月26日
主要作者单位：中国医学科学院血液病医院
使用Sentieon模块：Sentieon Germline Variant Pipeline
Hereditary spherocytosis (HS) is a hereditary disease of hemolytic anemia that occurs due to the erythrocyte membrane defects. Dubin–Johnson syndrome (DJS), which commonly results in jaundice, is a benign hereditary disorder of bilirubin clearance that occurs only rarely. The co-occurrence of HS and DJS is extremely rare. A 21-year-old female patient presented to our department because of severe jaundice, severe splenomegaly, and mild anemia since birth. We eventually confirmed the diagnosis of co-occurring DJS and HS by next generation sequencing (NGS). The treatment of ursodeoxycholic acid in combination with phenobarbital successfully increased hemoglobin and reduced total bilirubin and direct bilirubin.
全外显子测序确认SAMD9以及SLC19A2双基因突变致产生多种症状
标题：Mutations in both SAMD9 and SLC19A2 genes caused complex phenotypes characterized by recurrent infection, dysphagia and profound deafness – a case report for dual diagnosis
发表期刊：BMC Pediatrics
发表日期：2019年10月21日
主要作者单位：广东省妇幼保健院
使用Sentieon模块：Sentieon Germline Variant Pipeline
Due to the extremely low incidence for a single disease, phenotype spectrum needs to be expanded. Meanwhile, earlier knowledge says patients who suffered from two kinds of different Mendelian disease are very rare. We describe a case of neonatal male with genital anomalies, growth delay, skin hyperpigmentation, chronic lung disease with recurrent infection, anemia, and severe deafness. Without any clear etiology after routine workflow, whole exome sequencing was carried on. A pathogenic de novo SAMD9 mutation and compound heterozygous likely-pathogenic variants in SLC19A2 were identified. Combining the phenotype and clinical progress of treatment, we report that it is the first case of a patient with both MIRAGE syndrome and TRMA syndrome.
单亲二倍体遗传(UPD)的MMAA基因致病突变导致甲基丙二酸血症
标题：Segmental uniparental disomy of chromosome 4 in a patient with methylmalonic acidemia
发表期刊：Molecular Genetics & Genomic Medicine
发表日期：2019年12月2日
主要作者单位：中山大学附属第六医院
使用Sentieon模块：Sentieon Germline Variant Pipeline
Methylmalonic acidemia (MMA) is an autosomal recessive genetic disorder involving the meta-bolism of organic acids. Here, we report the case of a patient who developed acute meta-bolic crisis after vaccination and was diagnosed with cblA type MMA after hospitalization. Using chromosomal microarray analysis, maternal uniparental disomy (UPD) was found on chrom-osome 4q26-q35.2 of the patient. The MMAA gene of the patient was inherited only from the mother and carried the same pathogenic variant on both alleles of chromosome 4. The nonsense pathogenic variant, NM_172250.2:c.742C>T (p.Gln248*), carried by the patient leads to a premature termination of transcription of the gene, thereby resulting in partial loss of protein function while retaining some others.
全外显子测序帮助确诊胚胎患有SGBS1综合症
标题：Whole exome sequencing aids the diagnosis of Simpson-Golabi-Behmel syndrome in two male fetuses
发表期刊：International Medical Research
发表日期：2019年7月15日
主要作者单位：苏州市立医院
使用Sentieon模块：Sentieon Germline Variant Pipeline
Prenatal ultrasound scans of two fetuses showed multiple congenital anomalies and hydramnios. Subsequent to termination of the pregnancies, a novel nonsense variant (c.892G>T, p.E298*) in the glypican 3 (GPC3) gene of the two fetuses was identified by WES and further confirmed by Sanger sequencing. The two fetuses were diagnosed with SGBS1. The mother was heterozygous for the c.892G>T variant. This study describes the prenatal sonographic features of SGBS1, emphasizes the role of WES in the diagnosis of SGBS1 and expands the known mutation spectrum of the GPC3 gene.
除了本文中精选的五篇发表文献之外，Sentieon在全球超过两百家医院，商业公司与学术机构中被广泛应用。在医院的临床实践中，速度与可靠性是院内诊断需要首要考虑的。例如，在新生儿急性重症诊断中，从样本采集到诊断报告的全流程耗时被压缩在了两天以内，留给全基因组二级分析的时间不会超过2个小时。在这样的情况下，快速可靠的软件成为了一个必要的选择。
另外，很多医院搭建数据分析软硬件的时候是科室采购，以相对独立的分析一体机形式存在。和全院级别的大型集群相比，一体机的算力相对偏小，尤其需要高速的分析软件来提升整体分析通量。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，为科室级别的检测赋能，使之可以达到传统大型集群的分析通量。
最后需要说明的是，Sentieon软件作为数据分析软件，不涉及到数据的存储以及传输流程，可在断网环境下本地化部署，完全符合各国对于本国遗传资源保护的相关条例。
