Prevalence of recurrent oncogenic fusion in mismatch repair-deficient colorectal carcinoma with hypermethylated MLH1 and wild-type BRAF and KRAS. This site needs JavaScript to work properly. Tracking the quality profile can identify issues with sequencing chemistry and/or instruments. Hence, it is of utter importance to Selective Killing of SMARCA2- and SMARCA4-deficient small cell carcinoma of the ovary, hypercalcemic type cells by inhibition of EZH2: in vitro and in vivo preclinical models. Commercial test developers, laboratory leaders, and other stakeholders can use products from the site to create a suite of customizable standard operating procedures to guide use of NGS technologies and production of high-quality sequencing data. 2020;8:e000438. The previously reported V1067G mutation, which destabilizes the ARID domain, was not detected in any of the cases included in this study [67]. This is especially beneficial to laboratories that perform NGS-based tests subject to CLIA regulations and other laboratory accreditation standards. Bioinformatics 30, 3137 10.1093/bioinformatics/btt310 Ogiwara H, Takahashi K, Sasaki M, Kuroda T, Yoshida H, Watanabe R, et al. SWI/SNF-mutant cancers depend on catalytic and non-catalytic activity of EZH2. studied the airway epithelial homeostasis using NGS and genome expression microarray and discovered myocyte enhancer factor 2C (MEF2C), MAM domain containing glycosylphosphatidylinositol anchor 1 (MDGA1), and K+ voltage-gated channel subfamily J member 2 (KCNJ2) genes to have a significant role. Google Scholar. Test your website to make sure your changes were successfully saved. 4c). PubMed 2020;19:117693512092215. Synthetic lethality by targeting EZH2 methyltransferase activity in ARID1A-mutated cancers. Interseasonal differences were also observed. Specifically, ARID, which is a conserved helix-turn-helix motif-containing domain, plays a role in recruiting SWI/SNF to the target gene promoters, whereas the function of the BAF250_C domain, which contains motifs, such as NES and LXXLL-motif, that putatively mediate proteinprotein interactions, is still unknown [63]. Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists. It is more important than ever that laboratories strive to develop pipelines with the highest possible performance standards and validate them as stringently as possible to reduce errors. Bioinformatics. The Illumina technology produces the best data when all four bases are equally represented e.g. JAMA Oncol. CAS Whole-exome sequencing. Google Scholar. Synthetic lethal interactive pairs and chemical inhibitors involving SWI/SNF members. Combining gene mutation with gene expression data improves outcome prediction in myelodysplastic syndromes. Howard TP, Arnoff TE, Song MR, Giacomelli AO, Wang X, Hong AL, et al. Truncating mutations of hSNF5/INI1 in aggressive paediatric cancer. Romero OA, Vilarrubi A, Alburquerque-Bejar JJ, Gomez A, Andrades A, Trastulli D, et al. <> 2021. https://doi.org/10.1038/s41698-021-00206-y. Find out how one clinical laboratory used our reference material to generate and monitor the quality control metrics in the case studybelow. endobj Article 2014;46:4279. A second commonly used method also amplifies the sequencing template, but uses emulsion PCR to accomplish it. Quality control of next-generation sequencing data without a reference . As with any assay there are quality measures that are evaluated. 2013;31:2139. The MicroArray and Sequencing Quality Control (MAQC/SEQC) consortium helps with improving microarray and next-generation sequencing technologies and their application. The Role of Quality Control in Targeted Next-generation Sequencing Quality Scores - Illumina, Inc. Synthetic lethality occurs when a combination of deficiencies in two genes leads to cell death, whereas deficiency in only one gene results in a viable phenotype [50]. Informed and automated k-mer size selection for genome assembly. Cancer Lett Elsevier. studied the nasal microenvironment using NGS to characterize the transient and resident bacteria involved in asthma pathogenesis. In 2019, CDC and theAssociation of Public Health Laboratories(APHL) launched the Next Generation Sequencing (NGS) Quality Initiative Project. Next Generation Sequencing Next 2021. https://doi.org/10.1038/s41467-021-21893-y. J Clin Oncol. In a random fragment library from a "normal" genome you would expect to see all four bases equally represented. Similarly, we found that PBRM1 mutations were associated with a better outcome of ICI treatments than the other SWI/SNF gene mutations (Fig. The continuing decrease in massively parallel or next-generation sequencing (NGS) costs has enabled large projects consisting of hundreds or thousands of samples. This includes Whole Exome Sequencing (WES) projects with multiple samples for each individual, as well as projects with WES and 2019;10:557. The subset carrying both SWI/SNF and MLL2/3 mutations showed higher average TMB values (MLL2, 70.9 mutations/Mb; MLL3, 74.5 mutations/Mb), TMB-H ratios (MLL2, 80.5%; MLL3, 83.6%), and MSI-H ratios (MLL2, 48.6%; MLL3, 46.6%) than the whole SWI/SNF-mutant group (all p<0.0001). FastQC: per base sequence quality very good quality calls reasonable quality poor quality median blue: mean yellow: 25%, 75% whiskers: 10%, 90% 7 Basic Statistics Note: sample.fastq is 0.05% of original fastq We have to know the quality encoding to use the appropriate parameter in the mapping step. Oncol Rep Greece. 2018;17:2279. If you go to your temporary url (http://ip/~username/) and get this error, there maybe a problem with the rule set stored in an .htaccess file. 2016;34:15563. 3). Comparison and integration of deleteriousness prediction methods for nonsynonymous SNVs in whole exome sequencing studies. (c) Targeting the functions of the SWI/SNF complex. The complete sequencing of the human genome during the early 2000s192194 engendered a need for relatively inexpensive, high-throughput sequencing methods, a need that was met by several NGS platforms that were quickly commercialized. Oluwole OG, Kuivaniemi H, Abrahams S, Haylett WL, Vorster AA, Van Heerden CJ, et al. p<0.1. Cancer Res. Minimal requirements for ISO15189 validation and accreditation Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. ARID1A deficiency promotes mutability and potentiates therapeutic antitumor immunity unleashed by immune checkpoint blockade. PubMed Central Furthermore, the patient group with mutations at two or more SWI/SNF genes had significantly higher TMB values (69.0 vs. 11.3 mutations/Mb, p <0.0001), TMB-H ratios (86.2% vs. 40.5%, p <0.0001), and MSI-H ratios (48.0% vs. 5.3%, p <0.0001) than those with mutations in a single SWI/SNF gene. ARID1A deficiency impairs the DNA damage checkpoint and sensitizes cells to PARP inhibitors. Article Subunits of ARID1 serve as novel biomarkers for the sensitivity to immune checkpoint inhibitors and prognosis of advanced non-small cell lung cancer. ACMG clinical laboratory standards for next-generation sequencing. 2023-05-01 | NYSE:CRL | Press Release | Charles River SWI/SNF complex gene variations are associated with a higher tumor mutational burden and a better response to immune checkpoint inhibitor treatment: a pan-cancer analysis of next-generation sequencing data corresponding to 4591 cases. Kim KH, Roberts CWM. Proc Natl Acad Sci. A few studies have been conducted utilizing high-throughput NGS for asthma risk assessment, diagnosis, and treatment guidance. SWI/SNF complex genes are frequently mutated in a wide range of cancers and are closely associated with TMB-H, MSI-H, and superior responses to ICIs in colorectal cancer, gastric cancer, and non-small cell lung cancer. M$Oo2m{1R@EUJ#Xy8>ci3H wa#`_m>+27& jofvWfr;+j\#,tB=`\Bcy9.RL. FCW:u5=&F$G$'F&j#"K&f,x,to`JrnywHWpZ2gP &4 PBRM1 deficiency confers synthetic lethality to DNA repair inhibitors in cancer. Lee SJ, Cimica V, Ramachandra N, Zagzag D, Kalpana GV. Thus, the detection of a SMARCA4 variant via NGS was useful not only in defining the particular pathological diagnosis but also in providing important clues for the choice of treatment for SMARCA4-deficient lung cancer. European Journal of Human Genetics. The current study demonstrated SWI/SNF complex variations were tightly associated with superior ICI response in several solid tumors, such as colorectal cancer, gastric cancer, and non-small cell lung cancer, especially when combined with TMB-H status. Wilson BG, Wang X, Shen X, McKenna ES, Lemieux ME, Cho YJ, et al. Compared with no screening at all, NGS-based carrier screening would avert 223 additional affected births. 2a), possibly because the study included a very high proportion of colorectal cancer cases, and reportedly, D1850fs is an ARID1A hot spot in colorectal cancer [65]. Next-generation sequencing is a relatively new technology based on massively parallel sequencing (MPS). Schoenfeld AJ, Bandlamudi C, Lavery JA, Montecalvo J, Namakydoust A, Rizvi H, et al. 2022;71:46778. PD-1 blockade in tumors with mismatch-repair deficiency. 2021;16:117687. Identification of altered genes in gallbladder cancer as potential driver mutations for diagnostic and prognostic purposes: a computational approach. 25.2), the DNA of the sample that is being sequenced (e.g. 12 0 obj However, the systematic workflow evaluation on clinical respiratory samples and implementation of quality controls (QCs) is still lacking. When public health laboratories (PHLs) use a QMS to ensure high-quality NGS data, they can deliver more accurate and reliable test results, which can improve the health of patients and communities. Kerl K, Moreno N, Holsten T, Ahlfeld J, Mertins J, Hotfilder M, et al. WebMore and more next-generation sequencing (NGS) data are made available every day. Thus, in this study, these relationships were further analyzed. 2019;10:558. Clinical and public health laboratory (PHL) personnel can find free tools and resources to introduce or strengthen quality management in their workflows, available online from the Next Generation Sequencing (NGS) Quality Initiative. 1999;65:13428. Next-generation sequencing (NGS) is a low-cost platform for sequencing DNA using simultaneous parallel sequencing reactions for short DNA fragments. Synthetic lethal targeting of ARID1A-mutant ovarian clear cell tumors with dasatinib. These cookies allow us to count visits and traffic sources so we can measure and improve the performance of our site. SMARCA4 and other SWItch/Sucrose nonfermentable family genomic alterations in NSCLC: clinicopathologic characteristics and outcomes to immune checkpoint inhibition. Therefore NGS is playing an increasingly important role in clinical practice. Sun S, Liu Y, Eisfeld A-K, Zhen F, Jin S, Gao W, et al. Nat Cell Biol. Centers for Disease Control and Prevention. Basic local alignment search tool. Google Scholar. doi: 10.1101/cshperspect.a036798. All information these cookies collect is aggregated and therefore anonymous. Mol Cancer Ther. quality control WebThe advent of next-generation sequencing (NGS) technologies has revolutionized the world of genomic research. The properties will tell you the path and file name that cannot be found. Since its invention, next-generation sequencing (NGS) technology has shown promise in many research areas, and recently, the technology has found its way into the doi: 10.1371/journal.pone.0060234. In their paper, Kadri S and colleagues briefly discuss the standard methods used for preprocessing data and variant calling and outline in detail various other bioinformatics modules that can be incrementally added to a bioinformatics pipeline to detect emerging and more complicated biomarkers in parallel with existing workflows (Kadri, 2018). Specifications Intended Use EUA Approved Intended Use It is also possible that you have inadvertently deleted your document root or the your account may need to be recreated. Nat Protoc. [ 10 0 R] 2017;114:1224954. Kato S, Goodman A, Walavalkar V, Barkauskas DA, Sharabi A, Kurzrock R. Hyperprogressors after immunotherapy: analysis of genomic alterations associated with accelerated growth rate. Source Code Biol Med. 2019;79:240414. In this study, we observed that R1989* was captured less frequently than D1850Tfs*33 and D1850Gfs*4 (Fig. Loss of PTEN promotes resistance to T cell-mediated immunotherapy. We have used this workflow extensively to perform quality control on a variety of sequencing projects. Rampias T, Karagiannis D, Avgeris M, Polyzos A, Kokkalis A, Kanaki Z, et al. PubMed Central It was observed that lower fungal diversity of different taxonomic groups leads to an increased risk of asthma development in later life probably due to immunological priming. Our scientists have years of experience analyzing libraries and troubleshooting issues. Quality Control This Web Collection presents the results of the Sequencing Quality Control 2 (SEQC2) project that sought to evaluate quality-control metrics and human, bacterial and These documents and tools were developed based upon best available information, reviewed, edited, and approved by the participants in the group listed above. Wang Y, Chen SY, Karnezis AN, Colborne S, Dos SN, Lang JD, et al. Nat Biotechnol. Quality Assurance and Validation of Generation Sequencing 2017;16:85060. Use of these products helps ensure accurate, consistent sequencing results that conform to regulatory requirements, when applicable. Sequence quality should be high, generally above Q30, along the length of a good Illumina read. WebStep 2 in NGS Workflow: Sequencing. After sequencing and variant analysis, results need to be verified and validated using a technology other than NGS, such as Pyrosequencing. Marabelle A, Aspeslagh S, Postel-Vinay S, Soria J-C. JAK mutations as escape mechanisms to AntiPD-1 therapy. 2023-05-01 | NYSE:CRL | Press Release | Charles River Mol Cell Biol. In a study on lung cancer, the genes most frequently co-mutated with SMARCA4 were TP53 (56%), KEAP1 (41%), STK11 (39%), KRAS (36%), and EGFR (14%) [68]. The continuing decrease in massively parallel or next-generation sequencing (NGS) costs has enabled large projects consisting of hundreds or thousands of samples. Genome Sequencing and Assembly by Long Reads in Plants. Selective sensitivity of EZH2 inhibitors based on synthetic lethality in ARID1A-deficient gastric cancer. The lysine-specific methyltransferase KMT2C/MLL3 regulates DNA repair components in cancer. Previous studies have revealed the existence of a potential linkage between the SWI/SNF chromatin remodeling complex and DNA repair, TMB, and MSI [6]. Cookies used to track the effectiveness of CDC public health campaigns through clickthrough data. Rosenquist R, Cuppen E, Buettner R, Caldas C, Dreau H, Elemento O, et al. NGS QC Toolkit: a toolkit for quality control of next Cancer Genet. endobj Quality control NGS technologies produce high amounts of raw data, but they also generate artifacts and errors despite being much faster and cheaper. See this image and copyright information in PMC. Laboratory professionals can download free NGS tools from CDC's website. 2010;18:31628. Elife. This was the first whole-exome sequencing study performed for variant identification in an asthmatic family [68]. Loss of ARID1A activates mTOR signaling and SOX9 in gastric adenocarcinomarationale for targeting ARID1A deficiency. Next-generation sequencing (NGS) is getting routinely used in the diagnosis of hereditary diseases, such as human cardiomyopathies. These products serve the needs of laboratory professionals, bioinformaticians, quality managers and supervisors, laboratory managers, epidemiologists, and microbiologists who are interested in NGS data quality or have a role in quality management. Look for the .htaccess file in the list of files. Quality Control Terms and Conditions, 2018;359:7705. SWI/SNF-mutant colorectal cancer, endometrial cancer, and gastric cancer exhibited both higher TMB-H and MSI-H ratios than their SWI/SNF-non-mutant counterparts (Table 3). By continuing you agree to the use of cookies. Before Here we show that by generating a rapid, non-optimized draft assembly of raw reads, it is possible to obtain reliable and informative QC metrics, thus removing the need for a high quality reference. Association for Clinical Genetic Science. Pharmaceuticals. Additionally, the DUF3518 domain of ARID1A was found to be functionally necessary to antagonize EZH2, and both the R1989* variant and the deletion of the DUF3518 domain could not rescue EZH2-mediated IFN- signaling gene repression in ARID1A-knockout ovarian cancer cells [66]. PubMed The mammalian SWI/SNF chromatin remodeling complex plays a crucial role in cellular and tissue development, and SWI/SNF subunits have been implicated as suppressors in a variety of human cancers [7, 62]. If your blog is showing the wrong domain name in links, redirecting to another site, or is missing images and style, these are all usually related to the same problem: you have the wrong domain name configured in your WordPress blog. Nat Genet. This includes publishing more training products and supporting laboratories already using our resources. Clinical utility of whole-genome sequencing in precision oncology. Given that most SWI/SNF mutations were dispersed along the full length of each gene, NGS showed potential as the most suitable strategy for detecting SWI/SNF alterations. Chabanon RM, Morel D, Eychenne T, Colmet-Daage L, Bajrami I, Dorvault N, et al. ARID1A-mutated ovarian cancers depend on HDAC6 activity. Science. J Clin Invest. WebAs a quality feature, an internal control consisting of 11 human mRNA targets is included in every sample. Careers. Correspondence to Cancer Discov United States. WebLearn about the Next Generation Sequencing (NGS) platform through our collection of free resources, including an introduction into the theory, comparisons between different NGS technologies, experimental design (coverage, library preparation, and quality control), data analysis (raw data, software and tools), whole genome sequencing, and more. stream A hybrid captured-based NGS assay covering approximately 1.1 megabases (Mb) of the genomic sequences of 1021 cancer-related genes (GenePlus-Beijing, China) was used for the sequencing, which was performed using a GenePlus 2000 sequencing system (Beijing, China) with 2 100 bp paired-end reads. Kang E, Tessier-Cloutier B, Duggan MA, Stewart CJR, Lee C, Kbel M. Loss of ARID1B and SMARCB1 expression are specific for the diagnosis of dedifferentiated/undifferentiated carcinoma in tumours of the upper gynaecological tract and cervix. Thus, the inhibition of EZH2 using tazemetostat or GSK126 causes synthetic lethality in ARID1A-, SMARCA4-, SMARCB1-, PBRM1-deficient cancers [49,50,51,52,53,54]. WebFor next-generation sequencing. NGS of whole exome was performed on all members (total six) of a family segregating asthma. However, the systematic workflow evaluation on clinical respiratory samples and implementation of quality controls (QCs) is still lacking. Google Scholar. In MPS (Fig. How to find the correct spelling and folder, 404 Errors After Clicking WordPress Links, From the left-hand navigation menu in WordPress, click. The use of clinical and NGS data was approved by the Ethics Committee of the Sun Yat-Sen University Cancer Center (Approval number B2020-344-01). However, this deletion is quite rare with a frequency of only 0.6% in the Hutterite family studied. Detected viruses were then genetically characterized via next generation sequencing considering that only a few phylogenetic studies have been based on the WGS of WNV (13, 15, 16). Uncovering the dosage-dependent roles of Arid1a in gastric tumorigenesis for combinatorial drug therapy. Before you do anything, it is suggested that you backup your website so that you can revert back to a previous version if something goes wrong. Recently introduced high throughput and benchtop instruments offer fully automated sequencing runs at a lower cost per base and faster assay times. Privacy /index.php [L] We all know how vital quality control (QC) is for our samples. This allows the implementation of carrier screening across a wider range of ethnically diverse populations, more closely approximating the term universal. Thank you for taking the time to confirm your preferences. 2014 May 3;9:8. doi: 10.1186/1751-0473-9-8. Cancers. NPJ Breast Cancer. 2019;8: e44161. The .gov means its official. next generation sequencing Nat Med. 2013. PubMed Step 2: Target enrichment and library preparation, After purification, nucleic acids must be processed through the NGS library preparation workflow in order to be able to meet the platform requirements with respect to size, purity, concentration and efficient ligation of adaptors (refer to the. Nie Z, Xue Y, Yang D, Zhou S, Deroo BJ, Archer TK, et al. 2018;13:126. WebNext-generation sequencing (NGS) technologies have dramatically expanded the breadth of genomics. Our results indicate that the average TMB value corresponding to SWI/SNF-mutant tumors was markedly higher than that corresponding to SWI/SNF-non-mutant tumors, regardless of the cancer type (25.8 vs. 5.6 mutations/Mb, p <0.0001). that loss of the SWI/SNF complex cannot be used as a pan-cancer biomarker of clinical benefits from ICIs. All NGS sequencing reactions are given a quality score (Q score) and the number of reads (the number of times a target is sequenced) is evaluated. 2013;8(4):e60234. Gut England. <> WILMINGTON, Mass., May 01, 2023--Charles River launches Accugenix NGS for bacterial identification and fungal ID; announces partner lab initiative to expand global The NGS Quality Initiative promotes implementation of quality management based on the CLSI quality framework for laboratories. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. SWI/SNF complex gene variations are associated with a higher tumor mutational burden and a better response to immune checkpoint inhibitor treatment: a pan-cancer analysis of next-generation sequencing data corresponding to 4591 cases, https://doi.org/10.1186/s12935-022-02757-x, http://www.openbioinformatics.org/annovar/, http://www.cbioportal.org/mutation_mapper, https://doi.org/10.1038/s41698-021-00206-y, https://doi.org/10.1016/j.semcancer.2021.06.018, https://doi.org/10.1186/s12881-020-0953-1, https://doi.org/10.1038/s41467-021-21893-y, http://creativecommons.org/licenses/by/4.0/, http://creativecommons.org/publicdomain/zero/1.0/. NGS QC Toolkit is a Perl-based stand-alone program package for the quality control (QC) of next-generation sequencing (NGS) data. Wang F, Zhao Q, Wang Y-N, Jin Y, He M-M, Liu Z-X, et al. Fig. 2021;34:222941. In the present study, NGS data corresponding to 4591 solid tumors, covering 18 types of malignancies, were retrospectively integrated to depict the spectrum of SWI/SNF variations. J. Mol. Defining guidelines and sharing best practice help guide researchers new to NGS and ensure the quality and relevance of the NGS results when shared. 2021;11:156281. Comprehensive characterization of distinct genetic alterations in metastatic breast cancer across various metastatic sites. sequencing A lot of research has gone into developing useful QC metrics for genomics experiments - primarily due to their high cost. Our products complement existing resources and support the development of a laboratorys current QMS or can act as a foundational quality system. For example, the Illumina service lab promises whole-genome sequencing with an average depth of 30 across 98% of the genome. QC procedures tracking success of library preparation steps ensure that only samples of good quality are processed downstream and sequenced to generate reads of highest quality that can be confidently turned into insights. -. Find out more about QC checks in other laboratory workflows: NGS comes with many challenges that scientists must address. Li J, Lupat R, Amarasinghe KC, Thompson ER, Doyle MA, Ryland GL, et al. There are two common methods of template selection: amplicon based or capture based.61,62 Amplicon-based target selection uses multiplex PCR reactions to amplify the sequences of interest, whereas capture-based target selection first uses baits to hybridize and capture the targets of interest, followed by PCR amplification. Am J Surg Pathol. 2021;218:e20200219. J Clin Oncol. ScienceDirect is a registered trademark of Elsevier B.V. ScienceDirect is a registered trademark of Elsevier B.V. Memorial Sloan-Kettering Cancer Center, New York, United States, David Geffen School of Medicine at UCLA, Los Angeles, United States, Kazusa DNA Research Institutes, Kisarazu, Japan, Accurate Results in the Clinical Laboratory (Second Edition), Pathology, Biomarkers, and Molecular Diagnostics, Abeloff's Clinical Oncology (Sixth Edition), Genetics, molecular biomarkers, and artificial intelligence to improve diagnostic and prognostic efficacy, Principles of Translational Science in Medicine (Third Edition), Genetics of Cardiovascular Disease and Applications of Genetic Testing, High-Throughput Methods in Molecular Pathology, Molecular and genomic basis of bronchial asthma, Advances in Molecular Genetics Including Fetal Sequencing. Caiyun He or Fang Wang. 2019;129:75973. Cancer Inform. The formalin-fixed paraffin-embedded tissue QC Kit enables assessment of the integrity of DNA. In a typical NGS workflow, experimental errors can be introduced in all steps prior to sequencing, including sample processing, DNA isolation, and polymerase chain reaction (PCR) amplification (Chen et al., 2017). Front Immunol. EMBO Rep. 2019;20:120. Zhang Y, Chang L, Yang Y, Fang W, Guan Y, Wu A, et al. ARID1A mutation sensitizes most ovarian clear cell carcinomas to BET inhibitors. Therefore, SWI/SNF-deficient cancers are vulnerable to the inhibition of homologous recombination repair factor, PARP1 [20, 49], cell cycle regulator, cyclin-dependent kinase (CDK)4/CDK6 [28, 56], DNA replication checkpoint factor, ATR [57], chromosomal segregation factor, Aurora kinase A [58], and oxidative phosphorylation [59] and glutathione [60] pathways. Notably, MLL2 (MLL4/KMT2D) and MLL3 (KMT2C), belonging to a family of mammalian histone H3 lysine 4 (H3K4) methyltransferases [45], were frequently co-mutated with SWI/SNF genes (Fig. RewriteCond %{REQUEST_FILENAME} !-f A major chromatin regulator determines resistance of tumor cells to T cellmediated killing. Okamura R, Kato S, Lee S, Jimenez RE, Sicklick JK, Kurzrock R. ARID1A alterations function as a biomarker for longer progression-free survival after anti-PD-1/PD-L1 immunotherapy. Genomic correlates of response to immune checkpoint therapies in clear cell renal cell carcinoma. Huang DW, Sherman BT, Lempicki RA. There are also RNA-based panels for the detection of fusion genes resulting from translocations. 2019;30:4456. Most of these variants were located in three asthma candidate genes, that is, PDE4DIP, CBLB, and KALRN. Cancer Res. Saito M, Kono K. Landscape of EBV-positive gastric cancer. 2023 Apr 18;14(1):2214. doi: 10.1038/s41467-023-37696-2. In the context of genomics and molecular pathology, computational, mathematical, and statistical tools are used to collect, organize, and analyze large and complex genetic sequencing data and related biological data.