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Get Ready for the Future of Gene Variant Interpretation with Molecular Health Guide

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Get Ready for the Future of Gene Variant Interpretation with Molecular Health Guide For molecular pathologists 28,000 gene variant-drug relations. Get ready for the future of gene variant interpretation with Molecular Health Guide With MH Guide you get full access to the global clinical knowledge data platform Dataome, with today over 28,000 gene variant-drug relations. About MH Guide Dataome, the backbone of MH Guide MH Guide is an automated clinical interpretation software that accepts any variant list in VCF file format. These files contain structured information regarding the beginning and end Dataome, a global clinical knowledge data platform, is based on positions of the genetic variant, a measure for the observation quality, the variant type, and large biomedical and drug data sets combined with novel artificial copy number changes, total read count, and reference and alternate allele frequencies. intelligence and machine learning (AI/ML) technologies. It provides unparalleled evidence by connecting real-world patient outcome With MH Guide Premium, MH Guide can be expanded with a bioinformatic pipeline that data to up-to-date state of clinical and molecular knowledge. accepts raw sequencing data (FASTQ files) or aligned sequencing data (BAM files). MH Guide also supports output from non-NGS methods such as FISH, IHC, (q)PCR, and microarrays. Data that is not compatible with VCF format can be added manually (e.g. protein expression data). 28,000 curated gene Regardless of the origin of the VCF file, the MH Guide automated analysis interprets the variant drug relations patient’s genetic variants using data derived from the global clinical knowledge data platform, Dataome, containing up-to-date published scientific and biomedical evidence on cancer treatments, pathways, genes, variants, and clinical trials. Quality assurance by curation of data Scientific peer-reviewed literature Automated/assisted tools Scientifically relevant (TDM, TREX) Clinical Scientific curation of relevant content Medical review of relevant content Clinically and contextually relevant information Molecular Health provides quality assurance by curation of data – a sophisticated process, in which the data is regularly updated and finally curated by medical and scientific experts. Our regular updates of MH Guide assure that information about new biomarkers and approved drugs is implemented quickly so that you get the information you need. Dataome is the ultimate data source for MH Guide From NGS data to treatment options: Clinical Variant Interpretation (CVI) MH Guide analyzes NGS data from commercial or customized panels, and WES to identify and interpret relevant gene variants detected in the patientʼs tumor. We call this clinical variant interpretation. Patient ID — Diagnosis Lung adenocarcinoma Case ID — ICD-10-CM code — Date of birth — MeSH ID/term — Additional MeSH IDs — Impact Sex Male Primary tumor site — Collected — Ordering — Ethnicity — Surgical pathology — Tumor cellularity — physician Country US issue type — arcode — Facility — — — — Email — • Predictive Trial ZIP Metastatic Sample type Unstructured code Phone — General dataset ID — Labtest — Fa — CVI dataset ID — Product MH Guide Organizational unit — — (effective, — Variants data without Report Mutational status of commonly mutated genes in the patient disease • Gene name ineffective, AC1 ALK BRAF EGF E2 KRAS ME NF1 NRAS PIK3CA related evidence not fusion, not not not not not not not not identified SNV identified identified identified identified identified identified identified identified • Variant name safety) SK11 P53 OS1 not not del identified identified (HGVS) • Diagnostic SUMMARY • Somatic or • Prognostic verview of potential treatment impacts verview of prognostic and diagnostic findings 3 2 1 Safety 0 Prognostic 0 Diagnostic germline Potential impact Treatment Drug approval* iomarker VAF iomarker score • Zygosity ALEML Lorlatinib Approved — Biomarker score (fusion) ALEML Structured dataCeritinib relatedApproved to— (fusion) • CVI score: ALEML rigatinib Approved — clinical evidence, curated(fusion) by preclinical GD pH Diseases Safety Dabrafenib Approved 99.56% (SNV) (1-3), clinical AL pLM scientific and Crimedicalzotinib Approved experts23.80% List of diseases (SNV) AL pLM (4-6), clinically Alectinib Approved 23.80% (SNV) related to the in the patient's disease VAF Variant allele freuency Biomarker score: AMP score and CVI score Clinically approved: approved (7) disease Clinical: variant drug Preclinical: translational data You can find more details on the biomarker score (AM and CVI score) in the glossary. • AMP score Treatments Order date Nov Signed by Phone — Narrative Report Version 5 Dec : (TC:) Dataome integrates data from various data resources: Molecular Health GmbH, KurfuerstenAnlage , Heidelberg wwwmolecularhealth.com • List of Summary of the treatments CVI • For variant identification and biomarker annotation: ACMG variant classification1, • CVI score and COSMIC2, BRCA Exchange3, CVIs (proprietary of Molecular Health), AMP/CAP/ASCO AMP score classification4, GNOMAD based population frequencies5, and others References List of • For recommendation of drugs and clinical trials: WHO and NCT clinical trials, Drug Dev publications Stages (Global), NCCN guidelines, curated ESMO guidelines, Clinical Trial NGS Biomarker, and their corresponding and others PubMed IDs Dataome contains structured data that were integrated using ETL (extract, transform, load) processes, and data from unstructured sources (free text). Each CVI is based on published biomedical knowledge. Each CVI lists the relevant information regarding the variant, lineage (germline or somatic), Interested in becoming a disease association, treatment (drug or drug combination), treatment impact (effective, curation expert for MH Guide? ineffective, toxic), prognostic or diagnostic biomarkers, biomarker validity (preclinical, Let us know! clinical, clinically approved), and a narrative summarizing the clinical knowledge available ? for the variant. If relevant, information on developmental stage of the drug(s) and potentially recruiting clinical trials is added. Any conflicting evidence is also reported. Standard output formats are PDF, JSON and XML. An adapter is available to adapt the output to other formats, if required. From NGS data to MH Guide report You can use MH Guide default or customized filters and rule sets according to your needs 1. Variant filter • Define variants to be considered for report 2. Lineage and zygosity • Classify variants according to lineage and zygosity NGS data from Clinical variant Identified • Filter out germline variants with no matching CVI tumor sample interpretation biomarkers Variant identification Filters 3. CVI match quality passed – variant is Report summarizes and • Define matching parameters included in Patient ID — Diagnosis Lung adenocarcinoma Case ID — ICD-10-CM code — classifies identified treatment Date of birth — MeSH ID/term — between variants and CVIs the analysis Additional MeSH IDs — • SNVs • TMB Sex Male Primary tumor site — Collected — Ordering — options, as well as prognostic Ethnicity — Surgical pathology — Tumor cellularity — physician Country US Tissue type — Barcode — Facility — Trial ZIP — Metastatic — Sample type — Email — • Indels • Gene code Phone — General dataset ID — Labtest — Fax — CVI dataset ID — Product MH Guideand diagnostic variants relevant a c Software version — Organizational unit — — MH Guide report Report • Fusions expression Filters Mutational status of commonly mutated genes in the patient disease b 4. TMB calculation ABCB1 ALK BRAF EGFR ERBB2 KRAS MET NF1 NRAS PIK3CA forRET treatment by a traffic-light failed – not 1 fusion, 1 not not not not not not not not not • CNAs • Protein identified SNV identified identified identified identified identified identified identified identified identified STK11 TP53 ROS1 b c not not 1 del identified identified color code as potentially • MSI expression variant is c SUMMARY effective, ineffective, or with • Methylation • Define counting methods for TMB excluded from Overview of potential treatment impacts Overview of prognostic and diagnostic findings Clinical trials found 3 Effective 2 Ineffective 1 Safety 0 Prognostic 0 Diagnostic 8 Trials calculation the analysis Potential impact Treatment Drug approval* Biomarker VAF Biomarker score potentialTrials safety issue. ALK/EML4 Effective Lorlatinib Approved — 2 (fusion) • Set thresholds for low and high TMB ALK/EML4 Effective Ceritinib Approved — 3 (fusion) ALK/EML4 Effective Brigatinib Approved — 5 (fusion) G6PD p.R285H Safety Dabrafenib Approved 99.56% — Identified therapeutic (SNV) ALK p.L1196M Ineffective Crizotinib Approved 23.80% — (SNV) 1) ALK p.L1196M Ineffective Alectinib Approved 23.80% — options and clinical (SNV) * in the patient's disease; VAF = Variant allele frequency 2) 5. Prioritization settings Biomarker score: AMP score and CVI score. Clinically approved: Approved biomarker (by the FDA, EMA, or NCCN) to predict a specific effect in the patient's disease. Clinical: Not yet approved biomarker for the patient's disease. Observed in clinical studies as a potential biomarker to predict a specific effect of the drug. Preclinical: This biomarker has not yet been observed/tested in patients to predict a specific effect of the drug. It is supported by preclinical evidence or translational data. 3) studies You can find more details on the biomarker score (AMP and CVI score) in the glossary. • Define sort order of treatments Order date 14 Nov 2019 Signed by Phone — Report Version 5 11 Dec 2019 12:20 (UTC+01:00)
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