How expert-curated cancer data from COSMIC and HSMD can help biopharmaceutical researchers identify and validate targets faster and optimize clinical trial design.
In cancer drug discovery and development, data is king. From identifying potential molecular targets to helping predict drug toxicity and optimizing clinical trial design, high-quality data can significantly improve the efficiency and success rate of bringing new cancer therapies to market.
The Catalogue Of Somatic Mutations In Cancer (COSMIC) and the Human Somatic Mutation Database (HSMD) are two expert-curated somatic databases exclusively licensed through QIAGEN that enable biopharmaceutical researchers to avoid pitfalls in early cancer drug discovery, confidently qualify candidate drug targets, and accelerate indication expansion and repurposing of existing cancer therapies.
In this blog, we take a closer look at COSMIC and HSMD for biopharmaceutical research, providing an overview of the expert curation processes, what types of data can be found in each database, and examples of how this data can be applied through the cancer drug discovery and development pipeline.
COSMIC is an expert-curated knowledge base providing data on somatic variants in cancer, supported by a comprehensive suite of tools for interpreting genomic data, discerning the impact of somatic alterations on disease, and facilitating translational research. The catalogue is accessed and used by thousands of cancer and biopharmaceutical researchers and clinicians daily, allowing them to quickly access information from an immense pool of data curated from over 29 thousand scientific publications and large studies.
COSMIC integrates somatic data from multiple sources published around the world and allows researchers to access and scrutinize information about somatic mutations and their impact in cancer. Over the past two decades, COSMIC has been diligently collecting, cleaning, and organizing genomic data and associated metadata from cancer studies published in scientific literature and various bioinformatics sources. This data is then translated into a standardized format, integrated, and made available to the research community through well-structured datasets and user-friendly data exploration websites and tools.
In addition to the main catalogue of somatic mutations, a further 6 accompanying resources focus on different aspects of oncology (Figure 1). The Cancer Gene Census (CGC) and Cancer Mutation Census (CMC) provide additional annotations regarding the roles of genes and mutations in oncogenesis, which are based on a defined set of rules and sufficient evidence obtained through dedicated literature curation and analysis of the content of the core catalogue.
→ View the complete database numbers in the latest COSMIC v99 (December 2023) here.
Figure 1. COSMIC’s 7 key resources for understanding cancer and improving cancer patient care. The main catalogue of somatic mutations is supported by further six resources that together lay additional layers of knowledge helping to interpret the impact of somatic mutations on cancer development and presenting available therapeutic options (graphic from Sondka et al. 2024).
COSMIC’s workflows to manually curate cancer genetic data have been built to deliver high-quality, biologically and clinically-relevant data to the research community. Different data sources and types of curated data require different approaches (Figure 2). However, in each case there are common core elements.
Figure 2. COSMIC data curation flowchart. Depending on the data source and curation objectives, there are three main curation paths in COSMIC (graphic from Sondka et al. 2024).
HSMD is a web-based application that allows biopharmaceutical researchers and clinical NGS testing labs to harness genetic insights from QIAGEN’s real-world oncology dataset combined with knowledge from two decades of expert curation.
In the latest version of HSMD, the resource focuses on providing deep insight into small variants, such as SNVs, indels, frameshifts, fusions and copy number variants that have been clinically observed or curated from scientific literature to help users better understand and define precise function and actionability. This expert-curated resource contains content from over 547,000 real-world clinical oncology cases combined with content from the QIAGEN Knowledge Base (QKB), providing gene-level, alteration-level, and disease-level information.
HSMD enables users to easily search and explore mutational characteristics across genes, synthesize key findings from drug labels, clinical trials, and professional guidelines, and receive detailed annotations for each observed variant (Figure 3).
Figure 3. HSMD home screen. HSMD enables users to search by gene, alteration, disease, drugs, and clinical trials.
HSMD leverages variant content from two sources: expert-curated content from the QIAGEN Knowledge Base (QKB) and data from real-world oncology cases sourced from our professional clinical interpretation services (Figure 4).
When a variant has been “clinically observed,” it means our professional clinical interpretation service has encountered this alteration in a real-world clinical case. For these variants, QIAGEN's team has assessed the clinical and biological relevance and calculated the gene and variant prevalence across observed tumor types. Conversely, content from the QKB is proactively curated from scientific literature; therefore, not all variants have yet been directly clinically observed by our professional clinical interpretation services.
Figure 4. HSMD curation workflow. HSMD contains content from the QKB, which pulls information from all public and proprietary databases, clinical articles for the most relevant cancer genes, and thousands of clinical articles for somatic genes. Curation then occurs by artificial intelligence (AI) approaches, manual curation, or a combination of both. All content then goes through rigorous quality control to ensure consistency, accuracy, and reproducibility. In addition, HSMD contains content from over 500,000 somatic mutations submitted to QIAGEN's professional variant interpretation service, QCI Precision Insights (formerly N-of-One). This is de-identified patient data that provides even greater insight into real-world clinical cases.
COSMIC and HSMD are two expert-curated databases licensed exclusively through QIAGEN that enable biopharmaceutical companies to improve the drug discovery process, develop more effective clinical trials, and enhance the treatment of rare cancers. To learn more about how your research team can use COSMIC and HSMD, visit our product webpage or click the button below for a free trial and personal consultation with our biopharmaceutical research experts.
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Two expert-curated databases exclusively licensed through QIAGEN link sequence-level somatic mutation data to detailed molecular information about functional and clinical impacts, as well as implications for druggability and relevant clinical trials. The two databases, the Catalogue Of Somatic Mutations In Cancer (COSMIC) and the Human Somatic Mutation Database (HSMD), enable biopharmaceutical researchers to avoid pitfalls in early cancer drug discovery and development, confidently qualify candidate drug targets, and accelerate indication expansion and repurposing of existing cancer therapies.
In this blog, learn more about the high-level applications of using COSMIC and HSMD in cancer drug discovery and development pipelines.
The Catalogue Of Somatic Mutations In Cancer (COSMIC) is the most detailed and comprehensive resource for exploring the effect of somatic mutations in human cancer. Developed and maintained by Wellcome Sanger Institute, the latest release, COSMIC v99 (December 2023), includes over 6 million coding mutations across 1.5 million tumor samples, curated from over 29,000 publications. In addition to coding mutations, COSMIC covers all the genetic mechanisms by which somatic mutations promote cancer, including non-coding mutations, gene fusions, copy-number variants and drug-resistance mutations.
COSMIC integrates somatic data from multiple sources published around the world and allows researchers to access and scrutinize information about somatic mutations and their impact in cancer. Over the past two decades, COSMIC, through predominantly manual curation workflows, has been diligently collecting, cleaning, and organizing genomic data and associated metadata from cancer studies published in scientific literature and various bioinformatics sources. This data is then translated into a standardized format, integrated, and made available to the research community through well-structured datasets and user-friendly data exploration websites and tools.
The Human Somatic Mutation Database (HSMD) is a relatively new somatic mutation database from QIAGEN (released in 2019) that combines over two decades of expert curation and data from scientific literature, on- and off-label therapies and clinical trials, and real-world clinical oncology cases. In the latest release, HSMD 3.0 (November 2023), the database contains manually curated, detailed molecular information on over 1.8 million somatic variants, with more than 430,000 observed in real clinical cases, as well as data from over 545,000 real-world clinical oncology cases.
Unique to HSMD is the availability of data from clinically observed variants. When a variant has been “clinically observed,” it means QIAGEN’s professional clinical interpretation service (previously N-of-One) has encountered this alteration in a real-world clinical case. For these variants, QIAGEN assesses the clinical and biological relevance and calculates the gene and variant prevalence across observed tumor types.
Easy to search with new content added weekly, HSMD enables researchers to explore key genes or mutations with driving properties or clinical relevance and search for associated treatment options, off-label therapies, resistance markers, and regional and/or disease-specific clinical trials.
While similar, COSMIC and HSMD differ in their applications for cancer drug discovery and development. As a result, biopharmaceutical researchers can use both databases to support different workflow stages.
COSMIC is a valuable resource for cancer researchers and drug discovery efforts. Here are several ways in which the COSMIC database can be used to support exploratory research in cancer drug discovery:
HSMD is a valuable resource for biopharmaceutical researchers, facilitating the confident evaluation of cancer-related genetic variations by granting access to real-world data. Here are several ways in which HSMD supports cancer drug clinical development and post-market research.
COSMIC and HSMD are two expert-curated databases licensed exclusively through QIAGEN that enable biopharmaceutical companies to improve the drug discovery process, develop more effective clinical trials, and enhance the treatment of rare cancers. To learn more about how your research team can use COSMIC and HSMD, visit our product webpage or click the button below for a free trial and personal consultation with our biopharmaceutical research experts.
COSMIC & HSMD FOR BIOPHARMA
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When it comes to NGS variant interpretation, content is king. But when your lab’s genomics software platform relies largely on data-sharing and crowdsourced information, how reliable are your reports?
Commercial genomics software platforms support molecular diagnostic workflows by providing unified interfaces connected to selected knowledge bases. These variant interpretation tools take a list of variants and return aggregated information retrieved from individual knowledge bases. This content is then used to filter and prioritize variants and ultimately derive a diagnosis and/or treatment recommendation. Therefore, a lab’s ability to accurately interpret a variant’s biological and clinical significance lies in the strength of its genomics software platform's knowledge base.
In recent years, crowdsourcing has become increasingly prominent as a means of supplementing the data obtained from more traditional sources, such as academic papers and drug labels. Around the world, initiatives and working groups, such as ClinVar, have developed centralized resources where users can submit variants reported in patient samples and assess their significance. Even commercial software companies, such as Sophia Genetics, have created “global data-sharing networks,” enabling their users to upload and share data with other users in the network.
While crowdsourcing is beneficial when it comes to solving challenging cases, there is one inherent issue: crowdsourced data lacks standardization. Clinical laboratories and medical institutions generate patients’ genetic variants through different sequencing protocols and NGS pipelines. This leads to genetic variants that are not interoperable. As a result, data contained in crowdsourced resources is not as reliable as data contained in a standardized, exert-curated knowledge base.
But there is an inherent dilemma: For many molecular diagnostic labs, purchasing a new variant interpretation platform is not option. The question then becomes, how can molecular diagnostic labs fill in the gaps of their crowdsourced data to ensure their variant interpretation is accurate and timely.
QIAGEN Digital Insights offers two proprietary databases that can supplement your lab’s current variant interpretation platform with trusted, expert-curated content.
HGMD Professional remains the largest, manually curated resource for finding disease-causing mutations. Founded and maintained by the Institute of Medical Genetics at Cardiff University, the database attempts to collate all known (published) gene lesions responsible for human inherited disease, giving you the best possible chance of reaching a diagnosis.
Unlike other competitors who offer little to no data curation or overload users with unhelpful literature and volumes of conflicting data, HGMD Professional combines electronic and human search procedures during data curation in order to provide high-quality information. For more than 30 years, a team of expert curators has consistently screened peer-reviewed biomedical literature in over 250 journals to update HGMD Professional.
A research team at Cardiff University updates HGMD Professional quarterly. As of November 2022, HGMD Professional contains over 377,510 detailed mutation reports and more than 11,500 expert-crafted variant summaries of disease-associated/functional polymorphisms. HGMD Professional adds over 45,000 mutation reports per year.
How can HGMD Professional boost your content?
→ Using the public version of HGMD? Your lab does not have access to over 3 years of expert-curated data contained in HGMD Professional. See what else you’re missing here.
The “somatic version” of HGMD Professional, the Human Somatic Mutation Database (HSMD) is a new somatic database developed by QIAGEN that contains extensive genomic content relevant to solid tumors and hematological malignancies. Available as a web-based application, HSMD contains content from over 4.2 million mutations from two sources. Content is curated from over 420,000 real-world clinical oncology cases and the QIAGEN Knowledge Base.
HSMD provides gene-level, alteration-level, and disease-level information, including clinically observed gene and variant frequencies across diseases. Clinically relevant content in HSMD is placed into the perspective of clinical treatments, providing the links between biomarkers and targeted therapies, and is backed up with relevant scientific and clinical evidence. Users can easily search and explore mutational characteristics across genes, synthesize key findings from drug labels, clinical trials, and professional guidelines, and receive detailed annotations for each observed variant. In addition, users can interrogate a bibliography of over 150,000 variant-specific PubMed articles. HSMD also provides access to individual summaries of alteration-type specific information written by PhD scientists.
As QIAGEN Clinical Insights, QIAGEN’s clinical decision support platform for variant analysis, interpretation, and reporting, continues to be adopted by a growing number of molecular diagnostic labs around the world (The platform recently surpassed interpreting over 3 million NGS patient cases worldwide), the data contained in HSMD is increasing at a compounding rate. HSMD adds a minimum of 70,000 new clinical oncology cases each year.
How can HSMD boost your content?
→ Learn how a national cancer research center in Serbia is using HSMD to confidently identify meaningful mutations in somatic tumor testing here.
Explore, search, and test HGMD Professional and HSMD for free. To demonstrate the quality, flexibility, and simplicity of HSMD, QIAGEN Digital Insights offers complimentary, 5-day trials of both expert-curated database. Start your free trial today.
→ Request your free trial of HGMD Professional here.
→ Request your free trial of HSMD here.
The development of new cancer drugs is challenging, costly, and time-consuming. As translational research on cancer diagnostics and genomic profiling rapidly evolves, the ability to confidently and efficiently identify specific oncogenes and tumor suppressors involved in oncogenesis is becoming increasingly difficult.
This brief half-hour webinar is intended for biopharmaceutical and biotechnology professionals who need more efficient ways of discovering, developing, and repurposing drugs for oncology applications. During the session, attendees will explore a demonstration and a use-case presented by Dr. Kyle Nilson, providing insights into the Human Somatic Mutation Database (HSMD)—a new somatic database developed by QIAGEN that contains extensive genomic content relevant to solid tumors and hematological malignancies.
HSMD is an exceptional resource for biopharmaceutical and biotechnology companies, facilitating the confident evaluation of cancer-related genetic variations by granting access to real-world data. Powered by QIAGEN’s extensive artificial intelligence (AI)-enabled Knowledge Base, robust curation team composed of over 100 expert curators (MD and PhD level), and data from QIAGEN’s professional variant interpretation service (previously N-of-One), HSMD encompasses a vast repository of over 4.7 million meticulously curated genetic alteration findings and variant data over 500,000 somatic patient cases. Attendees will explore how HSMD enables biopharmaceutical and biotechnology companies to gain deeper insights into the molecular cancer profiles, identify therapeutic options, and develop strategies for finding new therapies for a particular cancer type or even for a particular patient.
Attendees will:
Interpretation of genomic variants in tumor samples still presents a challenge in clinical settings. Variant interpretation is fragmented across disparate databases, and aggregation of information from these requires building extensive infrastructure. The Human Somatic Mutation Database (HSMD) is an easy-to-use, somatic database from QIAGEN that contains extensive genomic content relevant to solid tumors and hematological malignancies. Pulling content from over 500,000 real-world clinical oncology cases and 40+ databases contained in the QIAGEN Knowledge Base, HSMD gives genetic counselors access to over 1.7 million somatic variants characterized in over 1,400 cancer-related genes. To demonstrate the efficiency and clinical utility of HSMD, we present a use-case for using the database to assess the biological and clinical relevance of anaplastic lymphoma kinase (ALK) gene.
About 3-7% of patients with non-small cell lung cancer (NSCLC) have rearrangements in the ALK gene. These genetic alterations are relatively rare compared with epidermal growth factor receptor (EGFR) or KRAS mutations (1). ALK rearrangements are often seen in people who don’t smoke and who are younger. These oncogenic mutations lead to the constitutive activation of the ALK tyrosine kinase domain, a protein that causes cancer cells to grow and spread. To date, several therapies have been developed to target ALK gene changes, known as ALK inhibitors. These include, Crizotinib (Xalkori), Ceritinib (Zykadia), Alectinib (Alecensa), Brigatinib (Alunbrig), and Lorlatinib (Lorbrena).
Therefore, clinical diagnostic labs that perform somatic genomic testing need to be able to define the precise biological function and clinical actionability of ALK mutations. However, given their relatively rarity, ALK mutations require thorough assessment and curation to accurately interpret their clinical significance and recommend effective treatment strategies.
HSMD is a web-based database that provides deep insight into small variants, such as SNVs, indels, frameshifts, fusions and copy number variants that have been clinically observed or curated from scientific literature to help users better understand and define precise function and actionability. Unlike other somatic databases, such as ClinVar and Genomenon that use crowdsourcing or human-absent machine learning, HSMD uses augmented molecular intelligence—the combination of machine learning and human curation—to curate each somatic variant. The result is higher quality data that is up-to-date, consistent, comprehensive, and accurate. This focus on human effort, review and certification is critical. It means clinical diagnostic labs can trust the data in HSMD and proceed with confidence to interpret and report somatic tests.
Here, we present a step-by-step use-case of how your clinical diagnostic lab can use HSMD to search and explore mutational characteristics across the ALK gene, synthesize key findings from drug labels, clinical trials, and professional guidelines, and receive detailed annotations for each observed variant.
HSMD is a web-based application. When you open the interface, the homepage provides five search options. Users can search by Gene, Alteration, Disease, Drug, or Clinical Trial (Figure 1).
Search by gene: When you search by gene in HSMD, you access the total number of genes listed in the database. You can then further narrow your search by viewing data from the QIAGEN Knowledge Base or focusing exclusively on clinically observed variants.
When you search for ALK p.F1174L in HSMD, you receive a description of the alteration with links to relevant literature, external links to the alteration in ClinVar, dbSNP, and OncoKB, and a summary of alteration details, including chromosome position, alteration type, functional impact, and population frequency (Figure 2).
Once you narrow your focus to searching for only clinically observed variants, you receive a table and distribution graph that shows the number of observed clinical cases for a particular gene across all cancer types.
Continuing the example using ALK p.F1174L, you can clearly see the alteration’s distribution by disease through a table and graph. As you scroll down, you receive information on it's biological impact, as well as the gene’s frequency in different populations (Figure 3). You can also view the biological impact and allele frequency (Figure 4).
Click to enlarge the images.
HSMD enables you to view relevant drugs and clinical trials for a ALK p.F1174L. You receive a list of drugs approved for use with ALK p.F1174L (Figure 5a), as well as recruiting clinical trials for that alteration (Figure 5b). In addition, HSMD provides an extensive bibliography for ALK p.F1174L, with clickable links to each article (Figure 6).
Click to enlarge the images.
As demonstrated by the use-case, incorporating HSMD into your somatic variant interpretation workflow enables you to easily search and explore mutational characteristics across genes, synthesize key findings from drug labels, clinical trials, and professional guidelines, and receive detailed annotations for each observed variant. With HSMD, you can efficiently ask and answer the following key questions:
HSMD is a one-stop shop for all the content a clinical diagnostic lab needs to assess the biological relevance and clinical actionable of somatic variants. QIAGEN Digital Insights offers free, no-obligation trials of HSMD. You can see what kind of content the database offers, explore the search functionality, and determine if this database can save you time and money.
Take the first step. Request a free trial of HSMD here.
Want to learn more?
Explore HSMD resources, videos, and use-cases here.
Need a FASTQ to final report solution for oncology NGS testing?
QCI Interpret for Oncology is an end-to-end solution for NGS data analysis, interpretation, and reporting that helps clinical diagnostic labs scale the process of FASTQ to final report.
QCI Interpret provides a comprehensive and flexible reporting system that automatically incorporates significant variants, key findings, annotation sources, and interpretation summaries. Reports can be fully customized to meet your lab’s brand and formatting requirements. This sample report is for a pan-cancer multimodal panel and shows results with TMB and MSI biomarkers and a KRAS alteration detected.
We are pleased to announce the release of the latest version of the Human Somatic Mutation Database, a new somatic database developed by QIAGEN that contains extensive genomic content relevant to solid tumors and hematological malignancies. HSMD 2.1.1 enhances the database with the latest cutting-edge cancer content, including new clinical trials, new drugs, and new variants that have been clinically observed or curated from scientific literature to help users better understand and define precise function and actionability.
HSMD 2.1.1 release highlights
View the full list of new content updates here.
About HSMD
Combining over 2 decades of expert curation and data from real-world clinical oncology cases, HSMD is a new somatic database from QIAGEN that serves as a single, trusted data source for clinical labs to validate, assess, and better understand the clinical significance of detected variants.
HSMD aggregates manually curated content from the QIAGEN Knowledge Base, the industry’s largest collection of biological and clinical findings, with data from over 500,000 real-world clinical oncology cases that have been analyzed and interpreted by QIAGEN’s professional clinical interpretation service, to eliminate the need to manually collect information across knowledge bases and provide deep genomic insight into the molecular characterizations of your patient’s tumor.
Easy to search with new content added weekly, HSMD enables users to explore key genes or mutations with driving properties or clinical relevance, and lets users search for associated treatment options, off-label therapies, resistance markers, and regional and/or disease-specific clinical trials.
Learn more about HSMD here.
[NEW!] HSMD Software Developer Now Available: Integrate HSMD into your in-house analytical tool for increased efficiency. You’ll be able to link out to the full HSMD online content via endpoints (API keys). HSMD Software Developer access provides integration keys for +1.5 million cancer-associated variants.
Dentro de las aplicaciones oncológicas, la capacidad de identificar alteraciones genéticas potencialmente accionables y explorar las vulnerabilidades moleculares del cáncer es cada vez más difícil.
Una nueva base de datos desarrollada por QIAGEN, la HSMD, contiene más de 2 décadas de contenido curado por expertos y datos de la QIAGEN Knowledge Base con más de 300.000 casos de oncología del mundo real para proporcionar una comprensión profunda y precisa de la accionabilidad de pequeñas variantes, como SNVs, indels y frameshifts, que han sido "clínicamente observadas" o consideradas por la literatura científica.
El 25 de mayo, únase a nuestros expertos en un tour virtual a la nueva base de datos y una presentación de sus características, capacidades y aplicaciones.
Dentro das aplicações oncológicas, a habilidade de identificar alterações genéticas potencialmente acionáveis e explorar as vulnerabilidades moleculares do câncer está se tornando cada vez mais difícil.
Um novo banco de dados desenvolvido pela QIAGEN, o HSMD, contém mais de 2 décadas de conteúdo com curadoria especializada e dados da QIAGEN Knowledge Base com mais de 300.000 casos oncológicos de mundo real para fornecer um entendimento profundo e preciso da acionabilidade de variantes pequenas, tais como SNVs, indels e frameshifts, que têm sido “observadas clinicamente” ou consideradas pela literatura científica.
No dia 4 de maio, junte-se a nossos especialistas para um tour virtual do novo banco de dados e apresentação dos seus recursos, capacidades e aplicações.
