Tumor mutational burden (TMB) is rapidly gaining acceptance in oncology research as a key biomarker and indicator of tumor response to immune checkpoint inhibitors. Whole-exome sequencing (WES) of tumor-normal pairs is the reference standard for the calculation of TMB; however, given the cost and other workflow implications of WES, TMB is frequently derived from targeted next-generation sequencing panels.

This scientific poster from IDT describes the measurement of TMB using VariantPlex Pan Solid Tumor and VariantPlex Complete Solid Tumor panels utilizing anchored multiplex PCR chemistry for error correction and bias mitigation.

For Research Use Only. Not for use in diagnostic procedures.

This 20-minute, on-demand presentation sheds light on crucial aspects of bringing a genetic test to market. It covers:

• Advantages of FDA-Cleared Devices: Explore the benefits of utilizing US FDA-cleared Oragene Dx and ORAcollect Dx saliva collection devices in genetic tests and molecular diagnostics.

• Navigating Regulatory Considerations: Gain insights into the regulatory landscape for IVDs and LDTs and the strategic path for bringing genetic tests to market while complying with evolving regulations.

• Ease of Use and Customization: Understand the evidence supporting the ease of use of saliva collection devices with U.S. FDA general clearance. Learn how test kits can be customized to meet specific requirements, with streamlined offerings for test providers, and enabling a convenient experience for patients.

Speakers:

• Austin Udocor, Director, Regulatory Affairs, DNA Genotek Inc

• Tara Crawford Parks, Ph.D., Senior R&D Manager, DNA Genotek Inc

Please click here for the companion eCase study video.

Antibody development, scale-up, and mass manufacturing remain complex processes with many pitfalls and restarts. Part of the challenge is that the skill sets needed for each of the three main steps — development, scale-up, and manufacturing — are considerably different, requiring the commercialization team to master diverse technologies and techniques. Further, the team is faced with decisions on outsourcing parts of the process or investing in in-house expertise and capital expenditures. Often, when a project has narrow performance specifications or tight launch deadlines, seeking out an experienced partner like MilliporeSigma is prudent. This talk covers the key steps in the modern antibody development process for diagnostic assays using advanced technology and discusses case studies in which MilliporeSigma's R&D and manufacturing teams solved some of the toughest challenges in antibody commercialization.  

Please click here for the companion eCase study video.

Biofidelity is a pioneer in the genomic technology space, and the UK-based company’s mission is to unlock the benefits of precision medicine for cancer patients. Its technologies can be used for early detection, precise diagnosis, and routine monitoring applications in oncology.

This white paper from LGC SeraCare explains how working closely with LGC Clinical Diagnostics ensures that Biofidelity is provided with the high-quality, bespoke next-generation sequencing reference materials that the company needs to validate its technology for translation into clinical practice.

Proficiency testing allows a laboratory to evaluate if its test performance is satisfactory for the intended clinical purpose. It enables inter-laboratory comparisons by providing the same material to participants. This is important for non-invasive prenatal tests (NIPS or NIPT) since they are not FDA-approved diagnostic tests and are only intended for screening.

This white paper from LGC SeraCare describes a study examining the 2022 College of American Pathologists NIPT participant summary report regarding a case that showed a disparity in fetal sex chromosome status between the participants, with findings supporting the importance of appropriate diagnostic follow-up, genetic counseling, and clinical correlation in prenatal testing.

The BRCA1 and BRCA2 tumor suppressor genes limit DNA damage. Consequently, loss-of-function mutations in these genes lead to increased incidence of breast, ovarian, and prostate cancer. Accurate detection of BRCA variants is paramount for patients with somatic cancer to guide treatment strategies, such as eligibility for PARP inhibitor therapy, and for individuals carrying inherited mutations to consider preventive actions. However, 27 percent and five percent of pathogenic mutations in BRCA1 and BRCA2, respectively, are large genomic rearrangements (LGRs) that are particularly difficult to detect in PCR and targeted NGS-based assays. Therefore, the development of assays that consistently detect BRCA1/2 LGRs will require reliable reference materials for validation, troubleshooting, and routine quality control.

This scientific poster from LGC Seracare describes the development and multi-platform validation of a set of novel multiplexed reference materials containing 20 clinically relevant BRCA1/2 variants, including 11 large genomic rearrangements.

Homologous recombination deficiency (HRD) arises when defects in DNA repair pathways occur, leading to genomic instability. HRD status is an emerging therapeutic biomarker; NGS assays that measure it can be used to stratify ovarian and breast cancer patients and determine eligibility for clinical trials, PARP inhibitors, and platinum-based therapies. Seraseq FFPE HRD reference materials were developed to cover a range of genomic instability scores to help NGS HRD assay validation and development.

This scientific poster from LGC SeraCare discusses a multi-site evaluation across various platforms of high-positive, low-positive, and negative HRD reference materials.

Cancers can be caused by a multitude of distinct genetic abnormalities, and each tumor is unique. Dozens of new targeted therapies have been developed in recent years, but the challenge of providing optimal care to cancer patients lies in the ability to match the genetic profile of the tumor to the most appropriate therapy. Advances in next-generation sequencing (NGS) technologies have enhanced the identification of hundreds of mutations that may contribute to disease progression, and the development of new diagnostic NGS assays is continually evolving. These assays can profile genetic mutations to enable precision diagnostics, personalized treatment selection, stratification of patients for clinical trials, and improved disease monitoring.

This white paper from LGC SeraCare describes the role reference materials play in developing and validating robust precision oncology assays that can perform with the accuracy, sensitivity, and reproducibility required for clinical use, as well as considerations for selecting the most appropriate provider of reference materials.

The detection of minimal residual disease (MRD) in acute myeloid leukemia (AML) can present a challenge because it can require detecting just a few malignant cells within thousands — if not millions — of normal cells. One of the major challenges associated with the development and validation of assays for MRD in AML is the absence of cell-based reference materials that feature diverse mutations that may be encountered clinically. To begin to address the need for standards, LGC SeraCare developed full-process cell-based reference materials that contain several mutations and formulated them at concentrations down to one in 100,000 in a background of normal leukocytes.

This scientific poster from LGC SeraCare describes the generation and validation of cell-based and ccfDNA-based reference materials for the development and validation of assays for the detection of MRD in AML.

This case study from Elucidata details how a US-based cancer diagnostics company partnered with Elucidata to streamline their data management workflow — from ingestion, preprocessing, and curation to insight generation — for raw single-cell multiome data to identify diagnostic markers for AML.

Their research team utilized the Google Cloud Platform (GCP) to store and use/reuse the raw data. However, the process of uploading large files from the sequencer to GCP, processing them, and subsequently downloading them for additional analysis proved to be laborious and error-prone, requiring redundant effort. Moreover, the absence of standardized naming conventions or classifiers for data storage made it challenging to meet the company's evolving data requirements. They were in dire need of a reliable and efficient data management system.

Mycoplasma contamination constitutes a serious concern for cell culturists as these bacterial strains are a common cause of cell line contamination affecting roughly 15-35 percent of cell cultures and endangering almost all aspects of cell physiology. This is of particular concern for research laboratories and commercial facilities that employ cell lines in the development and manufacture of cell-derived biopharmaceutical products for medical use. Contamination of cell substrates used in the production of biopharmaceuticals poses a potential safety risk for patients and presents a serious economic risk for manufacturers in the event of batch adulteration or a product recall. To minimize these risks, routine testing for mycoplasma is performed throughout the product manufacturing and development process. This white paper from ATCC discusses the effects of mycoplasma contamination, how this form of adulteration can affect cell-based drug development, and several quality control techniques and related products that can be used in the detection of mycoplasma contamination.

Carbohydrates in the form of capsular polysaccharides and lipopolysaccharides constitute a major component of the cellular surface for many bacterial species. In Streptococcus pneumoniae, capsular polysaccharides function as major virulence factors that protect the bacterium from phagocytosis by host immune cells. Within this species, capsular polysaccharides exhibit enormous structural diversity, resulting in significant differences in immunogenicity and antigenicity. In turn, this has presented numerous challenges to the prevention and serological analysis of pneumococcal infections. This white paper from ATCC discusses the importance of capsular polysaccharides in S. pneumoniae infection and describes the use of purified serotype-specific polysaccharides in developing and evaluating pneumococcal vaccines, verifying novel immunoassays, and tracking bacterial disease epidemiology.

Many CFTR panels have been designed using variant information from disease databases that are heavily skewed toward individuals with European ancestry. Recent studies have shown that many CFTR carriers may be missed in ethnically diverse populations**, including the US demographic. To address these coverage gaps, Asuragen scientists consulted recent, large-scale population studies in the development of the AmplideX PCR/CE CFTR Kit* to ensure key CFTR variants could be detected across ethnic groups. Read the white paper “Making Coverage Count” to learn more about the importance of equitable CFTR coverage in diverse populations.

*For Research Use Only. Not for use in diagnostic procedures.

**Based on pathogenic alleles in the U.S. demographic from Beauchamp KA, et al. Genet Med. 2019.

Developing, optimizing, and launching a lateral flow assay (LFA) test is never routine or easy. Although the plethora of test strips that popped up during the COVID-19 pandemic might give the illusion these assays are simple, developers know — or soon learn — that the development of those streamlined plastic cassettes poses key technical challenges that can delay assay launches.

Lateral flow test strips are complex devices, and designing and making them requires significant knowledge about diverse fields including biochemistry, immunochemistry, membrane engineering, and nanomaterials. Experience suggests an assay team is likely to encounter one or more development challenges for which external expertise might be beneficial.

This white paper from Millipore Sigma offers strategies to address challenges in developing and launching lateral flow assays for companies or researchers wanting to convert an existing IVD to a lateral flow design or to develop a new assay.

Laboratories must conduct assay validations to ensure that accurate, reliable data is provided to physicians and patients, but it is not a routine task for most labs. Laboratory-developed test (LDT) validation is a complex task, requiring specialized skills. Because most labs go through the validation process infrequently, in-house teams often have limited experience. If not carefully planned, mistakes in the validation process can lead to unexpected expenses and timelines that can stretch up to 12 months. For labs running on tighter margins than ever before, an efficient and cost-effective validation process is critical.

This white paper from Streamline Scientific discusses the challenges in LDT validation, how mistakes early in the validation process can lead to delays, repeated testing, and added costs, and how a validation consulting service can ensure the process runs smoothly.