Accurate sequence information is essential to the design of the primers and probes that are critical to the success of polymerase chain reaction (PCR) assays and Real-Time PCR. The continuing genetic evolution and diversity of infectious diseases and emerging pathogens are therefore a significant challenge for PCR assays.1 In fact, monitoring and responding to sequence changes is essential for companies that produce—and want to keep producing—effective assays. It should be no surprise to anyone then that Roche Molecular Diagnostics, a pioneer in PCR technology, is also a global leader in monitoring these sequence changes.2
Greater than twenty years at the forefront
In 1998, at the International AIDS Conference in Geneva, Roche inaugurated the Global Surveillance Program.2,3 Initially designed solely to monitor changes in the HIV-1 genomic sequence, the program and its database have since expanded to cover the pathogen targets of many Roche diagnostic assays and also to include bioinformatics pipelines to assess test performance in the Roche mastermix. Models are built and tested in wet lab experiments to determine parameters critical to assay design in the Roche mastermix. This has resulted in a better understanding of our mastermixes tolerance and led to more robust designs.
The Global Surveillance Program includes sequencing assays for multiple infectious diseases:
- Viruses - HIV-1, HIV-2, HBV, HCV, HPV, CMV, EBV, BKV, HEV, HAV, Zika, WNV, B19, ChikV, Dengue, HSV-1, HSV-2, Influenza A, Influenza B, RSV, SARS-CoV-2.
- Parasites - Babesia, TV.
- Bacteria - MG, CT, NG, MTB and MRSA.
The Program’s efforts and many achievements have played a monumental role in helping to maintain, and improve, the reliability of molecular assays. Innumerable researchers, physicians and patients around the world have benefited as a result.2,4
Leveraging initiative and collaboration
The Global Surveillance Program is not alone in its mission. Instead, the program has leveraged Roche’s extensive resources and those of other entities in fruitful, synergistic collaborations. For example, the Global Surveillance Program regularly accesses important public databases based both in the United States and in other countries. These include, but are not limited to, those of the Los Alamos National Laboratory and the National Institute of Health’s GenBank database along with Global Initiative on Sharing All Influenza Data (GISAID).4 In addition, collaborations with researchers worldwide to understand performance of approved tests in commercially operating facilities further enhances Roche’s understanding to optimize and improve our bioinformatics tools using wet lab data.
Exhaustive process, exceptional rewards
The sequences obtained, due to the efforts of the Global Surveillance Program, are carefully preserved and archived through a rigorous process.4
- After Roche receives clinical samples, sequences containing the assay target regions are typically amplified and sequenced.
- The sequences are analyzed to determine genotype, strain and/or subtype, and compared to previously generated sequences in both our internal database and public databases.
- The sequences are aligned to assay primer and probe sequences. Differences are noted and enumerated. Roche-developed Bioinformatics tools are used to predict the performance of diagnostic assays based on proprietary algorithms calibrated by experimental results from previous samples, panels, or artificial template testing.
- Information from these alignments and predictive tools is used to assess the overall performance of assays as information in sequence databases continues to expand, and aids in the design of future assays.
The result is continuous analysis and improvement, leading ultimately to better diagnostics, better prognostics and better disease management.
Creating standards and strategies for the future
Roche’s Global Surveillance Program is designed to make a positive, lasting impression on the field of molecular diagnostics in many ways. One is by facilitating epidemiological investigations that help identify trends responsible for the spread of infection. Another is by building on ongoing collaborations and continually pursuing new ones. Roche always continues to broaden its own database and among efforts currently underway are those to obtain diverse samples for each new asset design efforts from regions around the world to develop the most optimized global solution.4
In fact, the Global Surveillance Program is an integral part of Roche Molecular Diagnostics product development at multiple points in the process, including research and development, regulatory submission and post-launch support.4
The Global Surveillance Program is a powerful example of Roche’s unique and robust commitment to the researchers, physicians, and patients working to fight disease and maintain health around the world. As the demands of their mission are constantly evolving, so are we. We are committed not only to keep pace, but to lead.