A genome-first multiomic approach to diagnosis

Did you know that one in 10 Americans have a rare disease and it can take five or more years, on average, for a person with a rare disease to get an accurate diagnosis? That’s more than 30 million patients navigating long, costly, and uncertain diagnostic odysseys. Healthcare doesn’t move forward when patients spend years on that diagnostic journey. It moves forward when we translate scientific research and innovation into real-world impact for patients. Behind every appointment and test is a patient and family searching for clarity. We must strengthen the bridge between discovery and patient care to help shorten the amount of time it takes to receive answers. The good news is there’s been significant progress made in recent years, and there are already diagnostic options today that can transform the patient care trajectory. Enter whole genome sequencing (WGS). WHOLE GENOME SEQUENCING At Baylor Genetics, we believe the biggest leap forward for rare disease diagnosis will happen when WGS becomes the standard of care and is used as a first-line tool for all patients. This means getting access to comprehensive testing earlier in the diagnostic journey, which is exactly when it’s most impactful. WGS is already recommended across multiple professional society guidelines for a variety of clinical indications such as intellectual disability, developmental delay, congenital anomalies, and unexplained epilepsy. And even though we’ve seen strong momentum in guidelines, insurance coverage for WGS varies. Today, approximately 58 of U.S. commercial payers and 73 of Medicaid programs provide coverage for WGS in outpatient settings, according to our internal data from March 2026. While there is growing recognition across the healthcare community, there is still work to be done to drive systemic change for a genome-first approach to care, including accelerating access to testing, clinical implementation, increasing insurance coverage, and expanding clinical guidelines. The science is here and the system is catching up. WHY A GENOME-FIRST APPROACH MATTERS WGS consistently demonstrates the highest diagnostic yield compared to whole exome sequencing and panel-based genetic testing, with reported diagnostic yields ranging from 27 to 43. Its strength lies in its breadth and ability to analyze up to 98 of the genome. This offers a broader analysis and deeper insight into disease mechanisms, ultimately helping to inform more accurate diagnoses and support informed clinical care decisions. The genome is highly complex. While we can uncover a lot about an individual’s DNA with a single technology like WGS, it is important to acknowledge that WGS will not diagnose every patient, due to inherent biological and technical limitations. This leaves a persistent diagnostic gap. The biggest opportunity to close this gap lies in a more comprehensive diagnostic approach. It starts with WGS as the foundation and layers in complementary technologies. These should be applied selectively and strategically, to interrogate difficult-to-map genomic regions and variants with uncertain clinical significance. Additional technologies, such as RNA sequencing, optical genome mapping (OGM), or long-read sequencing (LRS), can expand WGS’s clinical impact by enriching interpretation and uncovering deeper genetic insights. This comprehensive approach provides an even more precise view of the genome and ultimately clearer answers for patients who need them most. A practical framework like this can help address complex and unresolved patient cases, and brings us one step closer to closing the diagnostic gap. If we start to think about WGS as a foundation for diagnosis, while layering in other modalities as needed, we can help bring moreclarity and answers for patients who have been tirelessly waiting. INNOVATION AND REANALYSIS Another important consideration as science and technology continue evolving is for patients who had a negative or unclear result with WGS years ago, and still remain undiagnosed. Reanalysis allows a reassessment of the patient’s genetic data and clinical presentation in light of new phenotypic information, research, insights, and/or analysis tools. Looking at the data again can uncover things like whether a new gene-disease association has been discovered or if patients may be candidates for complementary technologies that have since been introduced, like OGM and LRS. This process often offers patients a renewed opportunity to uncover meaningful answers. FINAL THOUGHTS The future of rare disease diagnostics will not be defined by any single technology, but by how effectively we bring them together to improve patient care and outcomes. By moving beyond a one-dimensional view of the genome and embracing a more integrated, multimodal approach, we can begin to close the diagnostic gap that persists for too many patients and families. The past decade’s progress has been remarkable, but the work ahead is even more important. It is our responsibility to continue advancing the science, challenging today’s limitations, and building more comprehensive solutions that turn data into diagnoses, and diagnoses into meaningful care. Kengo Takishima is chairman and CEO of Baylor Genetics.