New Benchmark Report from NIST, Baylor College of Medicine and DNAnexus Helps Provide Accurate Identification of Variants in Challenging Medically Relevant Genes

New Nature Biotechnology publication advances efforts to improve genome sequencing information for diagnosis and treatment of disease

Researchers from National Institute of Standards and Technology (NIST), Baylor College of Medicine and DNAnexus, Inc., together with other members of the Genome in a Bottle (GIAB) consortium, announce the publication of a comprehensive benchmark dataset comprising 273 challenging medically relevant autosomal genes that are associated with the development of diseases such as homocystinuria and spinal muscular atrophy. These datasets and a corresponding benchmark report were published yesterday in Nature Biotechnology.¹

Co-corresponding authors Dr. Fritz Sedlazeck of Baylor, Dr. Justin Zook of NIST and Dr. Jason Chin of DNAnexus led the team of researchers in focusing on a set of medically relevant genes that had been excluded from previous benchmarks due to their complexity. Using HiFi sequencing reads, the GIAB team identified thousands of single nucleotide variants, structural variants and large insertions and deletions in those genes in the two most commonly used human reference genomes. They also corrected errors in several medically relevant genes, improving variant recall accuracy to 100%.

“This benchmark will lay the groundwork for novel methods to improve our understanding of variability across these challenging but medically important genes,” said Sedlazeck, associate professor at the Human Genome Sequencing Center at Baylor. “Our findings can enable insights into new diseases gene candidates and treatments for a multitude of diseases.”

“This benchmark was made possible by a team of researchers who are committed to supporting research into disease-associated variation across the genome, including diseases like spinal muscular atrophy caused by variation that is challenging to detect,” said Zook, Biomarker and Genomic Sciences Group Leader at NIST. “But there is still work to be done. Future studies will create benchmarks for complex regions of variation in the genome that are still challenging to characterize even with long reads.”

“To-date, common bioinformatics tools have been unable to characterize many clinically-relevant genes because they are difficult to assess with current short-read sequencing technologies due to their complexity and repetitive nature,” said John Ellithorpe, PhD, president at DNAnexus. “We are proud that DNAnexus researchers are able to contribute to important scientific advancements and benchmarking reports such as this one, and we hope that these efforts will contribute to the advancement of the diagnosis and understanding of various genetic diseases and their heritability.”

Full details of the benchmark and the methods that were used to generate it are described in a paper published in Nature Biotechnology. The report will also be highlighted during an upcoming webinar A New Benchmark in Exploring Variants in Challenging Medically Relevant Genes on March 3, 2022. Register for the webinar here.

About Baylor College of Medicine

Baylor College of Medicine (www.bcm.edu) in Houston is recognized as a health sciences university and is known for excellence in education, research and patient care. It is the only private medical school in the greater southwest and is ranked 22^nd among medical schools for research and 17^th for primary care by U.S. News & World Report. Baylor is listed 20^th among all U.S. medical schools for National Institutes of Health funding and No. 1 in Texas. Located in the Texas Medical Center, Baylor has affiliations with seven teaching hospitals and jointly owns and operates Baylor St. Luke’s Medical Center, part of CHI St. Luke’s Health. Currently, Baylor has more than 3,000 trainees in medical, graduate, nurse anesthesia, physician assistant, orthotics and genetic counseling as well as residents and postdoctoral fellows. Follow Baylor College of Medicine on Facebook (http://www.facebook.com/BaylorCollegeOfMedicine) and Twitter (http://twitter.com/BCMHouston).

About DNAnexus

To improve human health, researchers and clinicians need to access complex and sensitive biomedical data and innovative technologies that can enable novel insights. However, these data are often incompatible or difficult to process. DNAnexus is the leading bioinformatics company that facilitates secure access and utilization of biomedical data while supporting collaboration across internal and external teams. From providing an end-to-end integrated diagnostic R&D and production bioinformatics platform, enabling national biobank biomedical initiatives to provide pharmaceutical companies with a multi-omics data science platform for new target drug discovery, DNAnexus empowers the healthcare and life sciences industry to transform how they leverage biomedical data to accelerate scientific discoveries and deliver better patient care. For more information on DNAnexus, please visit www.dnanexus.com or follow the company @DNAnexus.

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¹ Wagner, J., Olson, N.D., Harris, L. et al. Curated variation benchmarks for challenging medically relevant autosomal genes. Nat Biotechnol (2022). https://doi.org/10.1038/s41587-021-01158-1

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New benchmark report from @NIST, @BCM_HGSC, @dnanexus published in @NatureBiotech. Learn how accurate identification of variants in challenging medically relevant genes helps improve genome sequencing info for diagnosis & treatment of disease