Wednesday, May 15, 2024
5/15/2024
Project Summary While general DNA sequencing is becoming a standard laboratory technique, no technology to date has been able to combine the features of high-accuracy (>99.9%) and long-reads (10s to 100s of kilobases), an absolute necessity to broadly transition DNA sequencing into a practice for genomic and precision medicine with diagnostic applications. While single-molecule sequences (SMS) approaches have emerged as very promising toward overcoming read-length limitations posed by next generation sequencing (NGS) technologies, it is unfortunately commonplace for these SMS technologies to yield error rates that exceed 4%, and higher accuracy is needed to obtain medically-relevant sensitivity/specificity metrics. During this program, Electronic BioSciences (EBS) proposes to demonstrate high-accuracy (>99.9%) SMS via electronic strand “flossing,” without using processive enzymes, which will lay the foundation for the eventual development of the first high-accuracy, long- read SMS system. Here, EBS will demonstrate high-accuracy, single-molecule consensus sequence calling using iterative reads on individual DNA strands. The accomplishments made during the program will enable exciting progress within the sequencing field, including fundamental investigations into genome assembly, sampling profiling, general biological studies (e.g., telomer length, microsatellite sequencing, etc.), and eventually clinical diagnostics, feats that are otherwise challenging to perform with currently available technology. As a result, this work will help improve broad-scale biodiversity and metagenomic studies, clinical diagnostics, and population care.
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