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GAO-21-426SP 1 (2021-03-30)

handle is hein.gao/gaolgm0001 and id is 1 raw text is: Science, Technology Assessment, and Analytics SCIENCE & TECH SPOTLIGHT: GENOMIC SEQUENCING OF INFECTIOUS PATHOGENS What is it? Genomic sequencing technologies decode a pathogen's genetic material by identifying the order of chemical letters of its DNA (or RNA, its chemical equivalent in some viruses). Each of four letters represents a chemical unit called a base. The sequence of the bases can reveal useful information for combatting disease. For example, sequencing of SARS-CoV-2 is used to track the spread of various strains, known as variants (see fig. 1). How does it work? Technologies for sequencing genomes of pathogens use chemicals to break up the DNA or RNA into small fragments. A first-generation method called Sanger sequencing repeatedly copies the fragments, fluorescently tags the copies, sorts them, and reads the letters of the genetic code. Sanger sequencing produces accurate data, but is slow because it reconstructs the genomic sequence base by base. This makes it expensive for large-scale sequencing of whole genomes. Newer technologies such as next generation sequencing (NGS) can read much longer strings of letters from samples. One NGS technology works similarly to Sanger sequencing, but works in parallel on different parts of the genome at the same time, followed by computational reconstruction of the entire genome. Another type of NGS technology uses electrical current to thread long, single DNA strands through tiny pores of a membrane to identify the letters of the code. NGS can process millions to billions of sequences at the same time. Compared with Sanger sequencing, NGS reduces cost by over 1,000 times for larger samples. It also greatly reduces the time to determine the whole genome sequence of pathogens from multiple clinical samples, potentially allowing for more rapid discovery of variants. How mature is it? First-generation sequencing is often used to confirm results of NGS. NGS is relatively new to the public health field, but is used to augment surveillance (i.e., data collection and analysis) for SARS- CoV-2 in the U.S. and overseas. New technologies are allowing greater access to sequencing capabilities by making NGS portable, faster, and more affordable (the cost of one sequence run is now one-millionth of what it was two decades ago). Genomic sequencing technologies enable many different areas of infectious disease study. For example, they enable genomic epidemiology-the science of using pathogen genomic data to determine the distribution and spread of an infectious disease in a group of people or animals, and the application of this information to respond to health problems (see fig. 2). of known variants Track community spread of variants CCU-CC CCCG CCucc C CUC Infected person Sample 'seTgeted 7segment Variant 1 Variant 2 Variant 3 Variant 4 Identification of variant type Source: GAO. i GAO-21-426SP Sequencmg macnme ACCGUA ACC GAA ACCC A ACC UA Compare to known variants Use of genomic sequencing in the identification of infectious pathogen variants. A, C, G, and U represent letters of the genetic code. Source: GAO. i GAO-21-426SP F Use of mobile genomic sequencing technology to track the community spread of infectious pathogen variants. A, C, G, and U represent letters of the genetic code. Wider use of NGS requires more laboratories to have infrastructure such as DNA extraction expertise, computer capacity and storage, and appropriately trained personnel to analyze and interpret sequencing data. I/ (PPORTUNITIES * Public health response. Genomic sequencing has the potential to transform public health approaches to infectious disease surveillance and treatment. It may allow identification of new pathogen variants shortly after they appear, generation of more data to estimate the prevalence of variants in populations, and eventually development of targeted treatments. For example, in February 2021, CDC GAO-21-426SP Genomic Sequencing

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