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Enabling an economical genome-skimming pipeline for natural history specimen collections

Funder: UK Research and InnovationProject code: BB/Z516065/1
Funded under: BBSRC Funder Contribution: 892,412 GBP

Enabling an economical genome-skimming pipeline for natural history specimen collections

Description

Natural history specimen collections, such as those curated in museums and herbaria across the UK, are invaluable resources for bioscience research, representing an enormous labor effort over decades and centuries, used to create an archive of millions of physical specimens identified to the highest standard. Digitization of these specimens, including of DNA sequences commonly used in molecular genetic and ecological research, would hugely improve their accessibility to the wider biological community, improving by orders of magnitude the species diversity represented in public sequence databases. This will greatly improve our ability to detect and understand organisms and gene sequences relevant to the BBSRC remit, including agricultural pests, crop cultivars, pollinators, parasites, vectors of pathogens, and remains of ancient peoples. However, the vast majority of these specimens were preserved prior to the molecular era, and as such the condition of DNAs in these specimens is poor - fragmented to <100 base-pairs, and chemically damaged, making them impossible to access using popular techniques such as "DNA barcoding". Short read sequencing provides a solution to this quandry through economic brute force - we are now able to sequence over a billion DNA bases for circa £5-10. In particular, we are now able to "skim-read" the genome for a total economic cost of £20-30/specimen, generating high-quality sequences of markers of high relevance in species identification such as mitochondrial and chloroplast genomes and ribosomal DNA. Deeper sequencing of these specimens can also be used to call population variants or mine for specific nuclear sequences of relevance in biomedicine and agriculture. This award will allow the Natural History Museum to purchase instruments enabling our molecular labs to offer the world's first specialist service for "genome skimming" of historical specimens, receiving tissue specimens from users and returning data for under £30/specimen. We will rely on the instruments this award funds to achieve this vision in two ways. Firstly, user-friendly liquid handling/automation instruments will act as a "force multiplier" for a lab technician, enabling several 100s of specimens to be processed in the time that it would take to process a few 10s of specimens manually. These instruments, which dispense sustainably and economically with dramatically lower use of disposable plasticware, would also enable us to cut the volume of sequencing library prep reactions, reducing this cost to a few £/specimen. Secondly, we would sequence the samples in-house, using special read formats appropriate to the highly fragmented nature of historical DNA, on a new generation of sequencing instruments. These deliver field-leading accuracy and cost-per-base (for us, circa £10/skim), at a purchase cost ca. 1/4 that of high-throughput instruments used in specialist centres. With 5 project partners from some of the UK's most prominent natural history collections, we will apply this service to skim 1000s of specimens in the first year of operation, before opening to general submission. This service, building on the NHM's expertise with these challenging templates, will render molecular sequences from historical samples (all deposited publicly by default) accessible to a wide audience of comparative and applied biologists.

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