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Today, Sculpta releases the first demonstration of bioorthogonal barcoding ("bobcoding"), the process by which we:
1) covalently attach oligonucleotide barcodes to RNA at multiple internal positions with two-step chemistry, and 2) perform a multiplexed reverse transcription reaction to generate barcoded cDNA libraries with >99% barcoding accuracy.
To the best of our knowledge, it is the first time ever that either of these steps have ever been performed by anyone. No one has ever broken the barrier of multiplexing prior to any enzymatic step in library preparation, driving simplicity and higher data quality. Instead of other methods that add 0 or 1 barcode, we add one barcode every ~300bp, adding redundancy and fidelity to RNA measurements.
In our first application described in our pre-print below, we used bobcodes to create the first RNA isoform-resolved drug screening platform. It beats Novartis' DRUG-seq platform by:
- generating full length transcript capture of RNA isoforms, instead of just 3' end counting
- capturing 25-fold more RNA splicing events
- reducing barcode swapping by 10-fold
- using 18 fewer PCR cycles (~250,000 less amplification)
- reducing sample-to-sample variability in gene expression measurements
- eliminating costly and cumbersome library fragmentation/tagmentation steps completely
- reducing workflow complexity and number of steps
- reducing overall protocol duration by ~25%
Though our chemical barcoding method improved transcriptomic data quality while also being simpler and faster than all existing methods, the implications of this work go well beyond this particular use case:
The gate to greater applications of AI in transcriptomics is not a lack of compute. Nor is it a lack of data volume. The elephant in the room has always been our limited ability to faithfully and accurately measure cellular RNAs.
Sculpta now has line of sight to build what we call the first ground truth transcriptomics platform [for single cell, spatial and more] for the future of biological research, drug development and AI-enabled discoveries for the betterment of human health and longevity.
[PS Until the kind folks at bioRxiv get through the apparent backlog of AI slop submissions, Sculpta will host the pre-print PDF on our website. You can sign up for product offerings and other updates at this link too]
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