Massive team effort. A huge thank you to the Ultima Genomics team, our clinical collaborators and sequencing team @nygenome.org
Look at the author list, it's huge! Takes a village. Super proud of trainees Aaron, Sam and Sri

Patient vignettes in lung cancer patients also show concordance with scans. A huge thank you to our collaborators Drs Altorki and Saxena

We looked at patients with urothelial cancer, and found strong correlation between tumor-informed and tumor naive measurements. Great collaboration with Dr Bishoy Faltas

Application 1: tumor-informed ctDNA detection. ppmSeq is perfectly suited for this. We sequence the tumor, and mine for mutations in the blood with ppmSeq. This enabled part per TEN MILLION ctDNA detection. PAR PER 10M. Insanity.

Error rate analysis in sperm gDNA (🙏 Gilad Evrony) and cell-free DNA shows comparable error rates to duplex technologies.

Initial benchmarking shows massive scalability of ppmSeq, ~40-60% of our reads encode dsDNA molecules. The more you sequence, the more get dsDNA
CRAZY STAT: ppmSeq is a PCR-FREE method that works with ONE NANOGRAM of input. ONE!!!

Turns out you can achieve this with PCR-free library prep, some (extremely) clever adapter design, and denaturation-free clonal amplification.

Not only that can we resolve multiple signatures, we highlight many instances of patients with very little ctDNA, but appreciable SBS31. Interesting implications that highlight our ability to comprehensively monitor patients for ctDNA and chemo genotoxicity

In @landau.bsky.social 's words ... "Amazing! So, what's next?"

Let's look at detecting multiple signatures. Can we resolve signatures from patients APOBEC3A (SBS2 + SBS13) AND platinum chemotherapy mutations (SBS31)
Phenomenal collaboration with Bishoy Faltas 🙏🙏🙏

Mutational signature fitting allowed for PLASMA-ONLY ctDNA detection! No more need for tumor sequencing!!

We leverage this ultra-clean data to perform single molecule mutation calling, allows us to match melanoma patient plasma signatures to UV radiation signatures

We developed error corrected WGS for the
Ultima Genomics platform, and measured error rates in the part per ten million range

We evaluated the error modes of different sequencers and challenged our ability to detect ctDNA with part-per-million dillutions ... it can be done with deep sequencing :)
Huge MRD implications (amongst others 🤫😉)