Sign in

Alex

@alexpellancheng.bsky.social
91 followers 278 following 27 posts

ohhhmics | Associate Professor at ETSmtl & CRCHUM | 🐶🧬☕️ 🐥 pellanchenglab.github.io/#join

PostsRepliesMedia
Alex @alexpellancheng.bsky.social · 14/08/2025
We believe that these sorts of innovation will greatly serve the at large genomics community. More innovation = more options for scientists = more discoveries. Super exciting. Let's gooooooo!
000
Alex @alexpellancheng.bsky.social · 14/08/2025
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
131
Alex @alexpellancheng.bsky.social · 14/08/2025
Patient vignettes in lung cancer patients also show concordance with scans. A huge thank you to our collaborators Drs Altorki and Saxena
100
Alex @alexpellancheng.bsky.social · 14/08/2025
We looked at patients with urothelial cancer, and found strong correlation between tumor-informed and tumor naive measurements. Great collaboration with Dr Bishoy Faltas
100
Alex @alexpellancheng.bsky.social · 14/08/2025
But what if you don't have the tumor? DOESN'T MATTER. ppmSeq is so error robust that you don't need tumor sequencing to detect ctDNA. Hello, new era of tumor-naive patient monitoring.
100
Alex @alexpellancheng.bsky.social · 14/08/2025
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.
100
Alex @alexpellancheng.bsky.social · 14/08/2025
ppmSeq is a broad DNA sequencing method. The applications are endless. We looked at 2:
100
Alex @alexpellancheng.bsky.social · 14/08/2025
Error rate analysis in sperm gDNA (🙏 Gilad Evrony) and cell-free DNA shows comparable error rates to duplex technologies.
100
Alex @alexpellancheng.bsky.social · 14/08/2025
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!!!
100
Alex @alexpellancheng.bsky.social · 14/08/2025
You can ID Watson and Crick strands using a mismatched adapter, and single-stranded artifacts cause a conflicting sequencing signal > this is naturally encoded as a low-quality base. You then just filter out the error!
100
Alex @alexpellancheng.bsky.social · 14/08/2025
Turns out you can achieve this with PCR-free library prep, some (extremely) clever adapter design, and denaturation-free clonal amplification.
100
Alex @alexpellancheng.bsky.social · 14/08/2025
What if we encode double stranded DNA into a single sequencing read? One read = one dsDNA molecule
100
Alex @alexpellancheng.bsky.social · 14/08/2025
Beautiful works from amazing scientists seeks to address this. See work from Hoang (BotSeqS), Abasbal (NanoSeq) and Bae (CODEC) with bottlenecking and concatenation strategies. We took a different approach.
100
Alex @alexpellancheng.bsky.social · 14/08/2025
State of the art error corrected sequencing methods incorporate some form of duplex sequencing, when both strands of a molecule are read to correct for error This is ultra accurate, but also inefficient. You need to sequence a lot of reads to get modest amounts of duplexes
100
Alex @alexpellancheng.bsky.social · 14/08/2025
Highly accurate sequencing OR high throughput? We refuse to choose. Introducing ppmSeq, a method built to deliver both. Our latest from the @landau.bsky.social lab with Ultima Genomics 👀👀👀 See ⬇️ for a primer on the next frontier of genomics www.biorxiv.org/content/10.1...
biorxiv.org
Paired plus-minus sequencing is an ultra-high throughput and accurate method for dual strand sequencing of DNA molecules
Distinguishing real biological variation in the form of single-nucleotide variants (SNVs) from errors is a major challenge for genome sequencing technologies. This is particularly true in settings whe...
1162
Alex @alexpellancheng.bsky.social · 11/04/2025
Thank you! An abbr version is in the Methods section (past the references, Cell-free DNA library preparation header). E-mail me if you’d like a step-by-step protocol!
110
Alex @alexpellancheng.bsky.social · 11/04/2025
And that's it for now! A huge thank you to the patients and funders. This was a huge collaboration and this project simply does not happen without strong support from @nicorobine.bsky.social @gmboland.bsky.social @jeddwolchok.bsky.social @nygenome.org and a ton more
020
Alex @alexpellancheng.bsky.social · 11/04/2025
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
100
Alex @alexpellancheng.bsky.social · 11/04/2025
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 🙏🙏🙏
110
Alex @alexpellancheng.bsky.social · 11/04/2025
Mutational signature fitting allowed for PLASMA-ONLY ctDNA detection! No more need for tumor sequencing!!
110
Alex @alexpellancheng.bsky.social · 11/04/2025
We leverage this ultra-clean data to perform single molecule mutation calling, allows us to match melanoma patient plasma signatures to UV radiation signatures
100
Alex @alexpellancheng.bsky.social · 11/04/2025
We developed error corrected WGS for the Ultima Genomics platform, and measured error rates in the part per ten million range
120
Alex @alexpellancheng.bsky.social · 11/04/2025
Cost effective sequencing for tumor-informed ctDNA detection will let you sequencer deeper, or sequence more samples.. but can we develop tools that are only sustainable with cheaper sequencing?
100
Alex @alexpellancheng.bsky.social · 11/04/2025
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 🤫😉)
100
Alex @alexpellancheng.bsky.social · 11/04/2025
Routine WGS would have been insanity in 2020 💰💰💰But today? Prices can be as low as 0$ per GB. www.genengnews.com/topics/omics...
genengnews.com
Ultima Genomics Gives Away Sequencing for Free. Literally.
Ultima Genomics announces that it will provide three trillion DNA sequencing reads free of charge to researchers across the United States and Canada.
100
Alex @alexpellancheng.bsky.social · 11/04/2025
The concept of plasma whole genome sequencing (WGS) for cancer monitoring makes a ton of sense: one workflow, no panels, ultrasensitive detection www.nature.com/articles/s41...
nature.com
Genome-wide cell-free DNA mutational integration enables ultra-sensitive cancer monitoring - Nature Medicine
A new approach for whole-genome sequencing of plasma circulating tumor DNA allows for dynamic monitoring of disease burden and ultra-sensitive detection of minimal residual disease.
110
Alex @alexpellancheng.bsky.social · 11/04/2025
What happens when sequencing costs go ⏬ ? Imagination and new opportunities go ⏫ @landau.bsky.social Let's look at what you can do when you perform deep WGS on cfDNA for cancer detection. Our recent work with the @UltimaGenomics platform 🧵👇 Lets goooo!! rdcu.be/ehkUb
rdcu.be
Error-corrected flow-based sequencing at whole-genome scale and its application to circulating cell-free DNA profiling
Nature Methods - This work integrates duplex sequencing with cost-effective Ultima sequencing to enhance the accuracy of whole-genome circulating cell-free DNA profiling.
3117