Anna Nam

Physician-scientist & molecular hematopathologist at Weill Cornell Medicine

[Anna Nam @AnnaEnim]

Pls RT: The Nam Lab at WCM is recruiting post-doctoral fellows to join the growing team!

If you're interested in deciphering blood cancers through advanced single-cell technologies, please DM me and visit our website https://t.co/vzml2Llu85 to learn more.

[Caleb Lareau @CalebLareau]

We’re unwrapping a new method today @MSKCancerCenter!

Led by @SydneyBlattman, @NabihMaslah, @AustinAVarela, Ronan Chaligne and @dana_peer, plus colleagues at @10xGenomics, we’re delighted to share Genotyping In Fixed Transcriptomes (GIFT):

https://t.co/n62R2flHuc

1/n

[Luciano Martelotto 🛠🧬💻🇦🇺 @LGMartelotto]

What a great week for Gap Filling techs for genotyping transcriptomes!!!

Amazing work from the one and only super talented teams of @dana_peer, Ronan Chaligne and @CalebLareau

Genotyping in fixed transcriptomes resolves clonal heterogeneity via single-cell sequencing.

https://t.co/D5QWxVos0E

[Luciano Martelotto 🛠🧬💻🇦🇺 @LGMartelotto]

We GoT a Filling…uuuuhoooo

𝗧𝗮𝗿𝗴𝗲𝘁𝗲𝗱 𝘀𝗲𝗾𝘂𝗲𝗻𝗰𝗶𝗻𝗴 𝗼𝗳 𝗺𝘂𝘁𝗮𝘁𝗶𝗼𝗻𝘀 𝘃𝗶𝗮 𝗥𝗡𝗔-𝘁𝗲𝗺𝗽𝗹𝗮𝘁𝗲𝗱 𝗴𝗮𝗽 𝗳𝗶𝗹𝗹𝗶𝗻𝗴 𝗼𝗳 𝗼𝗹𝗶𝗴𝗼𝗻𝘂𝗰𝗹𝗲𝗼𝘁𝗶𝗱𝗲𝘀 𝗳𝗼𝗿 𝘀𝗶𝗻𝗴𝗹𝗲-𝗰𝗲𝗹𝗹 𝗥𝗡𝗔-𝘀𝗲𝗾

Download here: https://t.co/CRAFwIFNqY…

1/ 🧬 New preprint! We developed GoT-Multi-Gap — a method to detect expressed mutations in single cells without needing to know the variant sequence in advance.
Built on RNA-templated gap filling.

Thread 🧵👇

2/ The problem: detecting mutations in scRNA-seq is hard. Coverage is sparse, and capture methods lose sensitivity the farther a mutation sits from the transcript end. Ligation-based approaches (like our earlier GoT-Multi) require allele-specific probes — limiting scalability.
3/ Our solution: exploit the dual enzymatic activity of Bst FL polymerase. It reverse-transcribes across a gap between flanking probes on mRNA, then uses nick translation to activate the downstream probe for ligation. No allele-specific design needed.
4/ The trick: the downstream probe starts with a 5’-OH (ligation-incompetent). After Bst fills the gap and nicks the terminus, a 5’-phosphate is exposed → SplintR ligase seals the nick. The mutation sequence gets written into the product automatically.
5/ We validated the chemistry in situ with padlock probes + rolling circle amplification on 18S rRNA. Key insight: exonuclease-resistant backbone mods on the downstream probe fine-tune polymerase vs. nick-translation competition, boosting efficiency.
6/ We then built this into 10x Flex (GoT-Multi-Gap). Three cell lines (MCF-7, SK-BR-3, LnCAP), 61 SNVs targeted across a range of gap sizes. Critically — the gap-filling step didn’t perturb Flex performance. UMI counts, gene counts, correlations all preserved.
7/ Results: among targets with ≥10 genotyped cells, mutant calls showed 80-100% specificity to the expected cell line. The main driver of detection sensitivity? Target transcript abundance (Pearson R=0.37, P<0.01).
8/ What didn’t matter much: gap length (4-12 bp), mutation position within the gap, and probe GC content (within the 44-72% window). The assay captures variants across the full gap with comparable sensitivity.
9/ Bottom line: GoT-Multi-Gap enables simultaneous whole-transcriptome + multiplexed mutation profiling from the same single cell, without prior knowledge of variant identity. Scalable, compatible with existing workflows, and ready for complex mutational landscapes.
10/ Huge thanks to all authors and absolute special shout out to @MircaSaurty, @lee_hower and @Kellieiswise and the incredible team @WeillCornell and @scilifelab.

[Luciano Martelotto 🛠🧬💻🇦🇺 @LGMartelotto]

Why so serious? 🃏

Marco Grillo, @AnnaEnim and yours truly 𝗚𝗼𝗧 𝗮 𝗙𝗶𝗹𝗹𝗶𝗻𝗴 that will make you happy 😃

No more limitations. Maximum flexibility.

Something is coming. Stay tuned.

#singlecellwithaplus

[Anna Nam @AnnaEnim]

An amazing collaboration with the brilliant Marco Grillo and @LGMartelotto. Led by our super stars Mirca Saurty-Seerunghen and Hower Lee. Please check out our new method - GoT-Multi-Gap - out on biorxiv and summarized below!

[Luciano Martelotto 🛠🧬💻🇦🇺 @LGMartelotto]

Awesome preview of our GoT-Multi by @bloodgenes and @JGudera!

—&gt; @AnnaEnim GoT Queen!

Charting clonal evolution and behavior with GoT-Multi: Cell Genomics https://t.co/VaIt6pYI5E

[Anna Nam @AnnaEnim]

@bloodgenes @CellGenomics @JGudera @LGMartelotto Thank you so much for the insightful preview, Vijay!

[Vijay Sankaran @bloodgenes]

Enjoyed writing this Preview in @CellGenomics with @JGudera on GoT-Multi 🪄
A powerful #singlecell approach from the teams of @AnnaEnim and @LGMartelotto
Preview: https://t.co/SXw21jzaHK
Paper: https://t.co/6avzi5lYRs

[Genetic Engineering & Biotechnology News @GENbio]

Leukemia Progression Mapped by New Multi-Omics Tool, GoT-Multi

GoT-Multi maps somatic #genotypes and transcriptomes in single cancer cells, revealing more on clonal evolution and therapy resistance
@AnnaEnim @WeillCornell
#leukemia #multiomics
https://t.co/eAxXh6hZwc

[Anna Nam @AnnaEnim]

@PapapetrouMDPhD @CellGenomics @LGMartelotto Thank you so much, Eirini!!

[Anna Nam @AnnaEnim]

Excited to introduce GoT-Multi, out at @CellGenomics: https://t.co/vV0p7EC9Df! Developed together with the single cell wizard @LGMartelotto, GoT-Multi is a next gen single cell multi-omics - multiplexed genotyping in transcriptomes compatible with FFPE samples.

[Anna Nam @AnnaEnim]

@bloodgenes @CellGenomics @LGMartelotto Thank you so much, Vijay!!

[Weill Cornell Medicine Pathology @WCMCPathology]

“This technology gives us new power to answer important questions about how #cancers evolve, from pre-cancerous #neoplastic outgrowths to transformation into malignancy and resistance,” Dr. Anna Nam (@AnnaEnim)from @WCMCPathology and the @WCMEnglanderIPM

https://t.co/SMAWp01mIg

[Anna Nam @AnnaEnim]

@LGMartelotto Perfectly articulated, as always!!! Could not agree more about this amazing collaboration! I owe you a visit for sure… Looking forward to many years of collaboration and friendship ahead!

[Anna Nam @AnnaEnim]

RT @LGMartelotto: YES!!! It’s out! 🔥

One of the most amazingly beautiful collaborations.

I’ve admired @AnnaEnim since her original GoT -…

[Anna Nam @AnnaEnim]

@AlejoFraticelli @CellGenomics @LGMartelotto @JudeNicho @NIH @BWFUND Thank you so much @AlejoFraticelli! Really appreciated all your helpful feedback!

[Anna Nam @AnnaEnim]

@LGMartelotto @WCMCPathology @pewtrusts Thank you, Lu!!

[Anna Nam @AnnaEnim]

@AbdelWahablab @TaylorJ_MD @WCMCPathology @pewtrusts Thank you so much for your support, Omar!!

[Anna Nam @AnnaEnim]

@TzelepisLab @WCMCPathology @pewtrusts Thank you so much! It was great to meet you back in May!