This study builds on PACIFIC, our computational method for detecting clinically important multi-omics interactions (aacrjournals.org/mcr/article/...). Here, we extend this interaction-based framework to discovery of prognostic signatures defined by pairs of genomic alterations. [4/4]
These PGIs refined prognostic stratification and were linked to distinct transcriptomic programs, while also highlighting candidate genes within recurrent copy-number regions and supported functional dependencies. [3/4]
Using genomic and clinical data from nearly 10,000 primary tumors, we identified 57 prognostic genomic interactions (PGIs): pairs of alterations whose joint status was associated with patient outcome beyond either alteration alone. [2/4]
New preprint from our lab out "Pairwise genomic alterations identify prognostic tumor states in multiple cancer types". Most genomic models of cancer prognosis focus on single alterations. Here, we asked what can be learned from combinations of events [1/4] doi.org/10.64898/202...
Also, alterations in DNA damage response genes (eg BRCA2) were associated with increased CTCF site mutation enrichment following radiotherapy. The implicated CTCF sites are constitutively active across human tissues, extending treatment-associated mutagenesis to regulatory genome architecture [3/3].
Analysing 4870 metastatic tumor whole genomes, we found that radiotherapy and trifluridine exposure in metastatic colorectal cancer associated with increased mutation enrichment at CTCF binding sites. Effects were strongest at motif-containing sites, low-expression or late-replicating contexts [2/3]
New preprint from our lab "Therapy-associated mutagenesis at CTCF binding sites is shaped by chromatin context and DNA repair capacity" led by @cclkevin.bsky.social. This work asks how genotoxic cancer therapies shape mutations at regulatory elements in cancer genomes [1/3] doi.org/10.64898/202...
We are very happy to see our study finally appear online @nature.com! This has been work of nearly 10 years in collaboration with the National Institute of Genome Medicine 🇲🇽, the National Cancer Institute 🇲🇽, the @sangerinstitute.bsky.social and others ⬇️
www.nature.com/articles/s41...
rwSNVs are enriched in cancer driver genes and pathways. For example, UV-associated rwSNVs at BRAF V600E are predicted to generate a PLK1 phosphorylation motif, adding a new layer to canonical MAPK activation. Congrats to our PhD student @jigsmishra.bsky.social on leading this study! @oicr.on.ca
Analyzing >11,000 cancer genomes and 144 classes of SLiMs, we identify motif-rewiring SNVs (rwSNVs) that create or disrupt signaling motifs or remove phosphoresidues. APOBEC, methylcytosine deamination, and UV light emerge as major drivers of rwSNVs.
Somatic mutational signatures describe where mutations come from 🧬. But do they shape how proteins function? In our new preprint, we show that mutational processes can systematically rewire cellular signaling networks by altering short linear motifs (SLiMs). Preprint: www.biorxiv.org/content/10.6...
First I'm hearing of DOPRA, love it! "Denial of peer review attack" concept by @lpachter.bsky.social
Finding the right balance of persistence and letting-it-go
Graduate school interview season is approaching.
After ~12 years of interviewing PhD and MD/PhD applicants, I’ve noticed some common interview mistakes that hold otherwise strong candidates back...
#GraduateSchool #PhDLife #MDPhD #GradSchoolTips #AcademicBluesky
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🧬 Protein that unties tangled DNA linked to hotspots of cancer mutations: Research from @reimand.bsky.social and his collaborators associated a chemotherapy-related cellular process with genetic mutations and used it to identify novel cancer driver alterations. https://bit.ly/4iMcV5B
Thank you: collaborators @wilson-md.bsky.social &lab for epigenomics experiments, topoisomerase insights; @danielschramek.bsky.social &lab for functional genomics; @MamathaBhat3 &lab for liver cancer expertise. For funding @oicr.on.ca CIHR TFRI, and to patients for tumor samples in PCAWG, HMF. [7/7]
Overall, the study reveals how genome structure, DNA repair, and even chemotherapy shape where cancers begin -- and opens the door to finding many more hidden regulatory drivers. [6/7]
Using CRISPR in mouse models and human cells, we showed that mutations at this RMRP element can accelerate tumour growth, confirming it as a true non-coding driver. [5/7]
Focusing on these regions helped us discover new non-coding driver mutations, including a key regulatory hotspot at the RMRP non-coding RNA gene. [4/7]
These mutation-prone sites often sit at busy regulatory hubs where the genome folds and loops, and might affect gene regulatory circuits. They’re also might be sensitive to common chemotherapy drugs that inadvertently target TOP2B. [3/7]
By combining TOP2B maps with 6,500 whole cancer genomes, we found that this enzyme marks genomic fault lines -- places where small mutations (SNVs, indels) and structural variants (CNAs, translocations) tend to pile up. [2/7]
⚠️New study: we mapped DNA-binding of topoisomerase TOP2B in cancer, uncovering surprising hotspots of DNA damage. TOP2B, normally essential for DNA stress relief, can act as a double-edged sword. co-led by @LiisUuskula @ChristianLee, out now @natcomms.nature.com www.nature.com/articles/s41... [1/7]
Better DNA repair machinery protects one of the largest mammals from cancer: www.nature.com/articles/s41... 🐋
Fantastic opportunity at The Hospital for Sick Children. Please repost. www.nature.com/naturecareer...
made my first meme to celebrate the never-boring pathway to publication. #PIlyfe #openaccess
Excited to see this study led by Nick Min & Xi Huang published this week and grateful for a decade of collaborations : www.nature.com/articles/s41...
The PACIFIC method is available on github: github.com/reimandlab/P...
Congrats to our PhD student Masroor Bayati for his first-author publication out this week. We developed a computational method to map synergistic interactions in omics datasets and studied prognostic signals of co-occurring cancer driver alterations and TME features. aacrjournals.org/mcr/article/...
