New Method Uses DNA Methylation Patterns to Trace Colorectal Tumor Growth History
Researchers have developed a mechanistic computational model that uses fluctuating DNA methylation patterns to reconstruct how colorectal tumors grow and evolve over time. The model was applied to multi-region tissue samples from 10 resected colorectal tumors, including adenomas and carcinomas at various stages. The findings offer a new window into tumor growth dynamics without requiring longitudinal biopsies, with potential applications to other solid tumor types.
A team of researchers has introduced a computational framework capable of inferring colorectal tumor growth history from DNA methylation data collected across multiple regions of resected tumors. The model tracks heritable methylation marks as a tumor expands from a single gland to a large mass, and uses an ABC-SMC (Approximate Bayesian Computation Sequential Monte Carlo) inference workflow to estimate key growth parameters. Applied to 10 colorectal tumors — three adenomas and seven carcinomas of varying sizes and clinical stages — the framework revealed that intratumor methylation diversity arises primarily from gland fission rather than cell turnover within individual glands. Gland fission rates varied up to eightfold between patients, accounting for much of the observed differences in intratumor diversity, alongside variation in methylation and demethylation rates. The inter-gland divergence patterns were found to be consistent with neutral evolution and suggest a cancer stem cell fraction of approximately 1%. The authors propose that the method could be adapted beyond colorectal cancer to other solid tumor types.
What's missing
As a preprint posted on bioRxiv, this work has not yet undergone formal peer review, and its findings should be interpreted with that caveat in mind. The study is limited to 10 patients, which constrains statistical power and generalizability. It is also unclear how well the framework would perform on tumors with different architectural or epigenetic properties outside the colorectal context.
What different sources said
- bioRxivCenter
Fluctuating DNA methylation sites encode colorectal tumour growth history
Related
Gut Bacteria Enzyme Found to Break Down Heat-Processed Food Compounds, Producing Novel Biogenic Amines
Researchers have discovered that an enzyme in common gut bacteria can degrade N-epsilon-carboxymethyllysine (CML), a compound formed during thermal food processing, producing previously unknown biogenic amines. The enzyme, ornithine decarboxylase SpeC from enterobacteria, acts on CML and related modified lysine derivatives through a low-level 'underground' catalytic activity. This finding suggests a previously unrecognized communication axis between thermally processed dietary compounds and gut microbial physiology, with potential implications for host health.
Full-Length Gene Sequencing Reveals Two Distinct Bacterial Communities in Black-Legged Ticks Expanding Into Canada
Researchers used Oxford Nanopore full-length 16S rRNA gene sequencing to characterize the microbiome of Ixodes scapularis black-legged ticks collected in Nova Scotia, Canada, distinguishing between tick-adapted bacteria and environmentally acquired bacteria. The study comes as I. scapularis — the primary vector of Lyme disease — is rapidly expanding northward into Canada due to climate change. The findings suggest that environmentally derived bacteria in tick microbiomes are not mere contamination, which has implications for how tick microbiome data is collected and interpreted across surveillance studies.
Study Identifies Metabolic Link Between Cell Envelope Stress and Biofilm Formation in Bacteria
Researchers have discovered that the metabolite acetyl-CoA directly inhibits enzymes that degrade the bacterial signaling molecule c-di-GMP, connecting cell envelope biosynthesis stress to biofilm formation in Pseudomonas aeruginosa. The study found that sub-inhibitory concentrations of antibiotics targeting early peptidoglycan biosynthesis — but not other antibiotic classes — elevate c-di-GMP levels by reducing phosphodiesterase activity, with acetyl-CoA competing for the enzyme active site. Because the relevant enzyme domain is broadly conserved across bacterial species, this checkpoint mechanism may be widespread and could have implications for understanding antibiotic-induced biofilm responses.