Project description:Background Cancer is one of the leading causes for the morbidity and mortality worldwide. Although substantial studies have been conducted theoretically and experimentally in recent years, it is still a challenge to explore the mechanisms of cancer initiation and progression. The investigation for these problems is very important for the diagnosis of cancer diseases and development of treatment schemes. Results To accurately describe the process of cancer initiation, we propose a new concept of gene initial mutation rate based on our recently designed mathematical model using the non-constant mutation rate. Unlike the widely-used average gene mutation rate that depends on the number of mutations, the gene initial mutation rate can be used to describe the initiation process of a single patient. In addition, we propose the instantaneous tumour doubling time that is a continuous function of time based on the non-constant mutation rate. Our proposed concepts are supported by the clinic data of seven patients with advanced pancreatic cancer. The regression results suggest that, compared with the average mutation rate, the estimated initial mutation rate has a larger value of correlation coefficient with the patient survival time. We also provide the estimated tumour size of these seven patients over time. Conclusions The proposed concepts can be used to describe the cancer initiation and progression for different patients more accurately. Since a quantitative understanding of cancer progression is important for clinical treatment, our proposed model and calculated results may provide insights into the development of treatment schemes and also have other clinic implications.

2024-09-02 | BIOMD0000000915 | BioModels

Quantification of basal RNA mutation rate in the repRNA-v4 EGFP region

Project description:REPLACE was engineered from an orthogonal alphaviral RNA replication system. It generates a large, continuously diversified library of replicative RNAs through a replicase-limited mode of replication and inducible mutagenesis. We analyzed the mutation frequency at Day0 (IVT RNA), Day1, Day3, Day7, Day14, Day21 and DNA plasmid to estimate the RNA mutation rate. This data was used to guide the construction of RNA mutant libraries.

2024-09-30 | GSE271880 | GEO

Great Ape Mutation Rates

Project description:Great Ape Trio de novo Mutation Rate estimation

| PRJEB29710 | ENA

Metastatic adrenocortical carcinoma displays higher mutation rate and tumor heterogeneity than primary tumors

Project description:Metastatic adrenocortical carcinoma displays higher mutation rate and tumor heterogeneity than primary tumors

| PRJNA484072 | ENA

Metastatic adrenocortical carcinoma displays higher mutation rate and tumor heterogeneity than primary tumors

Project description:Metastatic adrenocortical carcinoma displays higher mutation rate and tumor heterogeneity than primary tumors

| PRJNA484071 | ENA

A single gene mutation underpins metabolic adaptation and acquisition of filamentous competence in the emerging fungal pathogen Candida auris

Project description:<p>Filamentous cell growth is a vital property of fungal pathogens. The mechanisms of filamentation in the emerging multidrug-resistant fungal pathogen Candida auris are poorly understood. Here, we show that exposure of C. auris to glycerol triggers a rod-like filamentation-competent (RL-FC) phenotype, which forms elongated filamentous cells after a prolonged culture period. Whole-genome sequencing analysis reveals that all RL-FC isolates harbor a mutation in the C2H2 zinc finger transcription factor-encoding gene <em>GFC1</em> (Gfc1 variants). Deletion of GFC1 leads to an RL-FC phenotype similar to that observed in Gfc1 variants. We further demonstrate that GFC1 mutation causes enhanced fatty acid β-oxidation metabolism and thereby promotes RL-FC/filamentous growth. This regulation is achieved through a Multiple Carbon source Utilizer (Mcu1)-dependent mechanism. Interestingly, both the evolved RL-FC isolates and the gfc1Δ mutant exhibit an enhanced ability to colonize the skin. Our results reveal that glycerol-mediated GFC1 mutations are beneficial during C. auris skin colonization and infection.</p>

2024-07-04 | MTBLS9053 | MetaboLights

Evaluation of mutation rate in plasmid and virus

Project description:We report the mutation profile of measles F gene by saturating mutagenesis.

2020-12-09 | GSE146767 | GEO