Biology subjects

Bermudez-Guzman, L.

Publications and source records attributed to Bermudez-Guzman, L..

3 recordsLinked to original sources

bioRxiv2026

Prevalence of Colorectal Cancer Molecular Profiles Is Not Captured by a Single Age Threshold

Early- and average-onset colorectal cancer (CRC) are separated at age 50, but whether this defines a biological threshold remains unclear. To clarify this, we identified molecular profiles in nine harmonised cBioPortal CRC cohorts (4,609 patients) by fitting Bernoulli mixture models to 31 repair-state, genomic-burden and gene-alteration features, excluding age, sex and tumour site, and compared their prevalence using <50/[≥]50 and decade-resolved groups. Four profiles captured conventional/CIN-like (P1), intermediate MSS (P2), KRAS/PI3K/APC-rich (P3) and hypermutated/MSI-high (P4) states along a left-to-right anatomical gradient. Although molecular identities remained stable, profile prevalence followed non-linear P1/P4 and opposing linear P2/P3 age trajectories. Profile prevalence patterns did not follow age distance: profile composition at 30-39 differed from 50-59 but not clearly from 40-49 or 60-69. The age-50 threshold captured only 17.8% of decade-resolved deviance, whereas the optimal age-70 cut-off retained only 51.3%. Validation in 2,235 non-overlapping MSK-IMPACT patients (2,134 age-evaluable) reproduced molecular-feature patterns (r=0.96-1.00), age trajectories (r=0.90) and limited binary-threshold performance: age 50 and the optimal age-75 cut-off retained 6.2% and 49.4%, respectively. Thus, age reorganises the prevalence of shared CRC states rather than defining a biological threshold at age 50.

cancer biology↗

bioRxiv2020

Mutational Survivorship Bias: The case of PNKP

The molecular function of a protein relies on its structure. Understanding how mutations alter structure and function in multi-domain proteins, is key to elucidate how a pathological phenotype is generated. However, one may fall into the logical bias of assessing protein damage only based on the mutations that are viable (survivorship bias), which can lead to partial conclusions. This is the case of PNKP, an important nuclear and mitochondrial DNA repair enzyme with kinase and phosphatase function. Most mutations in PNKP are confined to the kinase domain, leading to a pathological spectrum of three apparently distinct clinical entities. Since proteins and domains may have a different tolerance to disease causing mutations, we evaluated whether mutations in PNKP are under survivorship bias. Even when all mutations in the kinase domain are deleterious, we found a mayor mutation tolerability landscape in terms of survival. Instead, the phosphatase domain is less tolerant due to its low mutation rates, higher degree of sequence conservation, lower dN/dS ratios, and more disease-propensity hotspots. Thus, in multi-domain proteins, we propose the term "Walds domain" for those who are not apparently more associated with disease, but that are less resistant to mutations in terms of survival. Together, our results support previous experimental evidence that demonstrated that the phosphatase domain is functionally more necessary and relevant for DNA repair, especially in the context of the development of the central nervous system. Thus, this bias should be taken into account when analyzing the mutational landscape in protein structure, function, and finally in disease.

molecular biology↗

bioRxiv2019

Microplastic ingestion by a herring Opisthonema sp., in the Pacific coast of Costa Rica

Despite there is a growing interest in studying the presence and effects of microplastics (MP) in fishes and other aquatic species, knowledge is still limited in tropical areas. In this study, we examined the presence of MP in the gastrointestinal content of 30 filter feeders of thread herring, Opisthonema complex (Clupeiformes: Clupeidae) from the Central Pacific coast of Costa Rica. We detected the presence of MP in 100% of the individuals with an average of 36.7 pieces per fish, of which 79.5% were fibers and 20.5% particles. To our knowledge, this is the first study in Costa Rica that demonstrates the presence of MP in planktivorous fishes. The effects of microplastics ingestion by O. libertate and its transit through aquatic food webs should be studied in greater detail, with greater number of sampling points at different times of the year. However, our work confirms that contamination by microplastics is having direct effects on the marine life of Costa Rica.\n\nCapsuleThis is the first multidisciplinary study in Costa Rica demonstrating the presence and nature of microplastics in the digestive tract of planktivorous fish.

zoology↗