Biology subjects

Nunes, L.

Publications and source records attributed to Nunes, L..

4 recordsLinked to original sources

bioRxiv2026

Epigenetic reprogramming by promoter hypomethylation is linked to aberrant gene expression and transcriptomic plasticity in colorectal cancer

Colorectal cancer (CRC) has high phenotypic plasticity, but regulatory mechanisms of aberrant cell states are not well described. We investigated DNA methylation-based regulation of cancer cell-intrinsic transcriptomic heterogeneity in 1,183 multiregional primary tumor samples, liver metastases and tumor organoids. Most genes with strong methylation-transcriptomic association reflected canonical promoter hypermethylation and expression repression related to the CpG island methylator phenotype (CIMP). However, promoter hypomethylation and overexpression of APOLD1 and ELF5 identified two largely non-overlapping subgroups of canonical CIMP-negative CRCs enriched with stem-like and transit-amplifying cell states. APOLD1 tumors were further highly proliferative while ELF5 tumors were slow-cycling and associated with good survival in early-stage disease. Target genes showed patient-specific expression changes in matched primary-metastasis samples, and ELF5 aberrant metastases showed ex vivo sensitivity to putative targeting of stem cells by PI3K/mTOR inhibition, fetal de-differentiation and transition into non-canonical intestinal states. This implicates focal promoter hypomethylation in phenotypic plasticity in CRC metastasis.

genomics↗

bioRxiv2026

Phenomic selection enables nursery screening for field performance in maize and pea

Due to economical constraints, breeding programs eliminate most selection candidates at early stages, before their productivity can be evaluated in field trials. Genomic selection partially overcomes this limitation by enabling early prediction of field performance, but its implementation requires large-scale recurrent genotyping that remains inaccessible for many species and breeding programs. Phenomic selection offers a promising alternative by replacing genotyping with inexpensive high-dimensional phenotyping data. However, previous applications have focused on predicting genotypes already evaluated in field trials. We investigated whether phenomic data acquired by unoccupied aerial vehicles (UAVs) from nursery-grown genotypes can be used to predict their performance in field trials. We validated this nursery-screening approach in maize and pea, two species with contrasting biology and canopy structures, supporting its potential transferability to other species. In the most challenging scenarios, average accuracies for yield-related traits were between 0.36 for maize and 0.40 for pea. Simulations indicated that these accuracies can support substantial nursery culling while limiting the risk of discarding superior genotypes. This proof of concept demonstrates that UAV-based phenomic selection can predict the field performance of nursery-grown genotypes without genotyping the selection candidates.

genetics↗

bioRxiv2023

Recurring EPHB1 mutations in human cancers alter receptor signalling and compartmentalisation of colorectal cancer cells

Ephrin (EPH) receptors have been implicated in tumorigenesis and metastasis, but the functional understanding of mutations observed in human cancers is limited. We previously demonstrated reduced cell compartmentalisation for somatic EPHB1 mutations found in metastatic colorectal cancer cases. We, therefore, integrated pan-cancer and pan-EPH mutational data to prioritise recurrent EPHB1 mutations for functional studies to understand their contribution to cancer development and metastasis. Here, 79,151 somatic mutations in 9,898 samples of 33 different tumour types were analysed to find 3D-mutated cluster pairs and recurring hotspot mutations in EPH receptors. From these, 15 recurring EPHB1 mutations were stably expressed in colorectal cancer cells. Whereas the ligand-binding domain mutations C61Y, R90C, and R170W, the fibronectin domain mutation R351L, and the kinase domain mutation D762N displayed reduced to strongly compromised cell compartmentalisation, the kinase domain mutations R743W and G821R enhanced this phenotype. While mutants with reduced compartmentalisation also had reduced ligand induced receptor phosphorylation, the enhanced compartmentalisation was not linked to receptor phosphorylation level. Phosphoproteome mapping pinpointed the PI3K pathway and PIK3C2B phosphorylation in cells harbouring mutants with reduced compartmentalisation. This is the first integrative study of pan-cancer EPH receptor mutations followed by in vitro validation, a robust way to identify cancer-causing mutations.

cancer biology↗

bioRxiv2020

European Primary Forest Database (EPFD) v2.0

Primary forests are scarce in Europe and continue to disappear at an alarming rate. Despite these losses, we know little about where such forests still occur. Here, we present an updated geodatabase and map of Europes known primary forests. Our geodatabase harmonizes 48 different datasets of primary forests, and contains 18,411 individual patches (41.1 Mha) spread across 33 countries. When available, we provide information on each patch (name, location, naturalness, extent and dominant tree species) and the surrounding landscape (biogeographical regions, protection status, potential natural vegetation, current forest extent). To assess the robustness of our geodatabase, we checked each patch for forest disturbance events using Landsat satellite-image time series (1985-2018). We estimate that 94% of the patches in our database did not experience significant disturbances that would alter their primary forest status in the last 30 year. Our database is the most comprehensive dataset on primary forests in Europe, and will be useful for biogeographic and ecological studies, and conservation planning to safeguard these unique forests.

ecology↗