Biology subjects

Di Genova, A.

Publications and source records attributed to Di Genova, A..

13 recordsLinked to original sources

bioRxiv2026

A multi-omic, spatial, and whole-slide image dataset of lung neuroendocrine tumours from the lungNENomics cohort

Lung neuroendocrine tumours (lung NETs) are rare neoplasms comprising approximately 2% of lung cancers. Recent studies have identified distinct molecular groups based on transcriptome and methylome data, but genomic and morphological features remain underexplored due to limited whole-genome and imaging data. We have generated the largest multi-omic dataset of lung NETs to date (201 participants, for a total of n = 294 tumours), including RNA sequencing, EPIC 850K methylation arrays, and whole-genome sequencing. This multiomic dataset also include multi-regional whole-genome sequencing for 41 participants, allowing for the quantification of intra-tumoural heterogeneity. We additionally generated spatial proteomics (64 participants), spatial transcriptomics (4 participants) and whole-slide histopathology images for 212 cases. This dataset enables a comprehensive characterization of lung NET molecular groups and the identification of group-specific morphological features using deep learning algorithms. All quality control analyses, processed data, and scripts are provided to ensure reproducibility. This dataset is available as a basis for further molecular and morphological analysis of lung NETs, and for future research on multi-scale integration.

bioinformatics↗

bioRxiv2026

Accurate haplotype-resolved de novo assembly of human genomes with RFhap

Haplotype-resolved de novo assemblies enable genome-wide separation of maternal and paternal variation, improving the interpretation of complex variants relevant to human disease. Trio-aware assemblers such as Hifiasm-Trio leverage parental short reads by deriving parent-specific k-mers to guide phasing within the long-read assembly graph; however, fixed k-mer length and heuristics cannot be optimal in the presence of sequencing errors and graph complexity in repetitive regions, contributing to phasing errors and reduced haplotype-resolved contiguity. Here we present RFhap, a trio-based long-read phasing method that integrates multi-k-mer parent-specific markers with an alignment-free k-mer lookup engine and a random forest classifier to assign long reads to maternal, paternal, or unknown haplotypes prior to de novo assembly. We benchmarked RFhap on four human trio datasets from the Human Pangenome project spanning two ONT chemistries (R10.4 and R9.4.1). Using Merqury to evaluate downstream assemblies, RFhap nearly doubled corrected haplotype NG50 (mean 24.3 Mb vs 13.1 Mb) and halved switch error rates (mean 0.111% vs 0.236%) relative to Hifiasm-Trio, while remaining competitive in consensus QV and parental k-mer completeness. Consistent with improved phasing, RFhap reduced long-switch errors by [~]3-fold across datasets, particularly within interspersed repeats. Together, these results demonstrate that RFhap improves phasing accuracy from standard trio data, representing a step toward accurate and automated diploid human de novo assembly from long reads.

bioinformatics↗

bioRxiv2026

Ultra-deep sequencing reveals intra-host diversity and co-infection-driven evolution of SARS-CoV-2

As COVID-19 enters an endemic phase, SARS-CoV-2 continues to diversify under ongoing immune pressure, with Omicron sublineages and episodic emergent variants sustaining reinfections worldwide. Intra-host evolution represents the earliest stage of this diversification, yet remains undercharacterized, particularly in regions with limited genomic surveillance. Here, we conducted high-throughput sequencing on 96 nasopharyngeal swab samples from Chilean individuals (2020-2022), achieving an average per-base genome coverage of [~]60,000x across the viral genome. This ultra-deep sequencing coverage enabled the identification of intra-host single-nucleotide variants (iSNVs) and co-infection events with high sensitivity and accuracy. Co-infections, especially with Omicron, significantly increased iSNV frequency and recombination, driving viral diversity. Evolutionary analysis based on the non-synonymous to synonymous ratio (dN/dS) shows that Omicron is under extensive purifying selection (global dN/dS [~] 0.55). However, Omicron co-infection cases exhibited higher dN/dS ratios ([~]0.58), suggesting a lower level of purifying selection and increased genetic diversity. Notably, the Spike gene showed dN/dS ratios indicative of positive selection (dN/dS > 1), which are more pronounced in co-infection cases than in Omicron alone. This suggests that co-infections are providing the substrate for the emergence of new variants with enhanced transmissibility and immune evasion capabilities. Together, these findings demonstrate that ultra-deep sequencing is crucial for mapping the evolutionary forces driving SARS-CoV-2 intra-host adaptation and the emergence of new variants.

genetics↗

bioRxiv2025

Effects of Willow and Pine tree growth in bacterial abundance, interactions and metabolic profile in a copper mine tailing

The Cauquenes tailings is one of the largest mine tailings in Chile and represents a significant environmental hazard due to its high copper levels and acidic pH. However, there is evidence of willow and pine tree growth in these terrains, which is unexpected given the extreme conditions of this environment. Considering the importance of plants in restoration strategies, the objective of this study was to analyze the effect that willow and pine growth have on the heavy metal contents of their surrounding soil, and the abundance, interaction, metabolic profile and assembly of the bacterial community. In the Cauquenes tailing, we collected samples from willow and pine vegetated soils as well as the surrounding non-vegetated soils. We analyzed characteristics such as heavy metal concentrations and pH levels in all sampled soils, and in tree leaves and roots. Vegetated sites exhibited lower copper levels and a neutral pH, while both tree species accumulated heavy metals in their tissues. We also determined bacterial abundance in all soil samples, and co-occurrence networks were constructed to assess bacterial interactions. Both trees promoted a higher abundance of Proteobacteria and had networks with higher modularity compared to non-vegetated soils. Finally, we estimated the metabolic profile of the bacterial community using PICRUSt 2 analysis and determined carbon source utilization with BioLog Ecoplates. PICRUSt 2 predicted higher metabolic activity in vegetated soils, and BioLog Ecoplate analysis revealed the utilization of a greater number of carbon sources. The microbial communities from vegetated soils were assembled in a deterministic manner, while the community from non-vegetated soils were stochastically assembled. In conclusion, tree growth mitigated the extreme conditions of the tailing and promoted a more active and healthier bacterial community. HighlightsO_LIWillow and pine tree can grow and mitigate toxic metal conditions in the tailings C_LIO_LIBoth trees provoked a shift in bacterial abundance and interaction network C_LIO_LIThe provoked shift was tree-dependent C_LIO_LIMicrobial activity was higher in vegetated soils C_LI

microbiology↗

bioRxiv2024

Photosynthetic and Genetic Adaptations Underpinning the Resilience of Cistanthe longiscapa in the Atacama Desert

O_LIThe Atacama Desert is one of the most hostile environments for life. However, the plant species Cistanthe longiscapa (C. longiscapa) completes its life cycle in the Atacama Desert after sporadic rainfall. C_LIO_LIPhysiological analyses under controlled environmental conditions revealed superior photosynthetic performance, better light acclimation mechanisms, and larger accumulation of photosystem II in C. longiscapa compared to its mesophilic sister species. C_LIO_LIC. longiscapa shows evolutionary expansions in gene families related to DNA repair, photosynthesis, and protein homeostasis. In addition, we observed substantial gene duplication and polymorphic variations between coastal and inland populations in the Atacama Desert. Finally, our assembled mitochondrial genome provides genetic information for all DNA-containing compartments of C. longiscapa. C_LIO_LIDiurnal oscillations of malic acid and time-resolved transcriptome analyses of plants harvested in the Atacama Desert indicate that C. longiscapa engages in CAM metabolism. We observed significant differences in transcripts encoding plastid-localized proteins, including those involved in carbon metabolism, light harvesting, and photoprotection, highlighting the critical role of chloroplasts in the adaptation of C. longiscapa to the Atacama Desert. C_LIO_LIOur study provides physiological and genetic evidence for the adaptations of C. longiscapa and advances our understanding of how plants can cope with extreme environmental conditions. C_LI

plant biology↗

bioRxiv2024

Profiling extremophile bacterial communities recovered from a mining tailing against soil ecosystems through comparative genome-resolved metagenomics and evolutionary analysis

Microbial communities inhabiting mining environments harbor a diverse array of bacteria with specialized metabolic capacities adapted to extreme conditions. Here, we utilized comparative genome-resolved metagenomics of a high-quality Illumina-sequenced sample from the Cauquenes copper tailing in central Chile. We investigate the metabolic roles and evolutionary behaviors of the resident microorganisms, focusing on capacities related to copper, iron, and sulfur metabolism. We recovered 44 medium and high-quality metagenome-assembled genomes (MAGs), primarily classified belonging to phylum Actinobacteriota (21), Proteobacteria (10), and Acidobacteriota (6). These MAGs were compared to the Global Soil MAGs project (SMAG catalog), which includes bacteria from conventional or natural ecosystems, to uncover specialized properties of mining bacteria. Notably, we discovered a new phylum, Nitrospirota_A, and provided insights into the unexplored taxonomic classifications at the lowest ranks such as genus and species. Functional potential analysis revealed that the mining community has enhanced molecular capabilities associated with sulfur and copper metabolism. Evolutionary analysis revealed that mining genes involved in targeted metabolism are under strong negative selection, indicating conservative evolutionary pressure within the mining environment. In particular, it was possible to identify a MAG from the genus Acidithrix with a global dN/dS ratio greater than 1, suggesting positive selection. Additionally, core proteins essential for bacterial survival, such as flagellar motors, cell cycle regulators, and biogenesis proteins, were also under positive selection. The latter points to the need for enhanced mobility in these microorganisms to locate resources efficiently. We demonstrate that copper mining communities are diverse and possess a significant metabolic repertoire under extreme conditions in sulfur and copper proteins. Those specialized genes appear to be in a conservative state rather than undergoing adaptive evolution. This study enhances our understanding of extremophile mining microbiomes, highlighting their high variability in classification, metabolic functions, evolution, and adaptation, which can be leveraged for further biotechnological applications.

genomics↗

bioRxiv2022

A molecular phenotypic map of Malignant Pleural Mesothelioma

BackgroundMalignant Pleural Mesothelioma (MPM) is a rare understudied cancer associated with exposure to asbestos. So far, MPM patients have benefited marginally from the genomics medicine revolution due to the limited size or breadth of existing molecular studies. In the context of the MESOMICS project, we have performed the most comprehensive molecular characterization of MPM to date, with the underlying dataset made of the largest whole genome sequencing series yet reported, together with transcriptome sequencing and methylation arrays for 120 MPM patients. ResultsWe first provide comprehensive quality controls for all samples, of both raw and processed data. Due to the difficulty in collecting specimens from such rare tumors, a part of the cohort does not include matched normal material. We provide a detailed analysis of data processing of these tumor-only samples, showing that all somatic alteration calls match very stringent criteria of precision and recall. Finally, integrating our data with previously published multi-omic MPM datasets (n=374 in total), we provide an extensive molecular phenotype map of MPM based on the multi-task theory. The generated map can be interactively explored and interrogated on the UCSC TumorMap portal (https://tumormap.ucsc.edu/?bookmark=746c4bc0e8bc4eb5f280cdd8lc7dcc783955faf2e2b493d0d205b7dle92b98c4). ConclusionsThis new high quality MPM multi-omics dataset, together with the state-of-art bioinformatics and interactive visualization tools we provide, will support the development of precision medicine in MPM that is particularly challenging to implement in rare cancers due to limited molecular studies.

genomics↗

bioRxiv2021

Disentangling heterogeneity of Malignant Pleural Mesothelioma through deep integrative omics analyses

Malignant Pleural Mesothelioma (MPM) is an aggressive cancer with rising incidence and challenging clinical management. Using the largest series of whole-genome sequencing data integrated with transcriptomic and epigenomic data using multi-omic factor analysis, we demonstrate that MPM heterogeneity arises from four sources of variation: tumor cell morphology, ploidy, adaptive immune response, and CpG island methylator phenotype. Previous genomic studies focused on describing only the tumor cell morphology factor, although we robustly find the three other sources in all publicly available cohorts. We prove how these sources of variation explain the biological functions performed by the cancer cells, and how genomic events shape MPM molecular profiles. We show how these new sources of variation help understand the heterogeneity of the clinical behavior of MPM and drug responses measured in cell lines. These findings unearth the interplay between MPM functional biology and its genomic history, and ultimately, inform classification, prognostication and treatment. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/461908v1_ufig1.gif" ALT="Figure 1"> View larger version (44K): org.highwire.dtl.DTLVardef@b6c43corg.highwire.dtl.DTLVardef@10d45a9org.highwire.dtl.DTLVardef@58746eorg.highwire.dtl.DTLVardef@143f880_HPS_FORMAT_FIGEXP M_FIG C_FIG

cancer biology↗

bioRxiv2021

The genome sequence of the cereal pest Sitophilus oryzae: an unprecedented transposable element content

BackgroundThe rice weevil Sitophilus oryzae is one of the most important agricultural pests, causing extensive damage to cereal in fields and to stored grains. S. oryzae has an intracellular symbiotic relationship (endosymbiosis) with the Gram-negative bacterium Sodalis pierantonius and is a valuable model to decipher host-symbiont molecular interactions. ResultsWe sequenced the Sitophilus oryzae genome using a combination of short and long reads to produce the best assembly for a Curculionidae species to date. We show that S. oryzae has undergone successive bursts of transposable element (TE) amplification, representing 72% of the genome. In addition, we show that many TE families are transcriptionally active, and changes in their expression are associated with insect endosymbiotic state. S. oryzae has undergone a high gene expansion rate, when compared to other beetles. Reconstruction of host-symbiont metabolic networks revealed that, despite its recent association with cereal weevils (30 Kyear), S. pierantonius relies on the host for several amino acids and nucleotides to survive and to produce vitamins and essential amino-acids required for insect development and cuticle biosynthesis. ConclusionsHere we present the genome of an agricultural pest beetle, which may act as a foundation for pest control. In addition, S. oryzae may be a useful model for endosymbiosis, and studying TE evolution and regulation, along with the impact of TEs on eukaryotic genomes.

genomics↗

bioRxiv2019

Wengan: Efficient and high quality hybrid de novo assembly of human genomes

The continuous improvement of long-read sequencing technologies along with the development of ad-doc algorithms has launched a new de novo assembly era that promises high-quality genomes. However, it has proven difficult to use only long reads to generate accurate genome assemblies of large, repeat-rich human genomes. To date, most of the human genomes assembled from long error-prone reads add accurate short reads to further polish the consensus quality. Here, we report the development of a novel algorithm for hybrid assembly, WO_SCPCAPENGANC_SCPCAP, and the de novo assembly of four human genomes using a combination of sequencing data generated on ONT PromethION, PacBio Sequel, Illumina and MGI technology. WO_SCPCAPENGANC_SCPCAP implements efficient algorithms that exploit the sequence information of short and long reads to tackle assembly contiguity as well as consensus quality. The resulting genome assemblies have high contiguity (contig NG50:16.67-62.06 Mb), few assembly errors (contig NGA50:10.9-45.91 Mb), good consensus quality (QV:27.79-33.61), and high gene completeness (BO_SCPCAPUSCOC_SCPCAP complete: 94.6-95.1%), while consuming low computational resources (CPU hours:153-1027). In particular, the WO_SCPCAPENGANC_SCPCAP assembly of the haploid CHM13 sample achieved a contig NG50 of 62.06 Mb (NGA50:45.91 Mb), which surpasses the contiguity of the current human reference genome (GRCh38 contig NG50:57.88 Mb). Providing highest quality at low computational cost, WO_SCPCAPENGANC_SCPCAP is an important step towards the democratization of the de novo assembly of human genomes. The WO_SCPCAPENGANC_SCPCAP assembler is available at https://github.com/adigenova/wengan

bioinformatics↗

bioRxiv2018

Whole genome sequence of Mapuche-Huilliche Native Americans

BackgroundWhole human genome sequencing initiatives provide a compendium of genetic variants that help us understand population history and the basis of genetic diseases. Current data mostly focuses on Old World populations and information on the genomic structure of Native Americans, especially those from the Southern Cone is scant.\n\nResultsHere we present a high-quality complete genome sequence of 11 Mapuche-Huilliche individuals (HUI) from Southern Chile (85% genomic and 98% exonic coverage at > 30X), with 96-97% high confidence calls. We found approximately 3.1x106 single nucleotide variants (SNVs) per individual and identified 403,383 (6.9%) of novel SNVs that are not included in current sequencing databases. Analyses of large-scale genomic events detected 680 copy number variants (CNVs) and 4,514 structural variants (SVs), including 398 and 1,910 novel events, respectively. Global ancestry composition of HUI genomes revealed that the cohort represents a marginally admixed population from the Southern Cone, whose genetic component is derived from early Native American ancestors. In addition, we found that HUI genomes display highly divergent and novel variants with potential functional impact that converge in ontological categories essential in cell metabolic processes.\n\nConclusionsMapuche-Huilliche genomes contain a unique set of small- and large-scale genomic variants in functionally linked genes, which may contribute to susceptibility for the development of common complex diseases or traits in admixed Latinos and Native American populations. Our data represents an ancestral reference panel for population-based studies in Native and admixed Latin American populations.

genomics↗

bioRxiv2017

FAST-SG: An alignment-free algorithm for hybrid assembly

Long read sequencing technologies are the ultimate solution for genome repeats, allowing near reference level reconstructions of large genomes. However, long read de novo assembly pipelines are computationally intense and require a considerable amount of coverage, thereby hindering their broad application to the assembly of large genomes. Alternatively, hybrid assembly methods which combine short and long read sequencing technologies can reduce the time and cost required to produce de novo assemblies of large genomes. In this paper, we propose a new method, called FAST-SG, which uses a new ultra-fast alignment-free algorithm specifically designed for constructing a scaffolding graph using light-weight data structures. FAST-SG can construct the graph from either short or long reads. This allows the reuse of efficient algorithms designed for short read data and permits the definition of novel modular hybrid assembly pipelines. Using comprehensive standard datasets and benchmarks, we show how FAST-SG outperforms the state-of-the-art short read aligners when building the scaffolding graph, and can be used to extract linking information from either raw or error-corrected long reads. We also show how a hybrid assembly approach using FAST-SG with shallow long read coverage (5X) and moderate computational resources can produce long-range and accurate reconstructions of the genomes of Arabidopsis thaliana (Ler-0) and human (NA12878).

bioinformatics↗

bioRxiv2017

The genome sequence of the soft-rot fungus Penicillium purpurogenum reveals a high gene dosage for lignocellulolytic enzymes

The high lignocellulolytic activity displayed by the soft-rot fungus P. purpurogenum has made it a target for the study of novel lignocellulolytic enzymes. We have obtained a reference genome of 36.2Mb of non-redundant sequence (11,057 protein-coding genes). The 49 largest scaffolds cover 90% of the assembly, and CEGMA analysis reveals that our assembly covers most if not all all protein-coding genes. RNASeq was performed and 93.1% of the reads aligned within the assembled genome. These data, plus the independent sequencing of a set of genes of lignocellulose-degrading enzymes, validate the quality of the genome sequence. P. purpurogenum shows a higher number of proteins with CAZy motifs, transcription factors and transporters as compared to other sequenced Penicillia. These results demonstrate the great potential for lignocellulolytic activity of this fungus and the possible use of its enzymes in related industrial applications.

genomics↗