Biology subjects

Garate, L.

Publications and source records attributed to Garate, L..

8 recordsLinked to original sources

bioRxiv2026

Microbial ecological insights from estuarine sediments revealed by temporal and spatial network analysis

Association network analyses performed on microbial abundance data provides information regarding ecosystems functioning, quality and potential keystone taxa. Samples for network analyses can be collected spatially, temporally or both. Here, we compare the microbiomes and the reconstructed association networks resulting from temporal vs spatial sampling regimes from the Oka estuary in the Spanish Basque Country. The taxonomic composition although similar at Phylum level, diverged more at lower taxonomic levels such as Family. The dissimilarity of spatial replicates was higher than the temporal replicates; however, the dispersion of OTU abundances across samples was similar in the two datasets, indicating that OTU abundances varied similarly across samples. Moreover, the topological properties and keystones differed between networks. The number of edges and the connectance were higher in the spatial network, and keystones were more taxonomically diverse in the temporal network. Among those correlations present in the spatial and temporal networks, we identified potential interactions involved in the sulphur and nitrogen cycles, and in the degradation of organic matter. We conclude that network analyses reveal ecological aspects of the ecosystems functioning, nevertheless, the sampling must be thoroughly planned according to the aim of the study, since different sampling strategies may result in different outcomes.

ecology↗

bioRxiv2026

Mapping Disease Transitions from Premalignant, Asymptomatic to Advanced Myeloma through Integrative Epigenomic and Transcriptional Analyses

AbstractMultiple myeloma (MM) evolves from asymptomatic precursor conditions through progressive genetic and epigenetic remodeling, yet the regulatory mechanisms driving the development toward more active stages of the disease remain poorly understood. Here, we integrated bulk-based paired chromatin accessibility and activation, and transcriptomic profiling across disease stages to map regulatory remodeling during myeloma development. We identified a progressive increase in chromatin accessibility; furthermore, this epigenetic reconfiguration is accompanied by a stage-dependent shift from promoter-centered regulation in precursor states toward enhancer-dominated transcriptional control in active MM. Motif enrichment and regulatory network analyses identified both established and previously underappreciated transcription factors (TFs), including members of the IRF, MEF2, and FOX families, associated with disease-stage-specific transcriptional programs. Among these, MEF2D and FOXK2 emerged as candidate regulators of pathways involved in cell survival and chemotaxis. Functional perturbation demonstrated that MEF2D depletion markedly impaired MM cell viability, whereas inhibition of either MEF2D or FOXK2 reduced chemotactic migration. Together, these findings provide a stage-resolved framework of epigenetic and transcriptional remodeling across myeloma development, revealing regulatory programs established in precursor conditions and progressively reinforced during disease evolution, while identifying candidate transcriptional dependencies with potential biological and therapeutic relevance.

cancer biology↗

bioRxiv2025

Contrasting dynamics and biotic association networks in estuarine microbenthic communities along an environmental disturbance gradient

Estuarine ecosystems experience a range of anthropogenic pressures. Consequently, robust monitoring tools are essential for their management and protection. Utilising environmental DNA in routine monitoring programs enables the inclusion of benthic microorganisms, which are not only good indicators of environmental condition, but also play critical roles in ecosystem functioning. In this study we collect eDNA from sediment samples across time in six estuaries, from the Basque coast (Spain), under varying degrees of disturbance. To identify potential indicators of biotic integrity (environmental health status), we used time series data to examine the prokaryotic microbial communities and consensus networks associated with different levels of pollution. In general, sediment communities were relatively temporally stable, with the moderately and heavily disturbed sites showing more variation. The consensus networks also differed significantly in their topologies, with more impacted estuaries having fewer nodes, edges and connectance, among others, and higher modularity compared to those less impacted. Moreover, the potential keystone taxa and predicted functional profiles differed between consensus networks. This illustrates how modelled association networks can reveal new insights regarding the state of estuarine ecosystems and their potential functional processes.

ecology↗

bioRxiv2022

Ecological assembly of natural soundscapes in the Garajonay National Park (Spain)

Natural sound contains data about the ecology of animal populations, communities, and the full ecosystem, resulting from a complex evolution and varying according to the environment. Amongst the processes that are hypothesized to explain sound assemblages, or soundscapes, one is the acoustic niche hypothesis: sounds produced by species calling at the same time seek avoid overlapping, leading to an acoustic differentiation of signals. Soundscapes are more complex in the most pristine environments and show responses to habitat degradation and physical perturbations; hence here, we focus on La Gomera, in the Canary Islands (Spain). This island is the only location in Europe where primary cloud forests are well preserved and thrive on an island with varied orography, microclimates, disturbances, and vegetation types. In this article, we adapted a method to quantify the importance of acoustic niche partitioning and also the opposite process: acoustic aggregation. To do so, we explored soundscapes at different temporal scales in forests with variable degrees of perturbation and maturity. A secondary goal of this report is to compare how soundscapes could differ in an area affected by a wildfire, and undisturbed equivalents, in summer in winter, seasons with contrasting temperatures and wind regimes. We conclude that tracking faunal activity and behavior through soundscape monitoring could be a piece of useful complementary information to guide conservation decisions and future restoration efforts in the Garajonay National Park (La Gomera). Highlights{circ} The mature forest and the transitional forest are similar in terms of sound levels, frequencies, and dynamics, although the transitional forest had higher sound levels of the lower frequencies (higher NDSI). {circ}The mature forest has stronger and more active assembly mechanisms (i.e., acoustic aggregation and acoustic niche partitioning) and a higher acoustic diversity index (ADI) than the transitional forest. Assembly organizes differently in both locations. {circ}In both the mature and the transitional forests, we found an inverse relationship between the ADI and acoustic niche partitioning. At the highest diversities (more frequency bands occupied), the weakest is the temporal avoidance of calls with similar frequencies. {circ}The vulnerability of the burned location is highest during the harsh summer, but in winter, it hosts a community very similar to the intact vegetation in terms of ADI and sound levels.

ecology↗

bioRxiv2022

gMCStool: automated network-based tool to search for metabolic vulnerabilities in cancer

The development of computational tools for the systematic prediction of metabolic vulnerabilities of cancer cells constitutes a central question in systems biology. Here, we present gMCStool, a freely accessible and online tool that allows us to carry out this task in a simple, efficient and intuitive environment. gMCStool exploits the concept of genetic Minimal Cut Sets (gMCSs), a theoretical approach to synthetic lethality based on genome-scale metabolic networks, including a unique database of thousands of synthetic lethals computed from Human1, the most recent metabolic reconstruction of human cells. Based on RNA-seq data, gMCStool extends and improves our previously developed algorithms to predict, visualize and analyze metabolic essential genes in cancer, demonstrating a superior performance than competing algorithms in both accuracy and computational performance. A detailed illustration of gMCStool is presented for multiple myeloma (MM), an incurable hematological malignancy. gMCStool could identify a synthetic lethal that explains the dependency on CTP Synthase 1 (CTPS1) in a sub-group of MM patients. We provide in vitro experimental evidence that supports this hypothesis, which opens a new research area to treat MM.

systems biology↗

bioRxiv2022

Revealing cell populations catching the early stages of the human embryo development in naive pluripotent stem cells

Naive human pluripotent stem cells (hPSCs) are defined as the in vitro counterpart of the human preimplantation embryos epiblast and are used as a model system to study developmental processes. In this study, we report the discovery and characterization of distinct cell populations coexisting with epiblast-like cells in 5iLAF naive human induced PSCs (hiPSCs) cultures. Noteworthily these populations closely resemble different cell types of the human embryo at early developmental stages. While epiblast-like cells represented the main cell population, interestingly we detected a cell population with gene and transposable element expression profile closely resembling the totipotent 8-Cell (8C) stage human embryo, and three cell populations analogous to trophectoderm (TE) cells at different stages of their maturation process: transition, early and mature stage. Thus, 5iLAF naive hiPSCs cultures provide an excellent opportunity to model the earliest events of human embryogenesis, from the 8C stage to the peri-implantation period. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=105 SRC="FIGDIR/small/482812v2_ufig1.gif" ALT="Figure 1"> View larger version (46K): org.highwire.dtl.DTLVardef@11b680eorg.highwire.dtl.DTLVardef@4c7e0forg.highwire.dtl.DTLVardef@1e84568org.highwire.dtl.DTLVardef@24ee65_HPS_FORMAT_FIGEXP M_FIG C_FIG

cell biology↗

bioRxiv2021

Identifying Lethal Dependencies with HUGE Predictive Power from Large-Scale Functional Genomic Screens

Recent functional genomic screens -such as CRISPR-Cas9 or RNAi screening-have fostered a new wave of targeted treatments based on the concept of synthetic lethality. These approaches identified LEthal Dependencies (LEDs) by estimating the effect of genetic events on cell viability. The multiple-hypothesis problem related to the large number of gene knockouts limits the statistical power of these studies. Here, we show that predictions of LEDs from functional screens can be dramatically improved by incorporating the "HUb effect in Genetic Essentiality" (HUGE) of gene alterations. We analyze three recent genome-wide loss-of-function screens - Project Score, CERES score and DEMETER score-identifying LEDs with 75 times larger statistical power than using state-of-the-art methods. HUGE shows an increased enrichment in a recent harmonized knowledgebase of clinical interpretations of somatic genomic variants in cancer (with an AUROC up to 0.87). Our approach is effective even in tumors with large genetic heterogeneity such as acute myeloid leukemia, where we identified LEDs not recalled by previous pipelines, including FLT3-mutant genotypes sensitive to FLT3 inhibitors. Interestingly, in-vitro validations confirm lethal dependencies of either NRAS or PTPN11 depending on the NRAS mutational status. HUGE will hopefully help discover novel genetic dependencies amenable for precision-targeted therapies in cancer.

genomics↗

bioRxiv2019

Chromatin activation as a unifying principle underlying pathogenic mechanisms in multiple myeloma

Multiple myeloma (MM) is a plasma cell neoplasm associated with a broad variety of genetic lesions. In spite of this genetic heterogeneity, MMs share a characteristic malignant phenotype whose underlying molecular basis remains poorly characterized. In the present study, we examined plasma cells from MM using a multi-epigenomics approach and demonstrated that when compared to normal B cells, malignant plasma cells showed an extensive activation of regulatory elements, in part affecting co-regulated adjacent genes. Among target genes upregulated by this process, we found members of the NOTCH, NFkB, mTOR1 signaling and p53 signaling pathways. Other activated genes included sets involved in osteoblast differentiation and response to oxidative stress, all of which have been shown to be associated with the MM phenotype and clinical behavior. We functionally characterized MM specific active distant enhancers controlling the expression of thioredoxin (TXN), a major regulator of cellular redox status, and in addition identified PRDM5 as a novel essential gene for MM. Collectively our data indicates that aberrant chromatin activation is a unifying feature underlying the malignant plasma cell phenotype.

cancer biology↗