Biology subjects

Rodrigues, M.

Publications and source records attributed to Rodrigues, M..

At least 19 recordsLinked to original sources

bioRxiv2026

Type 6 secretion systems of adherent-invasive Escherichia coli isolated from Crohn's disease patients shape intestinal microbiota.

Adherent Invasive Escherichia coli (AIEC) colonize the ileal mucosa of Crohn's disease patients. Among bacterial virulence factors potentially implicated, type 6 secretion systems (T6SS) are molecular machineries sending effectors in prokaryotic or eukaryotic target cells. Two T6SS have been reported in AIEC LF82 reference strain. Here, we show that T6SS genes are more prevalent in Crohn's disease patients' microbiota compared to healthy controls, and that T6SS are more frequent in AIEC pathovar compared to E. coli in general and associated with FimH pathoadaptive polymorphism. The use of an in vitro gastrointestinal system coupled with T6SS promoter reporter assay highlighted expression of LF82 T6SS under gastrointestinal conditions, with a major role for bile salts. In mice infected with AIEC LF82 versus T6SS-deleted mutants, T6SS showed a functional impact in modulating the composition of mucosa-associated gut microbiota. Thus, AIEC may use their T6SS to compete with endogenous microbiota to colonize host mucosa.

microbiology↗

bioRxiv2026

Improved detection and spatiotemporal spectral analysis of neural traveling waves

Traveling waves (TWs) are a fundamental mode of neural dynamics, yet existing detection methods are limited by sensor geometry, spatial-frequency resolution, signal amplitude, and ambiguity between propagating and standing-wave patterns. Here we introduce the Traveling Wave Index (TWINDEX), a framework for three-dimensional spatiotemporal spectral analysis of TWs across temporal frequency, spatial frequency, and propagation direction. TWINDEX generalizes to irregular sensor layouts, and quantifies wave strength as the reduction in circular phase variance produced by a candidate planar wave. This normalization yields robust behavior at both low and high spatial frequencies and suppresses coherent in-phase activity. Directional moments further separate planar from standing waves. We derive analytical links between TWINDEX, parametric planar-wave fit, and distance-phase correlation, and introduce projected distance-phase correlation (ProDPC) for sensitive single-trial planar-wave detection. Applying these methods to large-scale marmoset ECoG and human EEG, we identify alpha/low-beta TWs localized in spatial and temporal frequency, with physiologically plausible propagation speeds. Across trials and epochs, waves occur in oppositely directed propagation modes, demonstrating that alpha/beta activity is associated with both feedforward- and feedback-directed large-scale dynamics.

neuroscience↗

bioRxiv2026

Quantification of X-chromosome inactivation in fibroblast and iPSC models of UBQLN2 ALS/FTD using allele-selective qPCR

Pathogenic missense variants in the X chromosome gene UBQLN2 cause amyotrophic lateral sclerosis (ALS), often accompanied by frontotemporal dementia (FTD). As an X-linked gene, UBQLN2 is subject to X chromosome inactivation (XCI), a process wherein one X chromosome in each cell is randomly inactivated to a Barr body throughout the body in females, creating a mosaic of allelic expression in the tissues of heterozygotes. Despite heterozygous females constituting a majority of reported cases of UBQLN2-linked ALS/FTD, and the known influence of XCI on neurological disorders at large, no current disease models account for XCI. Here we report the characterisation of 12 iPSC clones carrying the ALS/FTD-causing p.T487I (c.1460C>T) UBQLN2 variant. These clones, originally derived from 3 heterozygous carrier fibroblast lines, underwent validation of homeostatic Barr body retention. Erosion of XCI in a subset of the lines was correlated with biallelic expression (of both wildtype and mutant UBQLN2), as measured through a novel allele-selective qPCR (AS-qPCR) assay and verified by amplicon-based Illumina sequencing and Sanger chromatogram quantification, enabling selection of iPSC clones best retaining XCI. Together, this UBQLN2 AS-qPCR assay and selected iPSC clones will enable studies of the role of XCI and its skew in female resilience to UBQLN2 p.T487I-linked ALS/FTD and enable development of allele-selective therapies.

molecular biology↗

bioRxiv2026

Genomic variation and ancestry of Helicobacter pylori in the admixed population of Cabo Verde reveal host adaptation, limited host-pathogen ancestry concordance, and signatures of trans-Atlantic slave trade migrations

The genomic structure of the stomach-colonising, gastric cancer-associated bacterium Helicobacter pylori mirrors human evolutionary history, making it difficult to disentangle shared ancestry from true host-pathogen interactions driving disease risk. Recently admixed populations offer opportunities for new coevolutionary trajectories between H. pylori and its host that may disrupt parallel evolution. Here, we analyse host H. pylori IgG, blood serum biomarkers, and paired host-bacterial genomic data from the general population (independent of dyspepsia symptoms) of Cabo Verde. Seropositivity is high (82.8%), as in neighbouring African populations. Serum biomarkers indicate that this unique cohort mainly comprises hosts with limited gastric inflammation. Genomic analyses show that Cabo Verdean H. pylori derive European (hspSWeurope) and West African (hspAfrica1WAfrica) ancestry. The delineation of a reference dataset that includes new strains from Ghana and Portugal, uncovered a distinct West-Central African cluster (hspAfrica1WCAfrica). This dataset allowed inference of within-Africa and within-Europe ancestries in Cabo Verdean and American strains that reflect historical migrations linked to European colonisation and the trans-Atlantic Slave Trade. European strains in Cabo Verde show additional population structure, including two low-diversity clusters. Approximate Bayesian Computation (ABC) inference indicates that the most common cluster represents a clonal expansion, likely driven by host adaptation leading to increased transmission within Cabo Verde. Notably, these strains lack known virulence genes and show significant divergence from gastric cancer strains. Finally, host and bacterial ancestry are uncoupled, indicating disruption of ancestral parallel evolution. Cabo Verde, therefore, provides a unique natural model for studying host-pathogen interactions underlying susceptibility to H. pylori.

evolutionary biology↗

bioRxiv2026

Reversion mutations define minimal BRCA1/2 requirements for therapy resistance

Although platinum salts or PARP inhibitors are effective in delivering anti-tumor responses in people with BRCA1 or BRCA2 mutated cancers, drug resistance is common and is often caused by secondary BRCA1/2 reversion mutations that restore function. By collating and analyzing 848 BRCA1/2 reversion mutations in 384 cancer patients with drug resistance, we confirm that pathogenic BRCA1/2 mutation type influences the acquisition of reversions, and that large BRCA1/2 deletions are an underappreciated form of reversion. Integrating reversion data with systematic CRISPR-Cas9 screens that delete BRCA1/2 exons, we also show that both proteins contain privileged domains whose structure is essential for drug resistance, including the PALB2 interacting domains of both BRCA1 and BRCA2. Reversions in PALB2 also conserve both BRCA1 and BRCA2 binding domains. Surprisingly, exon 11 of BRCA2, which encodes BRC repeats 1-8, is not essential for resistance. Using this patient and functional information, we estimate the likelihood of pathogenic BRCA2 mutations to revert. We show that risk of reversion correlates with both the presence of clinical reversions and the response to treatment, suggesting that the propensity to revert could be a useful clinical parameter.

cancer biology↗

bioRxiv2026

Human PMS1-dependent non-canonical mismatch repair converges with MBD4 to repair 5-methylcytosine deamination

CpG dinucleotides are hotspots for mutagenesis by spontaneous deamination of 5-methylcytosine (5mC) into thymine, resulting in T:G mismatches that can lead to C>T transitions. These mutations are a hallmark of aging and cancer and a major force shaping the evolution of vertebrate genomes. We have previously uncovered MBD4 as the primary base excision repair (BER) glycosylase responsible for 5mC deamination repair. In this study, we employ a cytosine base-editing system, comprising an APOBEC1 deaminase fused to a catalytically dead Cas9, to induce targeted cytosine deamination in native chromatin and track its repair. This approach reveals that MBD4 cooperates with a non-canonical branch of mismatch repair (MMR) to elicit 5mC deamination repair. We demonstrate that MBD4 activity depends on MMR complexes MutS (MSH2-MSH6) and MutL{beta} (MLH1-PMS1), but not on post-replicative MMR elicited by the MutL (MLH1-PMS2) complex. We find that PMS1 loss phenocopies the genome-wide CpG>TpG hypermutated profile associated with MBD4 deficiency, uncovering that 5mC deamination repair may represent one of the primary functions of the MutL{beta} complex. The mutational landscape of MMR-deficient tumors aligns with our experimental results, showing that replication-independent CpG>TpG mutagenesis partly contributes to the mutational burden of tumors inactivated for MLH1, MSH2 and MSH6. Finally, using structural predictions alongside biochemical validation, we show that MBD4 physically interacts with MutL{beta} in an MLH1-dependent manner, illuminating the structural basis for the convergence of the BER and MMR pathways. Altogether, we uncover a novel function of non-canonical MMR that underscores its interplay with BER in safeguarding genomic integrity against damage to methylated DNA.

molecular biology↗

bioRxiv2025

Exploiting pair correlation function to describe biological tissue structure

Multiplexed imaging technologies now enable the simultaneous profiling of hundreds to thousands of molecular targets in intact tissues, providing unprecedented insight into cellular heterogeneity and spatial organization. While data generation has rapidly matured, the quantitative analysis of spatial structure remains challenging and poorly standardized, particularly across biological length scales. Existing approaches, such as distance-based metrics, neighborhood analyses and graph neural networks, either capture only local interactions or sacrifice interpretability for predictive power. Here we introduce PCF-SiM (Pair Correlation Function Sigmoid Modeling), a scalable and interpretable framework that leverages parametric modeling of the pair correlation function to quantify spatial organization in multiplexed imaging data. PCF-SiM compresses complex spatial patterns into a small set of biologically meaningful parameters, enabling robust comparisons across cell types, samples and conditions. Applying PCF-SiM to diverse public spatial transcriptomics datasets, we demonstrate its ability to detect condition-dependent tissue remodeling in a mouse colitis model. We further extend the framework with a co-scaling strategy that identifies cell types participating in shared spatial structures. Using newly generated clinical datasets from Hashimotos thyroiditis and uveal melanoma liver metastases, PCF-SiM reveals hierarchical organization of autoimmune infiltrates and coordinated spatial interactions between lymphatic endothelial cells and tumor-infiltrating lymphocytes. Finally, we show that reliable inference of tissue-scale architecture requires whole-slide imaging, exposing intrinsic limitations of tumor microarray-based spatial analyses. Together, PCF-SiM provides a principled and interpretable approach for spatial analysis of multiplexed imaging data.

bioinformatics↗

bioRxiv2025

Ancient balanced polymorphism underlies long-standing adaptation for seasonal camouflage in the least weasel

Unraveling how adaptive traits originate and evolve is key to understanding the mechanisms shaping species diversity and their adaptive potential. Seasonal color molts, from summer-brown to winter-white, evolved in at least 21 mammals and birds to maintain camouflage in environments with seasonal snow, but the occurrence of winter-brown morphs reflects seemingly convergent local adaptation to distinct snow conditions. In the least weasel (Mustela nivalis), alternative winter morphs map to the pigmentation gene MC1R, but the evolutionary history and functional basis of this variation remain unknown. Using in vitro cellular assays, we show that winter-brown coats are caused by a derived protein-coding amino acid substitution that reduces MC1R affinity to its ligands, ASIP and -MSH. Using targeted enrichment and sequencing, we find that this mutation arose de novo within the species, around one million years ago, and was maintained across the geographically structured populations generated during its evolution in Europe. Using simulations, we show that genetic drift cannot explain the long-term maintenance of this variant, which is likely driven by spatially varying selection acting on the phenotypic polymorphism, anchoring local adaptive responses. Our results underscore how long-standing adaptive variation can fuel recurrent adaptation to heterogeneous environments through time.

evolutionary biology↗

bioRxiv2025

Long-Read Sequencing of the MUC1 VNTR: Genomic Variation, Mutational Landscape, and Its Impact on ADTKD Diagnosis and Progression

BackgroundADTKD-MUC1 is caused by frameshift mutations in MUC1 gene that produce a frameshifted protein (MUC1fs) toxic to kidney cells. The genes variable number of tandem repeats (VNTR), with high GC content, makes it largely inaccessible to standard sequencing. As a result, both the reference sequence and natural variation in this region remain poorly defined, complicating mutation detection and data interpretation. Standard methods also fail to pinpoint the exact VNTR unit affected, limiting insight into mutation mechanisms and genotype-phenotype correlations. MethodsWe employed Single Molecule, Real-Time (SMRT) sequencing and characterized the genomic sequence of MUC1 in 300 individuals including 279 individuals from 143 families suspected of having ADTKD-MUC1. We compared these results to those obtained using the CLIA-approved mass spectrometry-based probe extension (PE) assay, which specifically detect the most prevalent 59dupC mutation. We correlated the structural features of the MUC1 VNTR with the rate of kidney function decline in affected individuals. ResultsWe identified MUC1 consensus sequences for 205 unique VNTR alleles, with 9 distinct types of frameshift mutations present on 52 distinct mutated VNTR alleles. MUC1 frameshift mutations were identified in 71 of 143 families (50%) with suspected ADTKD, comprising 135 genetically affected individuals (48%). The SMRT assay exhibited complete concordance and revealed that the PE assay is capable of detecting frameshift mutations in approximately 85% of affected families. The constellation of VNTR structures supports a genotype-progression model, in which fast progressors exhibit a significantly lower number of repeat units on the wild-type allele and a higher number of repeats on the mutation-bearing allele, including an increased number of frameshifted repeat units. ConclusionsSMRT sequencing outperforms current diagnostic methods for ADTKD-MUC1 and reveals the prognostic value of VNTR structures. Although their contribution to disease progression is modest ([~]6% variance explained), it remains biologically and clinically meaningful. Key Points 3O_LISingle Molecule, Real-Time (SMRT) sequencing of MUC1 outperforms existing genetic and immunohistochemical methods for ADTKD-MUC1 diagnosis. C_LIO_LICLIA-approved mass spectrometry-based genotyping assay, complemented by SMRT sequencing, can detect nearly all ADTKD-MUC1 patients. C_LIO_LIDisease progression correlates with VNTR pattern: fast progressors have fewer WT repeats and more mutant/frameshifted repeats C_LI

genetics↗

bioRxiv2025

Impact of storage on the stability and the protective effect of extracellular vesicles released by Candida albicans

Extracellular vesicles (EVs) released by Candida albicans are multi-antigenic compartments considered as promising prototypes for vaccine development. However, their stability, appropriate storage and handling conditions are largely unexplored, which raises questions related to their biotechnological applicability. Here, we evaluated the physical and functional stability of C. albicans EVs under long-term storage. Furthermore, we conducted a comparative analysis of these properties in C. albicans EVs obtained through three commonly utilized isolation protocols documented in the literature. After identifying the most efficient isolation method for optimal yield, we devised a potential quality control for EVs isolation based on protein and sterol ratio. Subsequently, we investigated the impact of drying EVs using vacuum centrifugation at room temperature or -4 {degrees}C and the effect of freeze-thaw cycles in EVs stability. Transmission electron microscopy (TEM) revealed that EVs maintained morphological stability after long-term (up to 4 years) storage at -80 {degrees}C as well as storage at room temperature, 4 {degrees}C and -20 {degrees}C for 7 days with or without vacuum centrifugation, with a tendency of higher recovery when lower temperature is used. Remarkably, all of the C. albicans EVs suspensions maintained their biological properties as demonstrated by their ability to protect Galleria mellonella against C. albicans infection. However, the number of freeze-thaw cycles significantly impacted on the protective effect of the EVs. Overall, our findings demonstrate that C. albicans EVs maintain notable morphological and biological stability of under several conditions, enabling their efficient and reproducible utilization in research and potentially as therapeutic agents. ImportanceExtracellular vesicles (EVs) released by Candida albicans are promising vaccine prototypes due to their multi-antigenic nature. However, their storage and handling conditions are not well understood, raising concerns about their biotechnological use. This study evaluated the long-term physical and functional stability of C. albicans EVs. We compared three isolation methods to identify the most effective one and suggested a quality control measure based on protein and sterol ratios. We also examined the effects of vacuum drying and freeze-thaw cycles on EV stability. Our findings show that C. albicans EVs maintain their biological function after long-term storage at -80 {degrees}C and under various conditions. Notably, their protective effect in an insect model was reduced though repeated freeze-thaw cycles. This research provides valuable insights for the efficient use of these vesicles in future studies.

microbiology↗

bioRxiv2025

Voltage-dependent reversal potentials in spiking recurrent neural networks enhance energy efficiency and task performance

Spiking recurrent neural networks (SRNNs) rival gated RNNs on various tasks, yet they still lack several hallmarks of biological neural networks. We introduce a biologically grounded SRNN that implements Dales law with voltage-dependent AMPA and GABA reversal potentials. These reversal potentials modulate synaptic gain as a function of the postsynaptic membrane potential, and we derive theoretically how they make each neurons effective dynamics and subthreshold resonance input-dependent. We trained SRNNs on the Spiking Heidelberg Digits dataset, and show that SRNN with reversal potentials cuts spike energy by up to 4x, while increasing task accuracy. This leads to high-performing Dalean SRNNs, substantially improving on Dalean networks without reversal potentials. Thus, Dales law with reversal potentials, a core feature of biological neural networks, can render SRNNs more accurate and energy-efficient.

neuroscience↗

bioRxiv2025

Mitochondrial DNA variation of the striped hyena (Hyaena hyaena) in Algeria and further insights into the species' evolutionary history

The striped hyena (Hyaena hyaena) occurs in a wide range from north and east Africa, through southwest Asia to India, but its distribution is increasingly patchy and many of its populations are in decline due to intense human pressure. Its genetic diversity and structure, phylogeography, and evolutionary history, remain poorly understood. In this study, we investigated mitochondrial DNA variation in Algerian striped hyenas. Moreover, with the aim of contributing to our understanding of the evolutionary history of the species, we also examined samples from other geographic regions and compared our results with those of the only previous study in which individuals from across the range of the species were analysed. In particular, we performed a wide range of analyses of demographic history and estimation of the age of the extant mitochondrial DNA variation. The Algerian population sample was monomorphic. Overall, the global patterns of genetic diversity and the results of some demographic history analyses supported a scenario of population growth in the species, estimated to have occurred in the Late Pleistocene, but many of the analyses did not detect a significant signal of growth, most likely a result of the limited power provided by a small number of segregating sites. The estimates, from three different methods, for the time to the most recent common ancestor (TMRCA) of the mitochondrial DNA variation hovered around 400 ka, coinciding with one of the longest and warmest interglacials of the last 800,000 years, with environmental conditions similar to the Holocene.

evolutionary biology↗

bioRxiv2025

Cross-Species Communication via Fungal Extracellular Vesicles

Extracellular vesicles (EVs) play crucial roles in fungal communication and host immune modulation, representing potential therapeutic targets for fungal infections. This study investigated the role of fungal EVs in both intra- and interspecies communication, focusing on their effects on virulence and immune responses. Co-incubation experiments were performed using EVs derived from Candida albicans and Candida auris to assess interactions with C. albicans planktonic cells and biofilms, as well as Cryptococcus neoformans and Cryptococcus gattii EVs interacting with C. neoformans cultures. EVs were observed associating with recipient cell surfaces, suggesting subsequent internalization. Functional assays revealed that EV exposure led to increased expression of Cap59, Lac1, Ure1, and Erg11 genes, correlating with reduced antifungal susceptibility in both planktonic and biofilm forms. Additionally, EVs facilitated cross-species communication, enhancing biofilm adhesion and dispersion, which underscores their role in phenotypic modulation. Macrophages stimulated with fungal EVs exhibited receptor-specific gene expression changes, notably the upregulation of galectin-3, along with a pro-inflammatory phenotype marked by increased iNOS expression and elevated cytokine levels (IL-1{beta}, IL-6, and IL-8). Collectively, these findings underscore a critical role for fungal EVs in interspecies communication, biofilm regulation, and immune modulation, offering valuable insights into fungal pathogenicity mechanisms. ImportanceCurrently, no vaccines exist to prevent fungal infections, underscoring the need for new therapies. As fungal diseases increase globally, understanding fungal biology is essential to identifying treatment targets. Fungi use EVs to communicate and evade immune responses. EVs mediate cell-cell communication, transporting proteins, polysaccharides, lipids, and nucleic acids - serving as "messages" exchanged within a fungal network. Understanding how these vesicles facilitate communication not only within a single species but also across different fungal species can shed light on their contribution to infection persistence and cross-species adaptability. Moreover, EVs may have a broader role in inter-kingdom communication, influencing how fungi interact with host immune cells. The impact of fungal EVs on human innate immune responses remains a largely underexplored area, with significant gaps in our knowledge. This study aims to examine how fungal EVs affect immune responses and whether their signaling varies across species, potentially revealing new therapeutic targets.

microbiology↗

bioRxiv2024

Usutu virus African 3.1 lineage, Portugal, 2021-2023

BackgroundUsutu virus (Orthoflavivirus usutuense, USUV), a neurotropic arthropod-borne RNA virus of the family Flaviviridae, is a zoonotic virus that has spread throughout the European continent over the last three decades, since its emergence in Italy in 1996. However, no cases of USUV have been reported in Portugal so far. Material and methodsIn the scope of an active surveillance program for Orthoflavivirus, we collected growing feather samples from 249 red-legged partridges (Alectoris rufa) hunted in southern Portugal during the 2021-2023 hunting seasons. Samples positive for USUV were subjected to whole genome sequencing and strain characterization. ResultsTwo partridges tested positive for USUV. Phylogenetic analyses of whole and partial genomes assigned the USUV strains to the African 3 lineage, specifically the African 3.1 sub-lineage. ConclusionsOur study confirms, for the first time, the circulation of USUV in wild birds in Portugal. Active surveillance of hunted partridges proved to be a useful, accessible, and cost-effective method for USUV monitoring, further supporting their value as effective sentinels for Orthoflavivirus surveillance. Given the ongoing circulation of USUV and the increasing risk of its spillover to other domestic and wild animals, and humans, additional efforts are needed to improve virus surveillance in Portugal from a One Health perspective.

microbiology↗

bioRxiv2024

Stress in utero: effects on gliovascular integrity in female infant offspring

From early in life, experiences like prenatal stress profoundly affect long-term health and behavior. Maternal stress increases fetal exposure to glucocorticoids (GC), disrupting neurodevelopment and raising susceptibility to psychiatric disorders. Previous studies on synthetic GCs, such as dexamethasone (DEX), revealed impairments in neurogenesis and dendritic spine development. However, the influence of prenatal stress on the gliovascular interface remains unclear. This interface, involving the relationship between astrocytes and blood vessels, is essential for healthy brain development. Our study demonstrates that prenatal stress alters the expression and localization of astrocytic proteins crucial for maintaining vascular homeostasis, such as aquaporin-4, in female offspring exposed to DEX. While overall vascular density remains unaffected, it triggers morphological changes. Particularly, the hippocampus and prefrontal cortex exhibit heightened vulnerability to these effects. This study reveals prenatal stress as a potent disruptor of gliovascular development, urging deeper inquiry into its implications.

neuroscience↗

bioRxiv2024

Alpha-synuclein aggregates trigger anti-viral immune pathways and RNA editing in human astrocytes

RNA editing is a post transcriptional mechanism that targets changes in RNA transcripts to modulate innate immune responses. We report the role of astrocyte specific, ADAR1 mediated RNA editing in neuroinflammation in Parkinsons disease. We generated hiPSC-derived astrocytes, neurons and co-cultures and exposed them to small soluble alpha-synuclein aggregates. Oligomeric alpha-synuclein triggered an inflammatory glial state associated with TLR activation, viral responses, and cytokine secretion. This reactive state resulted in loss of neurosupportive functions, and the induction of neuronal toxicity. Notably, interferon response pathways were activated leading to upregulation, and isoform switching of the RNA deaminase enzyme, ADAR1. ADAR1 mediates A-to-I RNA editing, and increases in RNA editing were observed in inflammatory pathways in cells, as well as in post-mortem human PD brain. Aberrant, or dysregulated, ADAR1 responses and RNA editing may lead to sustained inflammatory reactive states in astrocytes triggered by alpha-synuclein aggregation, and this may drive the neuroinflammatory cascade in Parkinsons.

neuroscience↗

bioRxiv2023

Democratizing computational pathology: optimized Whole Slide Image representations for The Cancer Genome Atlas

Automatic analysis of hematoxylin and eosin (H&E) stained Whole Slide Images (WSI) bears great promise for computer assisted diagnosis and biomarker discovery. However, scarcity of annotated datasets leads to underperforming models. Furthermore, the size and complexity of the image data limit their integration into bioinformatic workflows and thus their adoption by the bioinformatics community. Here, we present Giga-SSL, a self-supervised method for learning WSI representations without any annotation. We show that applying a simple linear classifier on the Giga-SSL representations improves classification performance over the fully supervised alternative on five benchmarked tasks and across different datasets. Moreover, we observe a substantial performance increase for small datasets (average gain of 7 AUC point) and a doubling of the number of mutations predictable from WSIs in a pan-cancer setting (from 45 to 93). We make the WSI representations available, compressing the TCGA-FFPE images from 12TB to 23MB and enabling fast analysis on a laptop CPU. We hope this resource will facilitate multimodal data integration in order to analyze WSI in their genomic and transcriptomic context.

bioinformatics↗

bioRxiv2023

CUR(E)ating a New Approach to Study Fungal Effectors and Enhance Undergraduate Education through Authentic Research

Course-based Undergraduate Research Experiences (CUREs) integrate active, discovery-based learning into undergraduate curriculums, adding tremendous value to Biochemistry and Molecular Biology (BMB) education. There are multiple challenges in transforming a research project into a CURE, such as the readiness of students, the time commitment of the instructor, and the productivity of the research. In this article, we report a CURE course developed and offered in the University of Massachusetts Amherst BMB Department since 2018 that addresses these challenges. Our CURE focuses on fungal effectors which are proteins secreted by a destructive pathogenic fungus Fusarium oxysporum, one of the top five most devastating plant pathogens. By studying this group of proteins, students are connected to real-world problems and participate in the search for potential solutions. A three-week "standard Bootcamp" is implemented to help students familiarize themselves with all basic techniques and boost their confidence. Next, molecular cloning, a versatile technique with modularity and repeatability, is used as the bedrock of the course. Our past five years of experience have confirmed that we have developed a novel and feasible CURE protocol. Measurable progress documented by students who took this course includes stimulated active learning and increased career trajectory to pursue hypothesis-based research to address societal needs. In addition, data generated through the course advance ongoing lab research. Collectively, we encourage the implementation of CURE among research-intensive faculty to provide a more inclusive research experience to all students, an important element in predicting career success.

scientific communication and education↗