Biology subjects

Vargas, A.

Publications and source records attributed to Vargas, A..

10 recordsLinked to original sources

bioRxiv2026

SVPopEx: Population-Wide Visualization and Exploration of Structural Variants

Structural variants (SVs) are large-scale genomic variants, which can disrupt important functional and regulatory elements, leading to genomic disorders in humans and playing important roles in domestication, disease resistance, and traits in plants. SVs are generated across populations of individuals and used for association studies, consisting of large datasets with thousands of genomic loci. Visualization of these SVs aids in understanding their genomic distribution, identifying patterns across affected or phenotypic groups, and assessing their proximity to other genomic regions of interest. A variety of tools exist for visualizing SVs, including linear genome browsers and graph-based methods; however, many do not offer intuitive or scalable representations of SVs across large populations. To address this, we present SVPopEx, an interactive tool for population-wide visualization and exploration of SVs. SVPopEx provides a unique and intuitive representation for insertions, deletions, inversions, duplications, and translocations in a linear genome-style browser. Novel features were developed to support comparisons across genomes within user-defined regions, including rendering SVs based on one or more samples and visualizing haplotypes. Use of the tool is demonstrated with SV datasets from Schistosoma mansoni and Lens culinaris. A task-based evaluation was conducted using SVPopEx and two other linear genome browsers, which demonstrated that SVPopEx excelled in (1) providing a clear representation of the SVs present and (2) supporting comparisons across genomes.

bioinformatics↗

bioRxiv2024

Variability in mineral composition of Canadian lentil cultivars

Lentils are a good source of essential minerals for the proper functioning of the human body. We evaluated 34 cultivars and elite lentil lines representing the breadth of the Canadian breeding program. Trials were established in 10 site-years across Saskatchewan Province. Concentrations of 27 minerals were quantified with an inductive coupled argon plasma emission spectrometer in whole and dehulled lentil seeds. Li, V, Cr, Co, As, Ag, Cd, Sn, La, Hg, and Pb had concentrations below the quantification limit and were excluded from further analysis. The effects of site year, tissue type (whole and dehulled), and lentil genotypes were analyzed using a mixed model. Mineral concentrations of Na, K, Ca, Mg, Cu, B, and Ba were stable across site years. Na, Zn, P, Cu, Se, and Mo had similar concentrations in whole and dehulled seeds. Ca, Fe, Mg, Mn, B, Al, and Ba were more concentrated in whole seeds, while K, S, and Ni were higher in dehulled seeds. Several lentil genotypes had outstanding concentrations of several minerals. Lentil genotypes with a higher composition of several minerals could be a starting point for enhancing mineral composition in lentils.

genetics↗

bioRxiv2024

Detecting color differences in lentil flour samples using an inexpensive, hand-held colorimeter.

Our lentil breeding program was interested in determining the effects of the red lentil genotype in processed food products colour intensity. This required a colorimeter that could accurately assess colour from the CIE L*a*b* colour space on a small sample of milled flour. Flour colour is commonly assessed with industry standard HunterLab colorimeters that require a large sample size ([~]6g flour/sample). In recent years a new spectrophotometer (Nix) has become available. It was designed to quickly and accurately obtain CIEL*a*b* values for everyday items and requires a small amount of sample for analysis (0.5 g flour/sample), but its use has not been tested in milled flour products. To test whether this instrument was appropriate for milled flour colour, eight red lentil genotypes were evaluated for red colour using both instruments. Mean colour scores with Nix (a* and b*) were comparable to those obtained with the HunterLab (r2 = 0.9-0.95), L* scores were less comparable (r2 = 0.58-0.61). Both instruments were able to differentiate and rank red colour intensity in milled flour from the different red lentil genotypes. Nix procedures are more repeatable and use less sample than HunterLab validating its use for assessing red colour intensity in lentil flour. Research HighlightsO_LICompanies making foods using red lentil flour seek red lentil genotypes that exhibit red colour intensity. C_LIO_LINix Spectro2 is an inexpensive photospectrometer made for small volume samples. It has not been tested on flour products. C_LIO_LIThe selected red lentil genotypes tested showed a range of red colour intensities. C_LIO_LINix Spectro2 performance was comparable to industry standard HunterLab colorimeter. C_LI

systems biology↗

bioRxiv2023

Heterospecific developmental models highlight therole of FBXO32 in neural crest lineages and thesignificance of its variant in pediatric melanoma

Melanoma is a rare sporadic pediatric cancer caused by de novo genetic accidents. To analyze the involvement of FBXO32 of unknown biological significance, we set up original developmental in vivo, ex vivo, and in vitro models to unmask the biological role of FBXO32 in cephalic and trunk neural crest lineages. We show that FBXO32 silencing impairs melanocyte proliferation, differentiation, and vascularization. In rescue experiments, co-electroporation with the human wild-type gene compensates for the silencing of the endogenous gene and restores normal melanocyte phenotypes. By contrast, co-electroporation with the human variant, FBXO32G139S, alters melanocyte differentiation, pigment synthesis, triggers migration to the dermis, and favors angiotropism. Transcriptomic analysis reveals targets associated with melanocyte transformation, cytoskeleton remodeling, and focal adhesion. We show that FBXO32 orchestrates unexpected interactions with ASIP for melanogenesis and BAP1 for the post-translational ubiquitination system. We propose FBXO32 as a tumor suppressor gene capable of preventing the onset of pediatric melanoma.

cancer biology↗

bioRxiv2022

B vitamin quantification in lentil seed tissues using ultra-performance liquid chromatography-selected reaction monitoring mass spectrometry

Lentils are an important source of macronutrients, including protein and fiber, as well as micronutrients such as vitamins and minerals, especially in a plant-based diet. Quantifying variation among genotypes, including wild germplasm, is desirable to better understand the genetics of differential B vitamins content for breeding of this trait and to understand their potential contributions to the lentil crop. We analyzed thirty-four cultivated and three wild genotypes for vitamins B1, B2, B3, B5, B6, B7, and B9. Seeds were assayed whole, and separated into cotyledons only, or seed coats only. Variation for all B vitamins was observed across the cultivars. Overall, cotyledons had higher concentrations of B1 and B3, while seed coats had higher concentrations of B2, B5, B6, and B9. Wild accessions had the highest concentrations of vitamin B9 and were also among the highest for vitamin B2. These results demonstrate the differential distribution of B vitamins across seed tissues and lentil genotypes, and that dehulling prior to consumption results in the loss of B vitamins otherwise available in whole seeds. They also indicate there is genetic variability which could be used to increase B-vitamin levels in lentil via breeding.

plant biology↗

bioRxiv2022

INCREASING DIVERSITY AMONG LENS SPECIES FOR IMPROVING BIOLOGICAL NITROGEN FIXATION IN LENTIL

Exotic germplasm is a key resource for reintroducing genetic variability into cultivars. We evaluated 36 accessions from cultivated lentil (Lens culinaris Medik.) and six related wild species, inoculated with a commercial strain of Rhizobium leguminosarum bv. viciae under greenhouse conditions. The objective was to explore Lens species and/or accessions that could contribute higher biological nitrogen fixation (BNF) ability to the lentil crop. A split plot design was used with either Rhizobium inoculation, added Nitrogen (N) or neither, as the main plots, and accessions in subplots randomized in blocks. Two repeats of the experiment were evaluated at flowering for N fixation and nodulation characters, and two subsequent experiments, with a subset of 14 accessions, were evaluated at maturity for seed production, seed quality and harvest index. Differences in phenotypic expression did not correspond to any particular Lens species. CDC Greenstar exhibited some of the highest N fixation values observed among the cultivars and also superior yield results compared to the added N treatment. Wild accessions, including IG 72643 (L. orientalis), displayed unique and multiple desirable characteristics compared to cultivars including indeterminate nodulation, higher N translocation, stable yield compared to added N treatment and exceptionally high protein concentration in seeds.

plant biology↗

bioRxiv2020

Interactions between axon-like projections extended by Drosophila Follicle Stem Cells dictate cell fate decisions

Stem cells cycle between periods of quiescence and proliferation to promote healthy tissue aging. Once proliferation is initiated, mechanisms that control the balance between self-renewal and differentiation must be engaged to ensure maintenance of stem cell pools until the next quiescent cycle occurs. Here, we demonstrate that dynamic axon-like projections extended by Follicle Stem Cells (FSCs) in the Drosophila ovary control the self-renewal-differentiation balance. Known axon growth regulators still life and sickie are necessary and sufficient for FSC projection growth, mediating organization of germline cyst architecture during follicle formation, controlling targeting of projections to FSCs or germ cells, and regulating expression of the cell fate determinants Eyes Absent (Eya) and Castor (Cas). Our results support a model in which FSC projections function similarly to axons, providing structural organization to a dynamic organ while mediating communication between distinct cell types to effect the key cell fate decision to self-renew or differentiate.

developmental biology↗

bioRxiv2020

Dynamics of episodic and continuous rhythmic activities from a developing central pattern generator

Developing spinal motor networks produce a diverse array of outputs, including episodic and continuous patterns of rhythmic activity. Variation in excitability state and neuromodulatory tone can facilitate transitions between episodic and continuous rhythms; however, the intrinsic mechanisms that govern these rhythms and their transitions are poorly understood. Here, we tested the capacity of a single central pattern generator (CPG) circuit with tunable properties to generate multiple outputs. To address this, we deployed a computational model composed of an inhibitory half-centre oscillator (HCO). Following predictions of our computational model, we tested the contributions of key properties to the generation of an episodic rhythm produced by isolated spinal cords of the newborn mouse. The model recapitulates the diverse state-dependent rhythms evoked by dopamine. In the model, episodic bursting depended predominantly on the endogenous oscillatory properties of neurons, with Na+/K+ ATPase pump (IPump) and hyperpolarization-activated currents (Ih) playing key roles. Modulation of either IPumpMax or Ih produced transitions between episodic and continuous rhythms and silence. As IPump increased, the episode duration and period increased along with a reduction in interepisode interval. Increasing Ih increased the episode period along with an increase in episode duration. Pharmacological manipulations of Ih with ZD7288 and IPump with ouabain or monensin in isolated spinal cords produced findings consistent with the model. Our modelling and experimental results highlight key roles of Ih and IPump in producing episodic rhythms and provide insight into mechanisms that permit a single CPG to produce multiple patterns of rhythmicity. Significance statementThe ability of a single CPG to produce and transition between multiple rhythmic patterns of activity is poorly understood. We deployed a complementary computational half-centre oscillator model and an isolated spinal cord experimental preparation to identify key currents whose interaction produced episodic and continuous rhythmic activity. Together, our experimental and modelling approaches suggest mechanisms in spinal networks that govern diverse rhythms and transitions between them. This work sheds light on the ability of a single CPG to produce episodic bouts observed in behavioural and pathological contexts.

neuroscience↗

bioRxiv2019

Development of a Protocol to Study Bronchial Smooth Muscle Cells Behavior on a Natural Biologic Bronchial Matrix

Severe asthma is associated with an increased airway smooth muscle (ASM) mass and an altered composition of the extracellular matrix (ECM). Studies have indicated that ECM-ASM cell interactions contribute to this remodeling and its limited reversibility with current therapy. Three-dimensional matrices allow the study of complex cellular responses to different stimuli in an almost natural environment. Our goal was to obtain acellular bronchial matrices and then develop a recellularization protocol with ASM cells. We studied equine bronchi as horses spontaneously develop a human asthma-like disease. The bronchi were decellularized using Triton/Sodium Deoxycholate. The obtained scaffolds retained their anatomical and histological properties. Using immunohistochemistry and a semi-quantitative score to compare native bronchi to scaffolds revealed no significant variation for matrixial proteins. A DNA quantification and electrophoresis indicated that most of DNA was 29.6 ng/mg of tissue {+/-} 5.6 with remaining fragments of less than 100 bp. Primary ASM cells were seeded on the scaffolds. Histological analysis after recellularization showed that ASM cells migrated and proliferated primarily in the decellularized smooth muscle matrix, suggesting a chemotactic effect of the scaffolds. This is the first report of primary ASM cells preferentially repopulating the smooth muscle matrix layer in bronchial matrices. This protocol is now being used to study the molecular interactions occurring between the asthmatic ECMs and ASM to identify effectors of asthmatic bronchial remodeling.

cell biology↗

bioRxiv2018

Unraveling Tumor-Immune Heterogeneity in Advanced Ovarian Cancer Uncovers Immunogenic Effect of Chemotherapy

In metastatic cancer, the role of heterogeneity at the tumor-immune microenvironment, its molecular underpinnings and clinical relevance remain largely unexplored. To understand tumor-immune dynamics at baseline and upon chemotherapy treatment, we performed unbiased pathway and cell type-specific immunogenomics analysis of treatment-naive (38 samples from 8 patients) and paired chemotherapy treated (80 paired samples from 40 patients) high-grade serous ovarian cancer (HGSOC) samples. Whole transcriptome analysis and image-based quantification of T cells from treatment-naive tumors revealed ubiquitous variability in immune signaling and distinct immune microenvironments co-existing within the same individuals and within tumor deposits at diagnosis. To systematically explore cell type composition of the tumor microenvironment using bulk mRNA, we derived consensus immune and stromal cell gene signatures by intersecting state-of-the-art deconvolution methods, providing improved accuracy and sensitivity when compared to HGSOC immunostaining and leukocyte methylation data sets. Cell-type deconvolution and pathway analyses revealed that Myc and Wnt signaling associate with immune cell exclusion in untreated HGSOC. To evaluate the effect of chemotherapy on the intrinsic tumor-immune heterogeneity, we compared site-matched and site-unmatched tumors before and after neoadjuvant chemotherapy. Transcriptomic and T-cell receptor sequencing analyses showed that site-matched samples had increased cytotoxic immune activation and oligoclonal expansion of T cells after chemotherapy, which was not seen in site-unmatched samples where heterogeneity could not be accounted for. These results demonstrate that the tumor-immune interface in advanced HGSOC is intrinsically heterogeneous, and thus requires site-specific analysis to reliably unmask the impact of therapy on the tumor-immune microenvironment.

cancer biology↗