Biology subjects

Rodriguez, A.

Publications and source records attributed to Rodriguez, A..

At least 91 records · Page 5Linked to original sources

bioRxiv2020

Discovery of the first selective M4 muscarinic acetylcholine receptor antagonists with in vivo anti-parkinsonian and anti-dystonic efficacy

Non-selective antagonists of muscarinic acetylcholine receptors (mAChRs) that broadly inhibit all five mAChR subtypes provide an efficacious treatment for some movement disorders, including Parkinson disease and dystonia. Despite their efficacy in these and other central nervous system disorders, anti-muscarinic therapy has limited utility due to severe adverse effects that often limit their tolerability by patients. Recent advances in understanding the roles that each mAChR subtype plays in disease pathology suggest that highly selective ligands for individual subtypes may underlie the anti-parkinsonian and anti-dystonic efficacy observed with the use of non-selective anti-muscarinic therapeutics. Our recent work has indicated that the M4 muscarinic acetylcholine receptor has several important roles in opposing aberrant neurotransmitter release, intracellular signaling pathways, and brain circuits associated with movement disorders. This raises the possibility that selective antagonists of M4 may recapitulate the efficacy of non-selective anti-muscarinic therapeutics and may decrease or eliminate the adverse effects associated with these drugs. However, this has not been directly tested due to lack of selective antagonists of M4. Here we utilize genetic mAChR knockout animals in combination with non-selective mAChR antagonists to confirm that the M4 receptor underlies the locomotor-stimulating and anti-parkinsonian efficacy in rodent models. We also report the synthesis, discovery, and characterization of the first-in-class selective M4 antagonists VU6013720, VU6021302, and VU6021625 and confirm that these optimized compounds have anti-parkinsonian and anti-dystonic efficacy in pharmacological and genetic models of movement disorders.

pharmacology and toxicology↗

bioRxiv2020

Helicobacter pylori accelerates KRAS-dependent gastric dysplasia

More than 80% of gastric cancer is attributable to stomach infection with Helicobacter pylori (Hp), even though the bacterium is not always present at time of diagnosis. Infection is thought to lead to cancer by promoting the accumulation of oncogenic mutations downstream of inflammation; once oncogenic pathways become activated, infection may become dispensable for cancer development. Gastric preneoplastic progression involves sequential changes to the tissue, including loss of parietal cells, spasmolytic polypeptide-expressing metaplasia (SPEM), intestinal metaplasia (IM) and dysplasia. In mice, active KRAS expression recapitulates these tissue changes in the absence of Hp infection. This model provides an experimental system to investigate whether Hp infection has additional roles in preneoplastic progression, beyond initiating inflammation. Mice were assessed by evaluating tissue histology, gene expression changes, the immune cell repertoire, and expression of metaplasia and dysplasia markers. Compared to Hp-/KRAS+ mice, Hp+/KRAS+ mice had i) severe T cell infiltration and altered macrophage polarization; ii) altered expression of metaplasia markers, including increased expression of CD44v9 (SPEM) and decreased expression of TFF3 (IM); iii) more dysplastic (TROP2+) glands; and iv) greater proliferation of metaplastic and dysplastic glands. Hp was able to persistently colonize the stomach during the onset of these tissue changes, and eradication of Hp with antibiotics prevented metaplastic, dysplastic and proliferation marker changes. Collectively, these results suggest that gastric preneoplastic progression differs between Hp+ and Hp-cases, and that sustained Hp infection can promote the later stages of gastric preneoplastic progression, in addition to its established role in initiating chronic inflammation.

cancer biology↗

bioRxiv2020

A comprehensive, FAIR file format for neuroanatomical structure modeling

With advances in microscopy and computer science, the technique of digitally reconstructing, modeling, and quantifying microscopic anatomies has become central to many fields of biological research. MBF Bioscience has chosen to openly document their digital reconstruction file format, Neuromorphological File Specification (4.0), available at www.mbfbioscience.com/filespecification (Angstman et al. 2020). One of such technologies, the format created and maintained by MBF Bioscience is broadly utilized by the neuroscience community. The data formats structure and capabilities have evolved since its inception, with modifications made to keep pace with advancements in microscopy and the scientific questions raised by worldwide experts in the field. More recent modifications to the neuromorphological data format ensure it abides by the Findable, Accessible, Interoperable, and Reusable (FAIR) data standards promoted by the International Neuroinformatics Coordinating Facility (INCF; Wilkinson et al. 2016). The incorporated metadata make it easy to identify and repurpose these data types for downstream application and investigation. This publication describes key elements of the file format and details their relevant structural advantages in an effort to encourage the reuse of these rich data files for alternative analysis or reproduction of derived conclusions.

neuroscience↗

bioRxiv2020

Inoculation with highly-related mycorrhizal fungal siblings, and their interaction with plant genoptypes, strongly shapes tropical mycorrhizal fungal community structure

Arbuscular mycorrhizal fungi (AMF) have the potential to increase crop yields and all globally important crops form the mycorrhizal symbiosis. Only a few studies have investigated the impact of introduced AMF on local AMF communities and most studies have only investigated effects of one isolate. We studied the impact on AMF community structure of inoculating roots of the globally important crop cassava with highly genetically-related clonal siblings of two genetically different Rhizophagus irregularis isolates. We hypothesized that inoculation with R. irregularis siblings differentially influences the structure and the diversity of the pre-existing AMF community colonizing cassava. Alpha and beta taxonomic and phylogenetic AMF diversity were strongly and significantly altered differentially following inoculation with sibling AMF progeny. In most cases, the effects were also cassava-genotype specific. Although biomass production and AMF colonization were also both differentially affected by inoculation with sibling R. irregularis progeny these variables were not correlated with changes in the AMF community structure. The results highlight that investigations on the impact of an introduced AMF species, that use only one isolate, are unlikely to be representative of the overall effects of that AMF species and that the genetic identity of the host must be considered. The amount of inoculum added was very small and effects were observed 12 months following inoculation. That such a small amount of almost genetically identical fungal inoculum can strongly differentially influence AMF community structure 12 months following inoculation, indicates that AMF communities in tropical soils are not very resistant to perturbation.

ecology↗

bioRxiv2020

The Genomic Landscape of Prostate Cancer Brain Metastases

Lethal prostate cancer commonly metastasizes to bone, lymph nodes, and visceral organs but with more effective therapies, there is an increased frequency of metastases to the brain. Little is known about the genomic drivers of prostate cancer brain metastases (PCBM). To address this, we conducted a comprehensive multi-regional, genomic, and targeted transcriptomic analysis of PCBM from 28 patients. We compared whole-exome and targeted RNA sequencing with matched primary tumors when available (n = 10) and with publicly available genomic data from non-brain prostate cancer metastases (n = 416). In addition to common alterations in TP53, AR, RB1, and PTEN, we identified highly significant enrichment of mutations in NF1 (25% cases (6/28), q = 0.049, 95% CI = 2.38 - 26.52, OR = 8.37) and RICTOR (17.9% cases (5/28), q = 0.01, 95% CI = 6.74 - 480.15, OR = 43.7) in PCBM compared to non-brain prostate cancer metastases, suggesting possible activation of the druggable pathways RAS/RAF/MEK/ERK and PI3K/AKT/mTOR, respectively. Compared to non-brain prostate cancer metastases, PCBM were almost three times as likely to harbor DNA homologous repair (HR) alterations (42.9% cases (12/28), p =0.016, 95% CI = 1.17 - 6.64, OR = 2.8). When considering the combination of somatic mutations, copy number alteration, and Large-scale State Transitions, 64.3% of patients (18/28) were affected. HR alterations may be critical drivers of brain metastasis that potentially provide cancer cells a survival advantage during re-establishment in a special microenvironment. We demonstrate that PCBM have genomic dependencies that may be exploitable through clinical interventions including PARP inhibition.

cancer biology↗

bioRxiv2020

Pancreatic beta-cell specific deletion of VPS41 causes diabetes due to defects in insulin secretion

Insulin secretory granules (SGs) mediate the regulated secretion of insulin, which is essential for glucose homeostasis. The basic machinery responsible for this regulated exocytosis consists of specific proteins present both at the plasma membrane and on insulin SGs. The protein composition of insulin SGs thus dictates their release properties, yet the mechanisms controlling insulin SG formation, which determines this molecular composition, remain poorly understood. VPS41, a component of the endo-lysosomal tethering HOPS complex, was recently identified as a cytosolic factor involved in the formation of neuroendocrine and neuronal granules. We now find that VPS41 is required for insulin SG biogenesis and regulated insulin secretion. Loss of VPS41 in pancreatic {beta}-cells leads to a reduction in insulin SG number, changes in their transmembrane protein composition, and defects in granule regulated exocytosis. Exploring a human point mutation, identified in patients with neurological but no endocrine defects, we show that the effect on SG formation is independent of HOPS complex formation. Finally, we report that mice with a deletion of VPS41 specifically in {beta}-cells develop diabetes due to severe depletion of insulin SG content and a defect in insulin secretion. In sum, our data demonstrate that VPS41 contributes to glucose homeostasis and metabolism.

physiology↗

bioRxiv2020

Achromatic body markings as a widespread visual mechanism across group living animals

Grouping is a widespread form of predator defense, with individuals in groups often performing evasive collective movements in response to predators attacks. Individuals in these groups use behavioral rules to coordinate their movements, with visual cues about neighbors positions and orientations informing movement decisions. Although the exact visual cues individuals use to coordinate their movements with neighbors have not yet been decoded, some studies have suggested that stripes, lines or other body patterns may act as conspicuous conveyors of movement information that could promote coordinated group movement, or promote dazzle camouflage, thereby confusing predators. We used phylogenetic logistic regressions to test whether the contrasting achromatic stripes present in four different taxa vulnerable to predation, including species within two orders of birds (Anseriformes and Charadriiformes), a suborder of Artiodactyla (the ruminants) and several orders of marine fish (predominantly Perciformes) were associated with group living. Contrasting patterns were significantly more prevalent in social species, and tended to be absent in solitary species or species less vulnerable to predation. We suggest that stripes taking the form of light-colored lines on dark backgrounds, or vice versa, provide a widespread mechanism across taxa that serves either to inform conspecifics of neighbors directional movement, or to confuse predators, when moving in groups. Detection and processing of patterns and of motion in the visual channel is essentially colourblind. That diverse animal taxa with widely different vision systems (including di-, tri- and tetrachromats) appear to have converged on a similar use of achromatic patterns is therefore expected given signal-detection theory. This hypothesis would explain the convergent evolution of conspicuous achromatic patterns as an antipredator mechanism in numerous vertebrate species.

evolutionary biology↗

bioRxiv2020

Innovation, conservation and repurposing of gene function in plant root cell type development

Plant species have evolved myriads of solutions to adapt to dynamic environments, including complex cell type development and regulation. To understand this diversity, we profiled tomato root cell type translatomes and chromatin accessibility. Using xylem differentiation in tomato, relative to Arabidopsis, examples of functional innovation, repurposing and conservation of transcription factors are described. Repurposing and innovation of genes are further observed within an exodermis regulatory network and illustrate its function. Translatome analyses of rice, tomato and Arabidopsis tissues suggest that root meristems are more conserved, and that the functions of constitutively expressed genes are more conserved than those of cell type/tissue-enriched genes. These observations suggest that higher-order properties of cell type and pan-cell type regulation are conserved between plants and animals. One Sentence SummaryPan-species cell type translatome and chromatin accessibility data reveal novelty, conservation and repurposing of gene function.

genomics↗

bioRxiv2020

Analysis of computational codon usage models and their association with translationally slow codons

Improved computational modeling of protein translation rates, including better prediction of where translational slowdowns along an mRNA sequence may occur, is critical for understanding co-translational folding. Because codons within a synonymous codon group are translated at different rates, many computational translation models rely on analyzing synonymous codons. Some models rely on genome-wide codon usage bias (CUB), believing that globally rare and common codons are the most informative of slow and fast translation, respectively. Others use the CUB observed only in highly expressed genes, which should be under selective pressure to be translated efficiently (and whose CUB may therefore be more indicative of translation rates). No prior work has analyzed these models for their ability to predict translational slowdowns. Here, we evaluate five models for their association with slowly translated positions as denoted by two independent ribosome footprint (RFP) count experiments from S. cerevisiae, because RFP data is often considered as a "ground truth" for translation rates across mRNA sequences. We show that all five considered models strongly associate with the RFP data and therefore have potential for estimating translational slowdowns. However, we also show that there is a weak correlation between RFP counts for the same genes originating from independent experiments, even when their experimental conditions are similar. This raises concerns about the efficacy of using current RFP experimental data for estimating translation rates and highlights a potential advantage of using computational models to understand translation rates instead.

bioinformatics↗

bioRxiv2020

The immune response and microbiota profiles during co-infection with P. vivax and soil-transmitted helminths

Co-infection with soil-transmitted helminths (STH) and Plasmodium spp. parasites is a common occurrence in tropical low-income countries, but the consequences of this interaction remain poorly understood. Here, we performed a multi-omic analysis on peripheral blood and fecal samples from 130 individuals in Tierralta, Cordoba, Colombia who were infected with P. vivax alone (n = 33), co-infected with P. vivax and STH (n = 27), infected with STH alone (n = 39) or were infected with neither P. vivax nor STH (n = 31). In addition to Complete Blood Count (CBC) with differential, transcriptional profiling of peripheral blood samples was performed by RNA-Seq, fecal microbial communities were determined by 16S ribosomal RNA gene sequencing and circulating cytokine levels were measured by bead-based immunoassays. Differences in blood cell counts were driven primarily by P. vivax infection, including an increased percentage of neutrophils that was associated with a transcriptional signature of neutrophil activation in the blood. P. vivax infection was also associated with increased levels of IL-6, IL-8 and IL-10, and these cytokine levels were not affected by STH co-infection. Surprisingly, P. vivax infection was more strongly associated with changes in the microbiome than STH infection. Children infected with P. vivax exhibited elevated Bacteroides and reduced Prevotella and Clostridiaceae, but these differences were not observed in individuals co-infected with STH. We also observed that P. vivax parasitemia was higher in the STH-infected population. When we used machine learning to identify the most important predictors of P. vivax parasite burden from all measured variables, bacterial taxa were the strongest predictors of parasitemia levels. In contrast, circulating TGF-{beta} was the strongest predictor of T. trichiura egg burden. This study provides unexpected evidence that the gut microbiota may have a stronger link with P. vivax than with STH infection.

microbiology↗

bioRxiv2019

Unraveling nanotopography of cell surface receptors

Cells communicate with their environment via surface receptors, but nanoscopic receptor organization with respect to complex cell surface morphology remains unclear. This is mainly due to a lack of accessible, robust and high-resolution methods. Here, we present an approach for mapping the topography of receptors at the cell surface with nanometer precision. The method involves coating glass coverslips with glycine, which preserves the fine membrane morphology while allowing immobilized cells to be positioned close to the optical surface. We developed an advanced and simplified algorithm for the analysis of single-molecule localization data acquired in a biplane detection scheme. These advancements enable direct and quantitative mapping of protein distribution on ruffled plasma membranes with near isotropic 3D nanometer resolution. As demonstrated successfully for CD4 and CD45 receptors, the described workflow is a straightforward quantitative technique to study molecules and their interactions at the complex surface nanomorphology of differentiated metazoan cells.

cell biology↗

bioRxiv2019

Using variation in arbuscular mycorrhizal fungi to drive the productivity of the food security crop cassava

The unprecedented challenge to feed the rapidly growing human population can only be achieved with major changes in how we combine technology with agronomy1. Despite their potential few beneficial microbes have truly been demonstrated to significantly increase productivity of globally important crops in real farming conditions2,3. The way microbes are employed has largely ignored the successes of crop breeding where naturally occurring intraspecific variation of plants has been used to increase yields. Doing this with microbes requires establishing a link between variation in the microbes and quantitative traits of crop growth along with a clear demonstration that intraspecific microbial variation can potentially lead to large differences in crop productivity in real farming conditions. Arbuscular mycorrhizal fungi (AMF), form symbioses with globally important crops and show great potential to improve crop yields2. Here we demonstrate the first link between patterns of genome-wide intraspecific AMF variation and productivity of the globally important food crop cassava. Cassava, one of the most important food security crops, feeds approximately 800 million people daily4. In subsequent field trials, inoculation with genetically different isolates of the AMF Rhizophagus irregularis altered cassava root productivity by up to 1.46-fold in conventional cultivation in Colombia. In independent field trials in Colombia, Kenya and Tanzania, clonal sibling progeny of homokaryon and dikaryon parental AMF enormously altered cassava root productivity by up to 3 kg per plant and up to a 3.69-fold productivity difference. Siblings were clonal and, thus, qualitatively genetically identical. Heterokaryon siblings can vary quantitatively but monokaryon siblings are identical. Very large among-AMF sibling effects were observed at each location although which sibling AMF was most effective depended strongly on location and cassava variety. We demonstrate the enormous potential of genetic, and possibly epigenetic variation, in AMF to greatly alter productivity of a globally important crop that should not be ignored. A microbial improvement program to accelerate crop yield increases over that possible by plant breeding or GMO technology alone is feasible. However, such a paradigm shift can only be realised if researchers address how plant genetics and local environments affect mycorrhizal responsiveness of crops to predict which fungal variant will be effective in a given location.

microbiology↗

bioRxiv2019

Effects of mesotocin on social bonding in pinyon jays

The neuropeptide oxytocin influences mammalian social bonding by facilitating the building and maintenance of parental, sexual, and same-sex social relationships. However, we do not know whether the function of the avian homologue mesotocin is evolutionarily conserved across birds. While it does influence avian prosocial behavior, mesotocins role in avian social bonding remains unclear. Here, we investigated whether mesotocin regulates the formation and maintenance of same-sex social bonding in pinyon jays (Gymnorhinus cyanocephalus), a member of the crow family. We formed squads of four individually housed birds. In the first, pair-formation phase of the experiment, we repeatedly placed pairs of birds from within the squad together in a cage for short periods of time. Prior to entering the cage, we intranasally administered one of three hormone solutions to both members of the pair: mesotocin, oxytocin antagonist, or saline. Pairs received repeated sessions with administration of the same hormone. In the second, pair-maintenance phase of the experiment, all four members of the squad were placed together in a large cage, and no hormones were administered. For both phases, we measured the physical proximity between pairs as our proxy for social bonding. We found that, compared to saline, administering mesotocin or oxytocin antagonist did not result in different proximities in either the pair-formation or pair-maintenance phase of the experiment. Therefore, at the dosages and time frames used here, exogenously introduced mesotocin did not influence same-sex social bond formation or maintenance. Like oxytocin in mammals, mesotocin regulates avian prosocial behavior; however, unlike oxytocin, we do not have evidence that mesotocin regulates social bonds in birds.

animal behavior and cognition↗

bioRxiv2018

DNA methylation links prenatal smoking exposure to later life health outcomes in offspring.

Maternal smoking during pregnancy is associated with adverse offspring health outcomes across their life course. We hypothesize that DNA methylation is a potential mediator of this relationship. To test this, we examined the association of prenatal maternal smoking with DNA methylation in 2,821 individuals (age 16 to 48 years) from five prospective birth cohort studies and perform Mendelian randomization and mediation analyses to assess, whether methylation markers have causal effects on disease outcomes in the offspring. We identify 69 differentially methylated CpGs in 36 genomic regions (P < 1x10-7), and show that DNA methylation may represent a biological mechanism through which maternal smoking is associated with increased risk of psychiatric morbidity in the exposed offspring.

epidemiology↗

bioRxiv2018

Cortical Column and Whole Brain Imaging of Neural Circuits with Molecular Contrast and Nanoscale Resolution

Optical and electron microscopy have made tremendous inroads in understanding the complexity of the brain, but the former offers insufficient resolution to reveal subcellular details and the latter lacks the throughput and molecular contrast to visualize specific molecular constituents over mm-scale or larger dimensions. We combined expansion microscopy and lattice light sheet microscopy to image the nanoscale spatial relationships between proteins across the thickness of the mouse cortex or the entire Drosophila brain, including synaptic proteins at dendritic spines, myelination along axons, and presynaptic densities at dopaminergic neurons in every fly neuropil domain. The technology should enable statistically rich, large scale studies of neural development, sexual dimorphism, degree of stereotypy, and structural correlations to behavior or neural activity, all with molecular contrast.\n\nOne Sentence SummaryCombined expansion and lattice light sheet microscopy enables high speed, nanoscale molecular imaging of neural circuits over large volumes.

neuroscience↗

bioRxiv2018

Intracellular calcium dysregulation precedes muscle decline in C. elegans modeling Duchenne muscular dystrophy

Duchenne muscular dystrophy (DMD) is a genetic disorder caused by loss of the protein dystrophin. In humans, DMD has early onset, causes developmental delays, muscle necrosis, loss of ambulation, and early death. Current animal models have been challenged by their inability to model the early onset and severity of the disease. Thus it remains unresolved if increased sarcoplasmic calcium observed in dystrophic muscles follows or leads the mechanical insults caused by the muscles disrupted contractile machinery. This knowledge has important applications for patients, as potential physiotherapeutic treatments may either help or exacerbate symptoms, depending on how dystrophic muscles differ from healthy ones. Recently we showed how burrowing dystrophic (dys-1) C. elegans recapitulate many salient phenotypes of DMD, including loss of mobility and muscle necrosis. Here we report dys-1 worms display early pathogenesis, including dysregulated sarcoplasmic calcium, and increased lethality. Sarcoplasmic calcium dysregulation in dys-1 worms precedes overt structural phenotypes (e.g. mitochondrial, and contractile machinery damage) and can be mitigated by silencing calmodulin expression. To learn how dystrophic musculature responds to altered physical activity, we cultivated dys-1 animals in environments requiring high amplitude, or high frequency of muscle exertion during locomotion. We find that several muscular parameters (such as size) improve with increased activity. However, longevity in dystrophic animals was negatively associated with muscular exertion, regardless of the duration of the effort. The high degree of phenotypic conservation between dystrophic worms and humans provides a unique opportunity to gain insights into the etiology of the disease, as well as the initial assessment of potential treatment strategies.\n\nSIGNIFICANCEDuchenne muscular dystrophy is a degenerative disease affecting tens of thousands of people in the US alone. Much remains unknown about the disease, including the chain of events that links the loss of dystrophin to muscle death, or the extent to which exercise might be able to protect degenerating muscles. We used the nematode C. elegans to show that sarcoplasmic calcium dysregulation takes place in dystrophic muscles long before other overt signs of damage manifest. When placed in assays that altered muscular activity by increasing either contraction frequency or amplitude, we observed several metrics associated with muscular repair increase. However, no treatment positively affected the life expectancy of dystrophic animals.

molecular biology↗

bioRxiv2018

Xanthine urolithiasis: Inhibitors of xanthine crystallization

OBJECTIVETo identify in vitro inhibitors of xanthine crystallization that have potential for inhibiting the formation of xanthine crystals in urine and preventing the development of the renal calculi in patients with xanthinuria.\n\nMETHODSThe formation of xanthine crystals in synthetic urine and the effects of 10 potential crystallization inhibitors were assessed using a kinetic turbidimetric system with a photometer. The maximum concentration tested for each compound was: 20 mg/L for 3-methylxanthine (3-MX); 40 mg/L for 7-methylxanthine (7-MX), 1- methylxanthine (1-MX), theobromine (TB), theophylline, paraxanthine, and caffeine; 45 mg/L for 1-methyluric acid; 80 mg/L for 1,3-dimethyluric acid; and 200 mg/L for hypoxanthine. All crystals were examined by scanning electron microscopy.\n\nRESULTSOnly 7-MX, 3-MX, and 1-MX significantly inhibited xanthine crystallization at the tested concentrations. Mixtures of inhibitors had an additive effect rather than a synergistic effect on crystallization.\n\nCONCLUSIONTwo of the inhibitors identified here --7-MX and 3-MX -- are major metabolites of TB. In particular, after TB consumption, 20% is excreted in the urine as TB, 21.5% as 3-MX, and 36 % as 7-MX. Thus, consumption of theobromine could protect patients with xanthinuria from the development of renal xanthine calculi. Clinical trials are necessary to demonstrate these effects in vivo.

pharmacology and toxicology↗

bioRxiv2018

Reproducible big data science: A case study in continuous FAIRness

Big biomedical data create exciting opportunities for discovery, but make it difficult to capture analyses and outputs in forms that are findable, accessible, interoperable, and reusable (FAIR). In response, we describe tools that make it easy to capture, and assign identifiers to, data and code throughout the data lifecycle. We illustrate the use of these tools via a case study involving a multi-step analysis that creates an atlas of putative transcription factor binding sites from terabytes of ENCODE DNase I hypersensitive sites sequencing data. We show how the tools automate routine but complex tasks, capture analysis algorithms in understandable and reusable forms, and harness fast networks and powerful cloud computers to process data rapidly, all without sacrificing usability or reproducibility--thus ensuring that big data are not hard-to-(re)use data. We compare and contrast our approach with other approaches to big data analysis and reproducibility.

bioinformatics↗