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Biology subjects

Ortega, L.

Publications and source records attributed to Ortega, L..

3 recordsLinked to original sources

Bench-ML: A Benchmarking Web Interface for Machine Learning Methods and Models in Genomics

Machine learning is a complex but essential technology in genomics data analysis and its popularity has increased the rate of new methodological approaches published but this raises the question of how models should be benchmarked and validated. Bench-ML is a generalizable and easy to use web interface for benchmarking and validation that can preprocess data, train, test, evaluate and compare machine learning algorithms for genomics. It makes benchmarking machine learning methods more accessible by enabling genomics scientists to perform end-to-end analyses, visualize results and evaluate performance or metrics to compare methods and models by providing a point of reference using only a web browser. To improve something it needs to be measured; To benchmark and evaluate models Bench-ML provides several strategies, methodologies, and tools to generate measurements and visualizations to track experiments to help identify areas of opportunity using metrics such as loss and accuracy, model visualization, learning and saturation curves, principal component analysis, feature scoring, confusion matrix, regression for training and test data, mean absolute error, etc. Bench-ML explains the different options to test and validate machine and deep learning models to identify problematic areas and potentially improve performance. Bench-ML provides several strategies to improve performance like showing when a model is not performing or when different hyperparameters values could be needed, it also helps fine tune hyperparameter values and to identify accuracy across multiple classes and from these classes which class could affect performance. The selection, development, and comparison of machine learning methods and models in genomics datasets can be a daunting task based on the goals of a particular study or the target problem. Machine learning is very good at pattern recognition but modeling the world is much more than that so how to know if a machine learning method or model is performing at a good sensitivity and specificity in large genomics datasets is still a big problem and this is where Bench-ML can help.

bioinformatics↗

Non-intravenous, carbapenem-sparing antibiotics for the treatment of bacteremia due to ESBL or AMP-C β-lactamase: A propensity score study

IntroductionCarbapenems are considered the treatment of choice for extended-spectrum {beta}-lactamase (ESBL) or Amp-C {beta}-lactamase-producing Enterobacteriaceae bacteremia. Data on the effectiveness of non-intravenous carbapenem-sparing antibiotic options are limited.\n\nObjectiveTo compare the 30 day-mortality and clinical failures associated with the use of carbapenems vs an alternative non-intravenous antibiotic for the definitive treatment of ESBL/Amp-C positive Enterobacteriaceae bacteremia.\n\nMethodsThis is a 12-year retrospective study (2004 - 2015) including all patients with bacteremia due to ESBL/Amp-C-producing Enterobacteriaceae. Given the lack of randomization of the initial therapies, a propensity score for receiving carbapenems was calculated.\n\nResultsThere were 1115 patients with a first episode of bacteremia due to E. coli or K. pneumoniae, of which 123 were ESBL/Amp C-positive (11%). There were 101 eligible patients: 59 in the carbapenem group and 42 in the alternative treatment group (cotrimoxazole 59.5%, quinolones 21.4%). The most frequent sources of infection were urinary (63%) and biliary (15%). Compared to the carbapenem group, patients treated with the alternative regimen had a shorter hospital stay (median [IQR]: 7 days [5-10] vs 12 days [9-18], p<0,001). The use of an alternative non-IV treatment did not increase mortality (OR 27; 95% CI 0.05-1.61; p=.15). After controlling for confounding factors with the propensity score, the adjusted OR of carbapenem treatment was 4.95; 95% CI (0.9426.01, p=.059).\n\nConclusionAlternative non-IV carbapenem-sparing antibiotics could have a role in the definitive treatment of ESBL/Amp-C-positive Enterobacteriaceae bloodstream infections, allowing a reduction in carbapenem use. The use of cotrimoxazole in this setting has shown favourable results.\n\nSome of the data contained in this article were presented at the 55th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) and at the 28th International Congress of Chemotherapy Meeting (ICC), San Diego, USA, 2015.

pathology↗

QTL mapping of natural variation reveals that the developmental regulator bruno reduces tolerance to P-element transposition in the Drosophila female germline

Transposable elements (TEs) are obligate genetic parasites that propagate in host genomes by replicating in germline nuclei, thereby ensuring transmission to offspring. This selfish replication not only produces deleterious mutations---in extreme cases, TE mobilization induces genotoxic stress that prohibits the production of viable gametes. Host genomes could reduce these fitness effects in two ways: resistance and tolerance. Resistance to TE propagation is enacted by germline specific small-RNA-mediated silencing pathways, such as the piRNA pathway, and is studied extensively. However, it remains entirely unknown whether host genomes may also evolve tolerance, by desensitizing gametogenesis to the harmful effects of TEs. In part, the absence of research on tolerance reflects a lack of opportunity, as small-RNA-mediated silencing evolves rapidly after a new TE invades, thereby masking existing variation in tolerance.\n\nWe have exploited the recent the historical invasion of the Drosophila melanogaster genome by P-element DNA transposons in order to study tolerance of TE activity. In the absence of piRNA-mediated silencing, the genotoxic stress imposed by P-elements disrupts oogenesis, and in extreme cases leads to atrophied ovaries that completely lack germline cells. By performing QTL-mapping on a panel of recombinant inbred lines (RILs) that lack piRNA-mediated silencing of P- elements, we uncovered multiple QTL that are associated with differences in tolerance of oogenesis to P-element transposition. We localized the most significant QTL to a small 230 Kb euchromatic region, with the LOD peak occurring in the Bruno locus, which codes for a critical and well-studied developmental regulator of oogenesis. We further demonstrate that multiple bruno loss-of-function alleles are strong dominant suppressors of ovarian atrophy, allowing for the development of mature egg-chambers in the face of P-element activity. Genetic and cytological analyses suggest that bruno tolerance is explained by enhanced retention of germline stem cells in dysgenic ovaries, which are typically lost due to DNA damage. Our observations reveal segregating variation in TE tolerance for the first time, and implicate gametogenic regulators as a source of tolerant variants in natural populations.

genetics↗