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Register a new userComputational diagnosis and risk evaluation for canine lymphoma
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The canine lymphoma blood test detects the levels of two biomarkers, the acute phase proteins (C-Reactive Protein and Haptoglobin). This test can be used for diagnostics, for screening, and for remission monitoring as well. We analyze clinical data, test various machine learning methods and select the best approach to these problems. Three family of methods, decision trees, kNN (including advanced and adaptive kNN) and probability density evaluation with radial basis functions, are used for classification and risk estimation. Several pre-processing approaches were implemented and compared. The best of them are used to create the diagnostic system. For the differential diagnosis the best solution gives the sensitivity and specificity of 83.5% and 77%, respectively (using three input features, CRP, Haptoglobin and standard clinical symptom). For the screening task, the decision tree method provides the best result, with sensitivity and specificity of 81.4% and >99%, respectively (using the same input features). If the clinical symptoms (Lymphadenopathy) are considered as unknown then a decision tree with CRP and Hapt only provides sensitivity 69% and specificity 83.5%. The lymphoma risk evaluation problem is formulated and solved. The best models are selected as the system for computational lymphoma diagnosis and evaluation the risk of lymphoma as well. These methods are implemented into a special web-accessed software and are applied to problem of monitoring dogs with lymphoma after treatment. It detects recurrence of lymphoma up to two months prior to the appearance of clinical signs. The risk map visualisation provides a friendly tool for explanatory data analysis.
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In computational biology and other sciences, researchers are frequently faced with a choice between several computational methods for performing data analyses. Benchmarking studies aim to rigorously compare the performance of different methods using well-characterized benchmark datasets, to determine the strengths of each method or to provide recommendations regarding suitable choices of methods for an analysis. However, benchmarking studies must be carefully designed and implemented to provide accurate, unbiased, and informative results. Here, we summarize key practical guidelines and recommendations for performing high-quality benchmarking analyses, based on our experiences in computational biology.
A biological experiment is the most reliable way of assigning function to a protein. However, in the era of high-throughput sequencing, scientists are unable to carry out experiments to determine the function of every single gene product. Therefore, to gain insights into the activity of these molecules and guide experiments, we must rely on computational means to functionally annotate the majority of sequence data. To understand how well these algorithms perform, we have established a challenge involving a broad scientific community in which we evaluate different annotation methods according to their ability to predict the associations between previously unannotated protein sequences and Gene Ontology terms. Here we discuss the rationale, benefits and issues associated with evaluating computational methods in an ongoing community-wide challenge.
Objective: This study illustrates the ambiguity of ROC in evaluating two classifiers of 90-day LVAD mortality. This paper also introduces the precision recall curve (PRC) as a supplemental metric that is more representative of LVAD classifiers performance in predicting the minority class. Background: In the LVAD domain, the receiver operating characteristic (ROC) is a commonly applied metric of performance of classifiers. However, ROC can provide a distorted view of classifiers ability to predict short-term mortality due to the overwhelmingly greater proportion of patients who survive, i.e. imbalanced data. Methods: This study compared the ROC and PRC for the outcome of two classifiers for 90-day LVAD mortality for 800 patients (test group) recorded in INTERMACS who received a continuous-flow LVAD between 2006 and 2016 (mean age of 59 years; 146 females vs. 654 males) in which mortality rate is only %8 at 90-day (imbalanced data). The two classifiers were HeartMate Risk Score (HMRS) and a Random Forest (RF). Results: The ROC indicates fairly good performance of RF and HRMS classifiers with Area Under Curves (AUC) of 0.77 vs. 0.63, respectively. This is in contrast with their PRC with AUC of 0.43 vs. 0.16 for RF and HRMS, respectively. The PRC for HRMS showed the precision rapidly dropped to only 10% with slightly increasing sensitivity. Conclusion: The ROC can portray an overly-optimistic performance of a classifier or risk score when applied to imbalanced data. The PRC provides better insight about the performance of a classifier by focusing on the minority class.
Objectives: Current standards for comparing stunting across human populations assume a universal model of child growth. Such comparisons ignore population differences that are independent of deprivation and health outcomes. This paper partitions variation in height-for-age that is specifically associated with deprivation and health outcomes to provide a basis for cross-population comparisons. Materials & Methods: Using a multi-level model with a sigmoid relationship of resources and growth, we partition variation in height-for-age z-scores (HAZ) from 1,522,564 children across 70 countries into two components: 1) accrued HAZ shaped by environmental inputs (e.g., undernutrition, infectious disease, inadequate sanitation, poverty), and 2) a country-specific basal HAZ independent of such inputs. We validate these components against population-level infant mortality rates, and assess how these basal differences may affect cross-population comparisons of stunting. Results: Basal HAZ differs reliably across countries (range of 1.5 SD) and is independent of measures of infant mortality. By contrast, accrued HAZ captures stunting as impaired growth due to deprivation and is more closely associated with infant mortality than observed HAZ. Ranking populations by accrued HAZ suggest that populations in West Africa and the Caribbean suffer much greater levels of stunting than suggested by observed HAZ. Discussion: Current universal standards may dramatically underestimate stunting in populations with taller basal HAZ. Relying on observed HAZ rather than accrued HAZ may also lead to inappropriate cross-population comparisons, such as concluding that Haitian children enjoy better conditions for growth than do Indian or Guatemalan children.
High-throughput metabolomics investigations, when conducted in large human cohorts, represent a potentially powerful tool for elucidating the biochemical diversity and mechanisms underlying human health and disease. Large-scale metabolomics data, generated using targeted or nontargeted platforms, are increasingly more common. Appropriate statistical analysis of these complex high-dimensional data is critical for extracting meaningful results from such large-scale human metabolomics studies. Herein, we consider the main statistical analytical approaches that have been employed in human metabolomics studies. Based on the lessons learned and collective experience to date in the field, we propose a step-by-step framework for pursuing statistical analyses of human metabolomics data. We discuss the range of options and potential approaches that may be employed at each stage of data management, analysis, and interpretation, and offer guidance on analytical considerations that are important for implementing an analysis workflow. Certain pervasive analytical challenges facing human metabolomics warrant ongoing research. Addressing these challenges will allow for more standardization in the field and lead to analytical advances in metabolomics investigations with the potential to elucidate novel mechanisms underlying human health and disease.
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