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تسجيل مستخدم جديدClassification and Visualization of Genotype x Phenotype Interactions in Biomass Sorghum
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We introduce a simple approach to understanding the relationship between single nucleotide polymorphisms (SNPs), or groups of related SNPs, and the phenotypes they control. The pipeline involves training deep convolutional neural networks (CNNs) to differentiate between images of plants with reference and alterna
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Hypertension is a heterogeneous syndrome in need of improved subtyping using phenotypic and genetic measurements so that patients in different subtypes share similar pathophysiologic mechanisms and respond more uniformly to targeted treatments. Exist
ing machine learning approaches often face challenges in integrating phenotype and genotype information and presenting to clinicians an interpretable model. We aim to provide informed patient stratification by introducing Hybrid Non-negative Matrix Factorization (HNMF) on phenotype and genotype matrices. HNMF simultaneously approximates the phenotypic and genetic matrices using different appropriate loss functions, and generates patient subtypes, phenotypic groups and genetic groups. Unlike previous methods, HNMF approximates phenotypic matrix under Frobenius loss, and genetic matrix under Kullback-Leibler (KL) loss. We propose an alternating projected gradient method to solve the approximation problem. Simulation shows HNMF converges fast and accurately to the true factor matrices. On real-world clinical dataset, we used the patient factor matrix as features to predict main cardiac mechanistic outcomes. We compared HNMF with six different models using phenotype or genotype features alone, with or without NMF, or using joint NMF with only one type of loss. HNMF significantly outperforms all comparison models. HNMF also reveals intuitive phenotype-genotype interactions that characterize cardiac abnormalities.
Motivation The genotype assignment problem consists of predicting, from the genotype of an individual, which of a known set of populations it originated from. The problem arises in a variety of contexts, including wildlife forensics, invasive species
detection and biodiversity monitoring. Existing approaches perform well under ideal conditions but are sensitive to a variety of common violations of the assumptions they rely on. Results In this article, we introduce Mycorrhiza, a machine learning approach for the genotype assignment problem. Our algorithm makes use of phylogenetic networks to engineer features that encode the evolutionary relationships among samples. Those features are then used as input to a Random Forests classifier. The classification accuracy was assessed on multiple published empirical SNP, microsatellite or consensus sequence datasets with wide ranges of size, geographical distribution and population structure and on simulated datasets. It compared favorably against widely used assessment tests or mixture analysis methods such as STRUCTURE and Admixture, and against another machine-learning based approach using principal component analysis for dimensionality reduction. Mycorrhiza yields particularly significant gains on datasets with a large average fixation index (FST) or deviation from the Hardy-Weinberg equilibrium. Moreover, the phylogenetic network approach estimates mixture proportions with good accuracy.
More advanced visualization tools are needed to assist with the analyses and interpretation of human metabolomics data, which are rapidly increasing in quantity and complexity. Using a dataset of several hundred bioactive lipid metabolites profiled i
n a cohort of over 1400 individuals sampled from a population-based community study, we performed a comprehensive set of association analyses relating all metabolites with eight demographic and cardiometabolic traits and outcomes. We then compared existing graphical approaches with an adapted rain plot approach to display the results of these analyses. The rain plot combines the features of a raindrop plot and a parallel heatmap approach to succinctly convey, in a single visualization, the results of relating complex metabolomics data with multiple phenotypes. This approach complements existing tools, particularly by facilitating comparisons between individual metabolites and across a range of pre-specified clinical outcomes. We anticipate that this single visualization technique may be further extended and applied to alternate study designs using different types of molecular phenotyping data.
Background: In the United States, 5.7 million patients are admitted annually to intensive care units (ICU), with costs exceeding $82 billion. Although close monitoring and dynamic assessment of patient acuity are key aspects of ICU care, both are lim
ited by the time constraints imposed on healthcare providers. Methods: Using the University of Florida Health (UFH) Integrated Data Repository as Honest Broker, we created a database with electronic health records data from a retrospective study cohort of 38,749 adult patients admitted to ICU at UF Health between 06/01/2014 and 08/22/2019. This repository includes demographic information, comorbidities, vital signs, laboratory values, medications with date and timestamps, and diagnoses and procedure codes for all index admission encounters as well as encounters within 12 months prior to index admission and 12 months follow-up. We developed algorithms to identify acuity status of the patient every four hours during each ICU stay. Results: We had 383,193 encounters (121,800 unique patients) admitted to the hospital, and 51,073 encounters (38,749 unique patients) with at least one ICU stay that lasted more than four hours. These patients requiring ICU admission had longer median hospital stay (7 days vs. 1 day) and higher in-hospital mortality (9.6% vs. 0.4%) compared with those not admitted to the ICU. Among patients who were admitted to the ICU and expired during hospital admission, more deaths occurred in the ICU than on general hospital wards (7.4% vs. 0.8%, respectively). Conclusions: We developed phenotyping algorithms that determined patient acuity status every four hours while admitted to the ICU. This approach may be useful in developing prognostic and clinical decision-support tools to aid patients, caregivers, and providers in shared decision-making processes regarding resource use and escalation of care.
In this review we summarize our recent efforts in trying to understand the role of heterogeneity in cancer progression by using neural networks to characterise different aspects of the mapping from a cancer cells genotype and environment to its pheno
type. Our central premise is that cancer is an evolving system subject to mutation and selection, and the primary conduit for these processes to occur is the cancer cell whose behaviour is regulated on multiple biological scales. The selection pressure is mainly driven by the microenvironment that the tumour is growing in and this acts directly upon the cell phenotype. In turn, the phenotype is driven by the intracellular pathways that are regulated by the genotype. Integrating all of these processes is a massive undertaking and requires bridging many biological scales (i.e. genotype, pathway, phenotype and environment) that we will only scratch the surface of in this review. We will focus on models that use neural networks as a means of connecting these different biological scales, since they allow us to easily create heterogeneity for selection to act upon and importantly this heterogeneity can be implemented at different biological scales. More specifically, we consider three different neural networks that bridge different aspects of these scales and the dialogue with the micro-environment, (i) the impact of the micro-environment on evolutionary dynamics, (ii) the mapping from genotype to phenotype under drug-induced perturbations and (iii) pathway activity in both normal and cancer cells under different micro-environmental conditions.
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