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Purpose: To evaluate the value of convolutional neural network (CNN) in the diagnosis of human brain tumor or Alzheimer's disease by MR spectroscopic imaging (MRSI) and to compare its Matthews correlation coefficient (MCC) score against that of other machine learning methods and previous evaluation of the same data. We address two challenges: 1) limited number of cases in MRSI datasets and 2) interpretability of results in the form of relevant spectral regions. Methods: A shallow CNN with only one hidden layer and an ad-hoc loss function was constructed involving two branches for processing spectral and image features of a brain voxel respectively. Each branch consists of a single convolutional hidden layer. The output of the two convolutional layers is merged and fed to a classification layer that outputs class predictions for the given brain voxel. Results: Our CNN method separated glioma grades 3 and 4 and identified Alzheimer's disease patients using MRSI and complementary MRI data with high MCC score (Area Under the Curve were 0.87 and 0.91 respectively). The results demonstrated superior effectiveness over other popular methods as Partial Least Squares or Support Vector Machines. Also, our method automatically identified the spectral regions most important in the diagnosis process and we show that these are in good agreement with existing biomarkers from the literature. Conclusion: Shallow CNNs models integrating image and spectral features improved quantitative and exploration and diagnosis of brain diseases for research and clinical purposes. Software is available at https://bitbucket.org/TeslaH2O/cnn_mrsi. [ABSTRACT FROM AUTHOR]

High quality radiology reporting of chest X-ray images is of core importance for high-quality patient diagnosis and care. Automatically generated reports can assist radiologists by reducing their workload and even may prevent errors. Machine Learning (ML) models for this task take an X-ray image as input and output a sequence of words. In this work, we show that ML models for this task based on the popular encoder-decoder approach, like 'Show, Attend and Tell' (SA&T) have similar or worse performance than models that do not use the input image, called unconditioned baseline. An unconditioned model achieved diagnostic accuracy of 0.91 on the IU chest X-ray dataset, and significantly outperformed SA&T (0.877) and other popular ML models (p-value < 0.001). This unconditioned model also outperformed SA&T and similar ML methods on the BLEU-4 and METEOR metrics. Also, an unconditioned version of SA&T obtained by permuting the reports generated from images of the test set, achieved diagnostic accuracy of 0.862, comparable to that of SA&T (p-value ≥ 0.05). [ABSTRACT FROM AUTHOR]

Motivation: Genome-scale metabolic networks can be modeled in a constraint-based fashion. Reaction stoichiometry combined with flux capacity constraints determine the space of allowable reaction rates. This space is often large and a central challenge in metabolic modeling is finding the biologically most relevant flux distributions. A widely used method is flux balance analysis (FBA), which optimizes a biologically relevant objective such as growth or ATP production. Although FBA has proven to be highly useful for predicting growth and byproduct secretion, it cannot predict the intracellular fluxes under all environmental conditions. Therefore, alternative strategies have been developed to select flux distributions that are in agreement with experimental “omics” data, or by incorporating experimental flux measurements. The latter, unfortunately can only be applied to a limited set of reactions and is currently not feasible at the genome-scale. On the other hand, it has been observed that micro-organisms favor a suboptimal growth rate, possibly in exchange for a more “flexible” metabolic network. Instead of dedicating the internal network state to an optimal growth rate in one condition, a suboptimal growth rate is used, that allows for an easier switch to other nutrient sources. A small decrease in growth rate is exchanged for a relatively large gain in metabolic capability to adapt to changing environmental conditions. Results: Here, we propose Maximum Metabolic Flexibility (MMF) a computational method that utilizes this observation to find the most probable intracellular flux distributions. By mapping measured flux data from central metabolism to the genome-scale models of Escherichia coli and Saccharomyces cerevisiae we show that i) indeed, most of the measured fluxes agree with a high adaptability of the network, ii) this result can be used to further reduce the space of feasible solutions iii) this reduced space improves the quantitative predictions made by FBA and contains a significantly larger fraction of the measured fluxes compared to the flux space that was reduced by a uniform sampling approach and iv) MMF can be used to select reactions in the network that contribute most to the steady-state flux space. Constraining the selected reactions improves the quantitative predictions of FBA considerably more than adding an equal amount of flux constraints, selected using a more naïve approach. Our method can be applied to any cell type without requiring prior information. Availability: MMF is freely available as a MATLAB plugin at: . [ABSTRACT FROM AUTHOR]

Constraint-based models of metabolic networks are typically underdetermined, because they contain more reactions than metabolites. Therefore the solutions to this system do not consist of unique flux rates for each reaction, but rather a space of possible flux rates. By uniformly sampling this space, an estimated probability distribution for each reaction’s flux in the network can be obtained. However, sampling a high dimensional network is time-consuming. Furthermore, the constraints imposed on the network give rise to an irregularly shaped solution space. Therefore more tailored, efficient sampling methods are needed. We propose an efficient sampling algorithm (called optGpSampler), which implements the Artificial Centering Hit-and-Run algorithm in a different manner than the sampling algorithm implemented in the COBRA Toolbox for metabolic network analysis, here called gpSampler. Results of extensive experiments on different genome-scale metabolic networks show that optGpSampler is up to 40 times faster than gpSampler. Application of existing convergence diagnostics on small network reconstructions indicate that optGpSampler converges roughly ten times faster than gpSampler towards similar sampling distributions. For networks of higher dimension (i.e. containing more than 500 reactions), we observed significantly better convergence of optGpSampler and a large deviation between the samples generated by the two algorithms. Availability:optGpSampler for Matlab and Python is available for non-commercial use at: http://cs.ru.nl/~wmegchel/optGpSampler/. [ABSTRACT FROM AUTHOR]

In silico discovery of interactions between drug compounds and target proteins is of core importance for improving the efficiency of the laborious and costly experimental determination of drug-target interaction. Drug-target interaction data are available for many classes of pharmaceutically useful target proteins including enzymes, ion channels, GPCRs and nuclear receptors. However, current drug-target interaction databases contain a small number of drug-target pairs which are experimentally validated interactions. In particular, for some drug compounds (or targets) there is no available interaction. This motivates the need for developing methods that predict interacting pairs with high accuracy also for these 'new' drug compounds (or targets). We show that a simple weighted nearest neighbor procedure is highly effective for this task. We integrate this procedure into a recent machine learning method for drug-target interaction we developed in previous work. Results of experiments indicate that the resulting method predicts true interactions with high accuracy also for new drug compounds and achieves results comparable or better than those of recent state-of-the-art algorithms. Software is publicly available at http://cs.ru.nl/~tvanlaarhoven/drugtarget2013/. [ABSTRACT FROM AUTHOR]

Unlabelled: Constraint-based models of metabolic networks are typically underdetermined, because they contain more reactions than metabolites. Therefore the solutions to this system do not consist of unique flux rates for each reaction, but rather a space of possible flux rates. By uniformly sampling this space, an estimated probability distribution for each reaction's flux in the network can be obtained. However, sampling a high dimensional network is time-consuming. Furthermore, the constraints imposed on the network give rise to an irregularly shaped solution space. Therefore more tailored, efficient sampling methods are needed. We propose an efficient sampling algorithm (called optGpSampler), which implements the Artificial Centering Hit-and-Run algorithm in a different manner than the sampling algorithm implemented in the COBRA Toolbox for metabolic network analysis, here called gpSampler. Results of extensive experiments on different genome-scale metabolic networks show that optGpSampler is up to 40 times faster than gpSampler. Application of existing convergence diagnostics on small network reconstructions indicate that optGpSampler converges roughly ten times faster than gpSampler towards similar sampling distributions. For networks of higher dimension (i.e. containing more than 500 reactions), we observed significantly better convergence of optGpSampler and a large deviation between the samples generated by the two algorithms., Availability: optGpSampler for Matlab and Python is available for non-commercial use at: http://cs.ru.nl/~wmegchel/optGpSampler/.