1,722 research outputs found
Rotationally-invariant mapping of scalar and orientational metrics of neuronal microstructure with diffusion MRI
We develop a general analytical and numerical framework for estimating intra-
and extra-neurite water fractions and diffusion coefficients, as well as
neurite orientational dispersion, in each imaging voxel. By employing a set of
rotational invariants and their expansion in the powers of diffusion weighting,
we analytically uncover the nontrivial topology of the parameter estimation
landscape, showing that multiple branches of parameters describe the
measurement almost equally well, with only one of them corresponding to the
biophysical reality. A comprehensive acquisition shows that the branch choice
varies across the brain. Our framework reveals hidden degeneracies in MRI
parameter estimation for neuronal tissue, provides microstructural and
orientational maps in the whole brain without constraints or priors, and
connects modern biophysical modeling with clinical MRI.Comment: 25 pages, 12 figures, elsarticle two-colum
Relation Prediction over Biomedical Knowledge Bases for Drug Repositioning
Identifying new potential treatment options for medical conditions that cause human disease burden is a central task of biomedical research. Since all candidate drugs cannot be tested with animal and clinical trials, in vitro approaches are first attempted to identify promising candidates. Likewise, identifying other essential relations (e.g., causation, prevention) between biomedical entities is also critical to understand biomedical processes. Hence, it is crucial to develop automated relation prediction systems that can yield plausible biomedical relations to expedite the discovery process. In this dissertation, we demonstrate three approaches to predict treatment relations between biomedical entities for the drug repositioning task using existing biomedical knowledge bases. Our approaches can be broadly labeled as link prediction or knowledge base completion in computer science literature. Specifically, first we investigate the predictive power of graph paths connecting entities in the publicly available biomedical knowledge base, SemMedDB (the entities and relations constitute a large knowledge graph as a whole). To that end, we build logistic regression models utilizing semantic graph pattern features extracted from the SemMedDB to predict treatment and causative relations in Unified Medical Language System (UMLS) Metathesaurus. Second, we study matrix and tensor factorization algorithms for predicting drug repositioning pairs in repoDB, a general purpose gold standard database of approved and failed drug–disease indications. The idea here is to predict repoDB pairs by approximating the given input matrix/tensor structure where the value of a cell represents the existence of a relation coming from SemMedDB and UMLS knowledge bases. The essential goal is to predict the test pairs that have a blank cell in the input matrix/tensor based on the shared biomedical context among existing non-blank cells. Our final approach involves graph convolutional neural networks where entities and relation types are embedded in a vector space involving neighborhood information. Basically, we minimize an objective function to guide our model to concept/relation embeddings such that distance scores for positive relation pairs are lower than those for the negative ones. Overall, our results demonstrate that recent link prediction methods applied to automatically curated, and hence imprecise, knowledge bases can nevertheless result in high accuracy drug candidate prediction with appropriate configuration of both the methods and datasets used
HeTriNet: Heterogeneous Graph Triplet Attention Network for Drug-Target-Disease Interaction
Modeling the interactions between drugs, targets, and diseases is paramount
in drug discovery and has significant implications for precision medicine and
personalized treatments. Current approaches frequently consider drug-target or
drug-disease interactions individually, ignoring the interdependencies among
all three entities. Within human metabolic systems, drugs interact with protein
targets in cells, influencing target activities and subsequently impacting
biological pathways to promote healthy functions and treat diseases. Moving
beyond binary relationships and exploring tighter triple relationships is
essential to understanding drugs' mechanism of action (MoAs). Moreover,
identifying the heterogeneity of drugs, targets, and diseases, along with their
distinct characteristics, is critical to model these complex interactions
appropriately. To address these challenges, we effectively model the
interconnectedness of all entities in a heterogeneous graph and develop a novel
Heterogeneous Graph Triplet Attention Network (\texttt{HeTriNet}).
\texttt{HeTriNet} introduces a novel triplet attention mechanism within this
heterogeneous graph structure. Beyond pairwise attention as the importance of
an entity for the other one, we define triplet attention to model the
importance of pairs for entities in the drug-target-disease triplet prediction
problem. Experimental results on real-world datasets show that
\texttt{HeTriNet} outperforms several baselines, demonstrating its remarkable
proficiency in uncovering novel drug-target-disease relationships.Comment: 13 pages, 3 figures, 6 table
Matrix Factorization at Scale: a Comparison of Scientific Data Analytics in Spark and C+MPI Using Three Case Studies
We explore the trade-offs of performing linear algebra using Apache Spark,
compared to traditional C and MPI implementations on HPC platforms. Spark is
designed for data analytics on cluster computing platforms with access to local
disks and is optimized for data-parallel tasks. We examine three widely-used
and important matrix factorizations: NMF (for physical plausability), PCA (for
its ubiquity) and CX (for data interpretability). We apply these methods to
TB-sized problems in particle physics, climate modeling and bioimaging. The
data matrices are tall-and-skinny which enable the algorithms to map
conveniently into Spark's data-parallel model. We perform scaling experiments
on up to 1600 Cray XC40 nodes, describe the sources of slowdowns, and provide
tuning guidance to obtain high performance
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