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Biology subjects

Poleksic, A.

Publications and source records attributed to Poleksic, A..

3 recordsLinked to original sources

Hyperbolic matrix factorization hints at the native space of biological systems

Past research in systems biology has taken for granted the Euclidean geometry of biological space. This has not only drawn parallels to other fields but has also been convenient due to the ample statistical and numerical optimization tools available to address the core task and downstream machine learning problems. However, emerging theoretical studies now demonstrate that biological databases exhibit hierarchical topology, characterized by heterogeneous degree distribution and a high degree of clustering, thus contradicting the flat geometry assumption. Namely, since the number of nodes in hierarchical structures grows exponentially with node depth, the biological networks naturally reside in a hyperbolic space where the circle circumference and disk area are the exponential functions of the radius. To test these claims and assess potential benefits of the applications grounded in the above hypothesis, we have developed a mathematical framework and an accompanying computational procedure for matrix factorization and implied biological relationship inference in hyperbolic space. Not only does our study demonstrate a significant increase in the accuracy of hyperbolic embedding compared to Euclidean embedding, but it also shows that the latent dimension of an optimal hyperbolic embedding is by more than an order of magnitude smaller than the latent dimension of an optimal Euclidean embedding. We see this as additional evidence that hyperbolic geometry, rather than Euclidean, underlines the biological system.

systems biology↗

Overcoming sparseness of biomedical networks to identify drug repositioning candidates

Modeling complex biological systems is necessary to understand biochemical interactions behind pharmacological effects of drugs. Successful in silico drug repurposing requires a thorough exploration of diverse biochemical concepts and their relationships, including drugs adverse reactions, drug targets, disease symptoms, as well as disease associated genes and their pathways, to name a few. We present a computational method for inferring drug-disease associations from complex but incomplete and biased biological networks. Our method employs the compressed sensing technique to overcome the sparseness of biomedical data and, in turn, to enrich the set of verified relationships between different biomedical entities. We present a strategy for identifying network paths supportive of drug efficacy as well as a computational procedure capable of combining different network patterns to better distinguish treatments from non-treatments. The data and programs are freely available at http://bioinfo.cs.uni.edu/AEONET.html.

systems biology↗

Predicting serious rare adverse reactions of novel chemicals

Adverse drug reactions (ADRs) are one of the main causes of death and a major financial burden on the worlds economy. Due to the limitations of the animal model, computational prediction of serious, rare ADRs is invaluable. However, current state-of-the-art computational methods do not yield significantly better predictions of rare ADRs than random guessing. We present a novel method, based on the theory of \"compressed sensing\", which can accurately predict serious side-effects of candidate and market drugs. Not only is our method able to infer new chemical-ADR associations using existing noisy, biased, and incomplete databases, but our data also demonstrates that the accuracy of our approach in predicting a serious adverse reaction (ADR) for a candidate drug increases with increasing knowledge of other ADRs associated with the drug. In practice, this means that as the candidate drug moves up the different stages of clinical trials, the prediction accuracy of our method will increase accordingly. Thus, the compressed sensing based computational method reported here represents a major advance in predicting severe rare ADRs, and may facilitate reducing the time and cost of drug discovery and development.

pharmacology and toxicology↗