A phenome-guided drug repositioning through a latent variable model

Background

The phenome represents a distinct set of information in the human population. It has been explored particularly in its relationship with the genome to identify correlations for diseases. The phenome has been also explored for drug repositioning with efforts focusing on the search space for the most similar candidate drugs. For a comprehensive analysis of the phenome, we assumed that all phenotypes (indications and side effects) were inter-connected with a probabilistic distribution and this characteristic may offer an opportunity to identify new therapeutic indications for a given drug. Correspondingly, we employed Latent Dirichlet Allocation (LDA), which introduces latent variables (topics) to govern the phenome distribution.

Results

We developed our model on the phenome information in Side Effect Resource (SIDER). We first developed a LDA model optimized based on its recovery potential through perturbing the drug-phenotype matrix for each of the drug-indication pairs where each drug-indication relationship was switched to “unknown” one at the time and then recovered based on the remaining drug-phenotype pairs. Of the probabilistically significant pairs, 70% was successfully recovered. Next, we applied the model on the whole phenome to narrow down repositioning candidates and suggest alternative indications. We were able to retrieve approved indications of 6 drugs whose indications were not listed in SIDER. For 908 drugs that were present with their indication information, our model suggested alternative treatment options for further investigations. Several of the suggested new uses can be supported with information from the scientific literature.

Conclusions

The results demonstrated that the phenome can be further analyzed by a generative model, which can discover probabilistic associations between drugs and therapeutic uses. In this regard, LDA serves as an enrichment tool to explore new uses of existing drugs by narrowing down the search space.

Electronic supplementary material

The online version of this article (doi:10.1186/1471-2105-15-267) contains supplementary material, which is available to authorized users.     

Species Identification of Food Contaminating Beetles by Recognizing Patterns in Microscopic Images of Elytra Fragments

A crucial step of food contamination inspection is identifying the species of beetle fragments found in the sample, since the presence of some storage beetles is a good indicator of insanitation or potential food safety hazards. The current pratice, visual examination by human analysts, is time consuming and requires several years of experience. Here we developed a species identification algorithm which utilizes images of microscopic elytra fragments. The elytra, or hardened forewings, occupy a large portion of the body, and contain distinctive patterns. In addition, elytra fragments are more commonly recovered from processed food products than other body parts due to their hardness. As a preliminary effort, we chose 15 storage product beetle species frequently detected in food inspection. The elytra were then separated from the specimens and imaged under a microscope. Both global and local characteristics were quantified and used as feature inputs to artificial neural networks for species classification. With leave-one-out cross validation, we achieved overall accuracy of 80% through the proposed global and local features, which indicates that our proposed features could differentiate these species. Through examining the overall and per species accuracies, we further demonstrated that the local features are better suited than the global features for species identification. Future work will include robust testing with more beetle species and algorithm refinement for a higher accuracy.     

An Updated Review on Recent Advances in the Usage of Novel Therapeutic Peptides for Breast Cancer Treatment

International Journal of Peptide Research and Therapeutics - After the completion of the Human Genome Project, the strategic direction of modern genetics shifted towards functional genomics, which...