Biomedical Informatics Applications for Precision Management of Neurodegenerative Diseases

Modern medicine is in the midst of a revolution driven by “big data,” rapidly advancing computing power, and broader integration of technology into healthcare. Highly detailed and individualized profiles of both health and disease states are now possible, including biomarkers, genomic profiles, cognitive and behavioral phenotypes, high-frequency assessments, and medical imaging. Although these data are incredibly complex, they can potentially be used to understand multi-determinant causal relationships, elucidate modifiable factors, and ultimately customize treatments based on individual parameters. Especially for neurodegenerative diseases, where an effective therapeutic agent has yet to be discovered, there remains a critical need for an interdisciplinary perspective on data and information management due to the number of unanswered questions. Biomedical informatics is a multidisciplinary field that falls at the intersection of information technology, computer and data science, engineering, and healthcare that will be instrumental for uncovering novel insights into neurodegenerative disease research, including both causal relationships and therapeutic targets and maximizing the utility of both clinical and research data. The present study aims to provide a brief overview of biomedical informatics and how clinical data applications such as clinical decision support tools can be developed to derive new knowledge from the wealth of available data to advance clinical care and scientific research of neurodegenerative diseases in the era of precision medicine

Multi-agent evolutionary systems for the generation of complex virtual worlds

Modern films, games and virtual reality applications are dependent on convincing computer graphics. Highly complex models are a requirement for the successful delivery of many scenes and environments. While workflows such as rendering, compositing and animation have been streamlined to accommodate increasing demands, modelling complex models is still a laborious task. This paper introduces the computational benefits of an Interactive Genetic Algorithm (IGA) to computer graphics modelling while compensating the effects of user fatigue, a common issue with Interactive Evolutionary Computation. An intelligent agent is used in conjunction with an IGA that offers the potential to reduce the effects of user fatigue by learning from the choices made by the human designer and directing the search accordingly. This workflow accelerates the layout and distribution of basic elements to form complex models. It captures the designer's intent through interaction, and encourages playful discovery

On the Road to Accurate Biomarkers for Cardiometabolic Diseases by Integrating Precision and Gender Medicine Approaches

The need to facilitate the complex management of cardiometabolic diseases (CMD) has led to the detection of many biomarkers, however, there are no clear explanations of their role in the prevention, diagnosis or prognosis of these diseases. Molecules associated with disease pathways represent valid disease surrogates and well-fitted CMD biomarkers. To address this challenge, data from multi-omics types (genomics, epigenomics, transcriptomics, proteomics, metabolomics, microbiomics, and nutrigenomics), from human and animal models, have become available. However, individual omics types only provide data on a small part of molecules involved in the complex CMD mechanisms, whereas, here, we propose that their integration leads to multidimensional data. Such data provide a better understanding of molecules related to CMD mechanisms and, consequently, increase the possibility of identifying well-fitted biomarkers. In addition, the application of gender medicine also helps to identify accurate biomarkers according to gender, facilitating a differential CMD management. Accordingly, the impact of gender differences in CMD pathophysiology has been widely demonstrated, where gender is referred to the complex interrelation and integration of sex (as a biological and functional marker of the human body) and psychological and cultural behavior (due to ethnical, social, and religious background). In this review, all these aspects are described and discussed, as well as potential limitations and future directions in this incipient field

PASS: a simple classifier system for data analysis

Let x be a vector of predictors and y a scalar response associated with it. Consider the regression problem of inferring the relantionship between predictors and response on the basis of a sample of observed pairs (x,y). This is a familiar problem for which a variety of methods are available. This paper describes a new method based on the classifier system approach to problem solving. Classifier systems provide a rich framework for learning and induction, and they have been suc:cessfully applied in the artificial intelligence literature for some time. The present method emiches the simplest classifier system architecture with some new heuristic and explores its potential in a purely inferential context. A prototype called PASS (Predictive Adaptative Sequential System) has been built to test these ideas empirically. Preliminary Monte Carlo experiments indicate that PASS is able to discover the structure imposed on the data in a wide array of cases

Structural Prediction of Protein–Protein Interactions by Docking: Application to Biomedical Problems

A huge amount of genetic information is available thanks to the recent advances in sequencing technologies and the larger computational capabilities, but the interpretation of such genetic data at phenotypic level remains elusive. One of the reasons is that proteins are not acting alone, but are specifically interacting with other proteins and biomolecules, forming intricate interaction networks that are essential for the majority of cell processes and pathological conditions. Thus, characterizing such interaction networks is an important step in understanding how information flows from gene to phenotype. Indeed, structural characterization of protein–protein interactions at atomic resolution has many applications in biomedicine, from diagnosis and vaccine design, to drug discovery. However, despite the advances of experimental structural determination, the number of interactions for which there is available structural data is still very small. In this context, a complementary approach is computational modeling of protein interactions by docking, which is usually composed of two major phases: (i) sampling of the possible binding modes between the interacting molecules and (ii) scoring for the identification of the correct orientations. In addition, prediction of interface and hot-spot residues is very useful in order to guide and interpret mutagenesis experiments, as well as to understand functional and mechanistic aspects of the interaction. Computational docking is already being applied to specific biomedical problems within the context of personalized medicine, for instance, helping to interpret pathological mutations involved in protein–protein interactions, or providing modeled structural data for drug discovery targeting protein–protein interactions.Spanish Ministry of Economy grant number BIO2016-79960-R; D.B.B. is supported by a predoctoral fellowship from CONACyT; M.R. is supported by an FPI fellowship from the Severo Ochoa program. We are grateful to the Joint BSC-CRG-IRB Programme in Computational Biology.Peer ReviewedPostprint (author's final draft

Using rule extraction to improve the comprehensibility of predictive models.

Whereas newer machine learning techniques, like artifficial neural net-works and support vector machines, have shown superior performance in various benchmarking studies, the application of these techniques remains largely restricted to research environments. A more widespread adoption of these techniques is foiled by their lack of explanation capability which is required in some application areas, like medical diagnosis or credit scoring. To overcome this restriction, various algorithms have been proposed to extract a meaningful description of the underlying `blackbox' models. These algorithms' dual goal is to mimic the behavior of the black box as closely as possible while at the same time they have to ensure that the extracted description is maximally comprehensible. In this research report, we first develop a formal definition of`rule extraction and comment on the inherent trade-off between accuracy and comprehensibility. Afterwards, we develop a taxonomy by which rule extraction algorithms can be classiffied and discuss some criteria by which these algorithms can be evaluated. Finally, an in-depth review of the most important algorithms is given.This report is concluded by pointing out some general shortcomings of existing techniques and opportunities for future research.Models; Model; Algorithms; Criteria; Opportunities; Research; Learning; Neural networks; Networks; Performance; Benchmarking; Studies; Area; Credit; Credit scoring; Behavior; Time;

Mathematics Is Biology's Next Microscope, Only Better; Biology Is Mathematics' Next Physics, Only Better

Joel Cohen offers a historical and prospective analysis of the relationship between mathematics and biolog