Predicting drug-target interaction network using deep learning model.

BACKGROUND: Traditional methods for drug discovery are time-consuming and expensive, so efforts are being made to repurpose existing drugs. To find new ways for drug repurposing, many computational approaches have been proposed to predict drug-target interactions (DTIs). However, due to the high-dimensional nature of the data sets extracted from drugs and targets, traditional machine learning approaches, such as logistic regression analysis, cannot analyze these data sets efficiently. To overcome this issue, we propose LASSO (Least absolute shrinkage and selection operator)-based regularized linear classification models and a LASSO-DNN (Deep Neural Network) model based on LASSO feature selection to predict DTIs. These methods are demonstrated for repurposing drugs for breast cancer treatment. METHODS: We collected drug descriptors, protein sequence data from Drugbank and protein domain information from NCBI. Validated DTIs were downloaded from Drugbank. A new similarity-based approach was developed to build the negative DTIs. We proposed multiple LASSO models to integrate different combinations of feature sets to explore the prediction power and predict DTIs. Furthermore, building on the features extracted from the LASSO models with the best performance, we also introduced a LASSO-DNN model to predict DTIs. The performance of our newly proposed DNN model (LASSO-DNN) was compared with the LASSO, standard logistic (SLG) regression, support vector machine (SVM), and standard DNN models. RESULTS: Experimental results showed that the LASSO-DNN over performed the SLG, LASSO, SVM and standard DNN models. In particular, the LASSO models with protein tripeptide composition (TC) features and domain features were superior to those that contained other protein information, which may imply that TC and domain information could be better representations of proteins. Furthermore, we showed that the top ranked DTIs predicted using the LASSO-DNN model can potentially be used for repurposing existing drugs for breast cancer based on risk gene information. CONCLUSIONS: In summary, we demonstrated that the efficient representations of drug and target features are key for building learning models for predicting DTIs. The disease-associated risk genes identified from large-scale genomic studies are the potential drug targets, which can be used for drug repurposing.

Data Preparation for West Nile Virus Agent-Based Modelling: Protocol for Processing Bird Population Estimates and Incorporating ArcMap in AnyLogic.

BACKGROUND: West Nile Virus (WNV) was first isolated in 1937. Since the 1950s, many outbreaks have occurred in various countries. The first appearance of infected birds in Manitoba, Canada was in 2002. OBJECTIVE: This paper describes the data preparation phase of setting up a geographic information system (GIS) simulation environment for WNV Agent-Based Modelling in Manitoba. METHODS: The main technology used in this protocol is based on AnyLogic and ArcGIS software. A diverse variety of topics and techniques regarding the data collection phase are presented, as modelling WNV has many disparate attributes, including landscape and weather impacts on mosquito population dynamics and birds' roosting locations, population count, and movement patterns. RESULTS: Different maps were combined to create a grid land cover map of Manitoba, Canada in a shapefile format compatible with AnyLogic, in order to modulate mosquito parameters. A significant amount of data regarding 152 bird species, along with their population estimates and locations in Manitoba, were gathered and assembled. Municipality shapefile maps were converted to built-in AnyLogic GIS regions for better compatibility with census data and initial placement of human agents. Accessing shapefiles and their databases in AnyLogic are also discussed. CONCLUSIONS: AnyLogic simulation software in combination with Esri ArcGIS provides a powerful toolbox for developers and modellers to simulate almost any GIS-based environment or process. This research should be useful to others working on a variety of mosquito-borne diseases (eg, Zika, dengue, and chikungunya) by demonstrating the importance of data relating to Manitoba and/or introducing procedures to compile such data.

A mHealth application for chronic wound care: findings of a user trial.

This paper reports on the findings of a user trial of a mHealth application for pressure ulcer (bedsore) documentation. Pressure ulcers are a leading iatrogenic cause of death in developed countries and significantly impact quality of life for those affected. Pressure ulcers will be an increasing public health concern as the population ages. Electronic information systems are being explored to improve consistency and accuracy of documentation, improve patient and caregiver experience and ultimately improve patient outcomes. A software application was developed for Android Smartphones and tablets and was trialed in a personal care home in Western Canada. The software application provides an electronic medical record for chronic wounds, replacing nurses' paper-based charting and is positioned for integration with facility's larger eHealth framework. The mHealth application offers three intended benefits over paper-based charting of chronic wounds, including: (1) the capacity for remote consultation (telehealth between facilities, practitioners, and/or remote communities), (2) data organization and analysis, including built-in alerts, automatically-generated text-based and graph-based wound histories including wound images, and (3) tutorial support for non-specialized caregivers. The user trial yielded insights regarding the software application's design and functionality in the clinical setting, and highlighted the key role of wound photographs in enhancing patient and caregiver experiences, enhancing communication between multiple healthcare professionals, and leveraging the software's telehealth capacities.

An agent based model for simulating the spread of sexually transmitted infections.

This work uses agent-based modelling (ABM) to simulate sexually transmitted infection (STIs) spread within a population of 1000 agents over a 10-year period, as a preliminary investigation of the suitability of ABM methodology to simulate STI spread. The work contrasts compartmentalized mathematical models that fail to account for individual agents, and ABMs commonly applied to simulate the spread of respiratory infections. The model was developed in C++ using the Boost 1.47.0 libraries for the normal distribution and OpenGL for visualization. Sixteen agent parameters interact individually and in combination to govern agent profiles and behaviours relative to infection probabilities. The simulation results provide qualitative comparisons of STI mitigation strategies, including the impact of condom use, promiscuity, the form of the friend network, and mandatory STI testing. Individual and population-wide impacts were explored, with individual risk being impacted much more dramatically by population-level behaviour changes as compared to individual behaviour changes.

Agent-based modeling of the spread of influenza-like illness in an emergency department: a simulation study.

The objective of this paper was to develop an agent-based modeling framework in order to simulate the spread of influenza virus infection on a layout based on a representative hospital emergency department in Winnipeg, Canada. In doing so, the study complements mathematical modeling techniques for disease spread, as well as modeling applications focused on the spread of antibiotic-resistant nosocomial infections in hospitals. Twenty different emergency department scenarios were simulated, with further simulation of four infection control strategies. The agent-based modeling approach represents systems modeling, in which the emergency department was modeled as a collection of agents (patients and healthcare workers) and their individual characteristics, behaviors, and interactions. The framework was coded in C++ using Qt4 libraries running under the Linux operating system. A simple ordinary least squares (OLS) regression was used to analyze the data, in which the percentage of patients that became infected in one day within the simulation was the dependent variable. The results suggest that within the given instance context, patient-oriented infection control policies (alternate treatment streams, masking symptomatic patients) tend to have a larger effect than policies that target healthcare workers. The agent-based modeling framework is a flexible tool that can be made to reflect any given environment; it is also a decision support tool for practitioners and policymakers to assess the relative impact of infection control strategies. The framework illuminates scenarios worthy of further investigation, as well as counterintuitive findings.

Improving Agent Based Models and Validation through Data Fusion.

This work is contextualized in research in modeling and simulation of infection spread within a community or population, with the objective to provide a public health and policy tool in assessing the dynamics of infection spread and the qualitative impacts of public health interventions. This work uses the integration of real data sources into an Agent Based Model (ABM) to simulate respiratory infection spread within a small municipality. Novelty is derived in that the data sources are not necessarily obvious within ABM infection spread models. The ABM is a spatial-temporal model inclusive of behavioral and interaction patterns between individual agents on a real topography. The agent behaviours (movements and interactions) are fed by census / demographic data, integrated with real data from a telecommunication service provider (cellular records) and person-person contact data obtained via a custom 3G Smartphone application that logs Bluetooth connectivity between devices. Each source provides data of varying type and granularity, thereby enhancing the robustness of the model. The work demonstrates opportunities in data mining and fusion that can be used by policy and decision makers. The data become real-world inputs into individual SIR disease spread models and variants, thereby building credible and non-intrusive models to qualitatively simulate and assess public health interventions at the population level.

Agent based modeling of "crowdinforming" as a means of load balancing at emergency departments.

This work extends ongoing development of a framework for modeling the spread of contact-transmission infectious diseases. The framework is built upon Agent Based Modeling (ABM), with emphasis on urban scale modelling integrated with institutional models of hospital emergency departments. The method presented here includes ABM modeling an outbreak of influenza-like illness (ILI) with concomitant surges at hospital emergency departments, and illustrates the preliminary modeling of 'crowdinforming' as an intervention. 'Crowdinforming', a component of 'crowdsourcing', is characterized as the dissemination of collected and processed information back to the 'crowd' via public access. The objective of the simulation is to allow for effective policy evaluation to better inform the public of expected wait times as part of their decision making process in attending an emergency department or clinic. In effect, this is a means of providing additional decision support garnered from a simulation, prior to real world implementation. The conjecture is that more optimal service delivery can be achieved under balanced patient loads, compared to situations where some emergency departments are overextended while others are underutilized. Load balancing optimization is a common notion in many operations, and the simulation illustrates that 'crowdinforming' is a potential tool when used as a process control parameter to balance the load at emergency departments as well as serving as an effective means to direct patients during an ILI outbreak with temporary clinics deployed. The information provided in the 'crowdinforming' model is readily available in a local context, although it requires thoughtful consideration in its interpretation. The extension to a wider dissemination of information via a web service is readily achievable and presents no technical obstacles, although political obstacles may be present. The 'crowdinforming' simulation is not limited to arrivals of patients at emergency departments due to ILI; it applies equally to any scenarios where patients arrive in any arrival pattern that may cause disparity in the waiting times at multiple facilities.

Epidemic modeling with discrete-space scheduled walkers: extensions and research opportunities.

BACKGROUND: This exploratory paper outlines an epidemic simulator built on an agent-based, data-driven model of the spread of a disease within an urban environment. An intent of the model is to provide insight into how a disease may reach a tipping point, spreading to an epidemic of uncontrollable proportions. METHODS: As a complement to analytical methods, simulation is arguably an effective means of gaining a better understanding of system-level disease dynamics within a population and offers greater utility in its modeling capabilities. Our investigation is based on this conjecture, supported by data-driven models that are reasonable, realistic and practical, in an attempt to demonstrate their efficacy in studying system-wide epidemic phenomena. An agent-based model (ABM) offers considerable flexibility in extending the study of the phenomena before, during and after an outbreak or catastrophe. RESULTS: An agent-based model was developed based on a paradigm of a 'discrete-space scheduled walker' (DSSW), modeling a medium-sized North American City of 650,000 discrete agents, built upon a conceptual framework of statistical reasoning (law of large numbers, statistical mechanics) as well as a correct-by-construction bias. The model addresses where, who, when and what elements, corresponding to network topography and agent characteristics, behaviours, and interactions upon that topography. The DSSW-ABM has an interface and associated scripts that allow for a variety of what-if scenarios modeling disease spread throughout the population, and for data to be collected and displayed via a web browser. CONCLUSION: This exploratory paper also presents several research opportunities for exploiting data sources of a non-obvious and disparate nature for the purposes of epidemic modeling. There is an increasing amount and variety of data that will continue to contribute to the accuracy of agent-based models and improve their utility in modeling disease spread. The model developed here is well suited to diseases where there is not a predisposition for contraction within the population. One of the advantages of agent-based modeling is the ability to set up a rare event and develop policy as to how one may mitigate damages arising from it.

Models of emergency departments for reducing patient waiting times.

In this paper, we apply both agent-based models and queuing models to investigate patient access and patient flow through emergency departments. The objective of this work is to gain insights into the comparative contributions and limitations of these complementary techniques, in their ability to contribute empirical input into healthcare policy and practice guidelines. The models were developed independently, with a view to compare their suitability to emergency department simulation. The current models implement relatively simple general scenarios, and rely on a combination of simulated and real data to simulate patient flow in a single emergency department or in multiple interacting emergency departments. In addition, several concepts from telecommunications engineering are translated into this modeling context. The framework of multiple-priority queue systems and the genetic programming paradigm of evolutionary machine learning are applied as a means of forecasting patient wait times and as a means of evolving healthcare policy, respectively. The models' utility lies in their ability to provide qualitative insights into the relative sensitivities and impacts of model input parameters, to illuminate scenarios worthy of more complex investigation, and to iteratively validate the models as they continue to be refined and extended. The paper discusses future efforts to refine, extend, and validate the models with more data and real data relative to physical (spatial-topographical) and social inputs (staffing, patient care models, etc.). Real data obtained through proximity location and tracking system technologies is one example discussed.