Predictive models for anti-tubercular molecules using machine learning on high-throughput biological screening datasets

<p>Abstract</p> <p>Background</p> <p>Tuberculosis is a contagious disease caused by <it>Mycobacterium tuberculosis </it>(Mtb), affecting more than two billion people around the globe and is one of the major causes of morbidity and mortality in the developing world. Recent reports suggest that Mtb has been developing resistance to the widely used anti-tubercular drugs resulting in the emergence and spread of multi drug-resistant (MDR) and extensively drug-resistant (XDR) strains throughout the world. In view of this global epidemic, there is an urgent need to facilitate fast and efficient lead identification methodologies. Target based screening of large compound libraries has been widely used as a fast and efficient approach for lead identification, but is restricted by the knowledge about the target structure. Whole organism screens on the other hand are target-agnostic and have been now widely employed as an alternative for lead identification but they are limited by the time and cost involved in running the screens for large compound libraries. This could be possibly be circumvented by using computational approaches to prioritize molecules for screening programmes.</p> <p>Results</p> <p>We utilized physicochemical properties of compounds to train four supervised classifiers (Naïve Bayes, Random Forest, J48 and SMO) on three publicly available bioassay screens of Mtb inhibitors and validated the robustness of the predictive models using various statistical measures.</p> <p>Conclusions</p> <p>This study is a comprehensive analysis of high-throughput bioassay data for anti-tubercular activity and the application of machine learning approaches to create target-agnostic predictive models for anti-tubercular agents.</p

Therapeutic opportunities within the DNA damage response

The DNA damage response (DDR) is essential for maintaining the genomic integrity of the cell, and its disruption is one of the hallmarks of cancer. Classically, defects in the DDR have been exploited therapeutically in the treatment of cancer with radiation therapies or genotoxic chemotherapies. More recently, protein components of the DDR systems have been identified as promising avenues for targeted cancer therapeutics. Here, we present an in-depth analysis of the function, role in cancer and therapeutic potential of 450 expert-curated human DDR genes. We discuss the DDR drugs that have been approved by the US Food and Drug Administration (FDA) or that are under clinical investigation. We examine large-scale genomic and expression data for 15 cancers to identify deregulated components of the DDR, and we apply systematic computational analysis to identify DDR proteins that are amenable to modulation by small molecules, highlighting potential novel therapeutic targets

An Empirical Comparison of Consumer Innovation Adoption Models: Implications for Subsistence Marketplaces

So called “pro-poor” innovations may improve consumer wellbeing in subsistence marketplaces. However, there is little research that integrates the area with the vast literature on innovation adoption. Using a questionnaire where respondents were asked to provide their evaluations about a mobile banking innovation, this research fills this gap by providing empirical evidence of the applicability of existing innovation adoption models in subsistence marketplaces. The study was conducted in Bangladesh among a geographically dispersed sample. The data collected allowed an empirical comparison of models in a subsistence context. The research reveals the most useful models in this context to be the Value Based Adoption Model and the Consumer Acceptance of Technology model. In light of these findings and further examination of the model comparison results the research also shows that consumers in subsistence marketplaces are not just motivated by functionality and economic needs. If organizations cannot enhance the hedonic attributes of a pro-poor innovation, and reduce the internal/external constraints related to adoption of that pro-poor innovation, then adoption intention by consumers will be lower

Entwicklung eines Instruktionsvideos für die Untersuchung von Patienten mit Verdacht auf craniomandibuläre Dysfunktion

Objectives: The aim of this project was to develop an instructional video that demonstrates a standardized clinical examination on patients with suspected temporomandibular disorders (TMD). After viewing the video, the learner should be knowledgeable about the examination steps and application of the examination techniques. Methods: The instructional video was created by two dentists who are experienced in assessing patients with suspected TMD. Additionally, both examiners were calibrated according to the Diagnostic Criteria for Temporomandibular Disorders (DC/TMD). The instructional video was divided into chapters. Various camera angles, key points, image enlargements, and replays were used to better depict essential aspects of the assessment. Background noise was reduced to a minimum. Results: The instructional video was modified and completed in two phases: the first by an experienced dentist and the second by a dentist specialized in TMD. The final video includes nine chapters and is 26.5 minutes in length (https://doi.org/10.5061/dryad.k8r7qc1). Conclusion: Divided into chapters, this German instructional video shows an optimally timed, standardized clinical assessment of patients with suspected TMD.Zielsetzung: Ziel dieser Arbeit war die Erstellung eines Instruktionsvideos, welches das Erlernen der Methodik zur Untersuchung von Patienten mit Verdacht auf craniomandibuläre Dysfunktionen (CMD) unterstützen soll. Nach Betrachten des Videos sollte der Lernende den Ablauf einer Untersuchung und die Anwendung der Untersuchungstechniken kennen.Methodik: Ein Instruktionsvideo wurde von zwei Zahnärzten, welche in der Befunderhebung von Patienten mit Verdacht auf CMD erfahren sind, angefertigt. Zusätzlich waren beide Untersucher gemäß der Diagnostic Criteria for Temporomandibular Disorders (DC/TMD) kalibriert. Das Instruktionsvideo wurde in Kapiteln angelegt. Für eine verbesserte Darstellung wesentlicher Aspekte der Befunderhebung wurden verschiedene Kameraperspektiven, Stichpunkte, Bildvergrößerungen und Wiederholungen der Inhalte verwendet. Hintergrundgeräusche wurden auf ein Minimum reduziert.Ergebnisse: Mittels zweier Evaluationsphasen, wobei die erste durch erfahrene und die zweite durch auf CMD-spezialisierte Zahnärzte erfolgte, wurde das Instruktionsvideo sukzessive modifiziert und fertiggestellt. Das finale Video umfasst neun Kapitel und hat eine Gesamtdauer von 26,5 Minuten (https://doi.org/10.5061/dryad.k8r7qc1).Schlussfolgerung: Das deutsche Instruktionsvideo stellt den zeitlich optimierten Ablauf einer standardisierten Befunderhebung in Kapiteln dar, welche bei Patienten mit Verdacht auf craniomandibuläre Dysfunktion angewendet werden kann