iTReX: Interactive exploration of mono- and combination therapy dose response profiling data

High throughput screening methods, measuring the sensitivity and resistance of tumor cells to drug treatments have been rapidly evolving. Not only do these screens allow correlating response profiles to tumor genomic features for developing novel predictors of treatment response, but they can also add evidence for therapy decision making in precision oncology. Recent analysis methods developed for either assessing single agents or combination drug efficacies enable quantification of dose-response curves with restricted symmetric fit settings. Here, we introduce iTReX, a user-friendly and interactive Shiny/R application, for both the analysis of mono- and combination therapy responses. The application features an extended version of the drug sensitivity score (DSS) based on the integral of an advanced five-parameter dose-response curve model and a differential DSS for combination therapy profiling. Additionally, iTReX includes modules that visualize drug target interaction networks and support the detection of matches between top therapy hits and the sample omics features to enable the identification of druggable targets and biomarkers. iTReX enables the analysis of various quantitative drug or therapy response readouts (e.g. luminescence, fluorescence microscopy) and multiple treatment strategies (drug treatments, radiation). Using iTReX we validate a cost-effective drug combination screening approach and reveal the application’s ability to identify potential sample-specific biomarkers based on drug target interaction networks. The iTReX web application is accessible at (https://itrex.kitz-heidelberg.de).Peer reviewe

The benefits of in silico modeling to identify possible small-molecule drugs and their off-target interactions

Accepted for publication in a future issue of Future Medicinal Chemistry.The research into the use of small molecules as drugs continues to be a key driver in the development of molecular databases, computer-aided drug design software and collaborative platforms. The evolution of computational approaches is driven by the essential criteria that a drug molecule has to fulfill, from the affinity to targets to minimal side effects while having adequate absorption, distribution, metabolism, and excretion (ADME) properties. A combination of ligand- and structure-based drug development approaches is already used to obtain consensus predictions of small molecule activities and their off-target interactions. Further integration of these methods into easy-to-use workflows informed by systems biology could realize the full potential of available data in the drug discovery and reduce the attrition of drug candidates.Peer reviewe

Evaluation of Evidence-Based Practices in Online Learning: A Meta-Analysis and Review of Online Learning Studies

A systematic search of the research literature from 1996 through July 2008 identified more than a thousand empirical studies of online learning. Analysts screened these studies to find those that (a) contrasted an online to a face-to-face condition, (b) measured student learning outcomes, (c) used a rigorous research design, and (d) provided adequate information to calculate an effect size. As a result of this screening, 51 independent effects were identified that could be subjected to meta-analysis. The meta-analysis found that, on average, students in online learning conditions performed better than those receiving face-to-face instruction. The difference between student outcomes for online and face-to-face classes—measured as the difference between treatment and control means, divided by the pooled standard deviation—was larger in those studies contrasting conditions that blended elements of online and face-to-face instruction with conditions taught entirely face-to-face. Analysts noted that these blended conditions often included additional learning time and instructional elements not received by students in control conditions. This finding suggests that the positive effects associated with blended learning should not be attributed to the media, per se. An unexpected finding was the small number of rigorous published studies contrasting online and face-to-face learning conditions for K–12 students. In light of this small corpus, caution is required in generalizing to the K–12 population because the results are derived for the most part from studies in other settings (e.g., medical training, higher education)

Keystroke Biometrics in Response to Fake News Propagation in a Global Pandemic

This work proposes and analyzes the use of keystroke biometrics for content de-anonymization. Fake news have become a powerful tool to manipulate public opinion, especially during major events. In particular, the massive spread of fake news during the COVID-19 pandemic has forced governments and companies to fight against missinformation. In this context, the ability to link multiple accounts or profiles that spread such malicious content on the Internet while hiding in anonymity would enable proactive identification and blacklisting. Behavioral biometrics can be powerful tools in this fight. In this work, we have analyzed how the latest advances in keystroke biometric recognition can help to link behavioral typing patterns in experiments involving 100,000 users and more than 1 million typed sequences. Our proposed system is based on Recurrent Neural Networks adapted to the context of content de-anonymization. Assuming the challenge to link the typed content of a target user in a pool of candidate profiles, our results show that keystroke recognition can be used to reduce the list of candidate profiles by more than 90%. In addition, when keystroke is combined with auxiliary data (such as location), our system achieves a Rank-1 identification performance equal to 52.6% and 10.9% for a background candidate list composed of 1K and 100K profiles, respectively.Comment: arXiv admin note: text overlap with arXiv:2004.0362

PeptiCKDdb-peptide- and protein-centric database for the investigation of genesis and progression of chronic kidney disease

The peptiCKDdb is a publicly available database platform dedicated to support research in the field of chronic kidney disease (CKD) through identification of novel biomarkers and molecular features of this complex pathology. PeptiCKDdb collects peptidomics and proteomics datasets manually extracted from published studies related to CKD. Datasets from peptidomics or proteomics, human case/control studies on CKD and kidney or urine profiling were included. Data from 114 publications (studies of body fluids and kidney tissue: 26 peptidomics and 76 proteomics manuscripts on human CKD, and 12 focusing on healthy proteome profiling) are currently deposited and the content is quarterly updated. Extracted datasets include information about the experimental setup, clinical study design, discovery-validation sample sizes and list of differentially expressed proteins (P-value < 0.05). A dedicated interactive web interface, equipped with multiparametric search engine, data export and visualization tools, enables easy browsing of the data and comprehensive analysis. In conclusion, this repository might serve as a source of data for integrative analysis or a knowledgebase for scientists seeking confirmation of their findings and as such, is expected to facilitate the modeling of molecular mechanisms underlying CKD and identification of biologically relevant biomarkers.Database URL: www.peptickddb.com