A bottleneck in drug discovery is the identification of the molecular targets of a compound (mode of action, MoA) and of its off-target effects. Previous approaches to elucidate drug MoA include analysis of chemical structures, transcriptional responses following treatment, and text mining. Methods based on transcriptional responses require the least amount of information and can be quickly applied to new compounds. Available methods are inefficient and are not able to support network pharmacology. We developed an automatic and robust approach that exploits similarity in gene expression profiles following drug treatment, across multiple cell lines and dosages, to predict similarities in drug effect and MoA. We constructed a "drug network" of 1,302 nodes (drugs) and 41,047 edges (indicating similarities between pair of drugs). We applied network theory, partitioning drugs into groups of densely interconnected nodes (i.e., communities). These communities are significantly enriched for compounds with similar MoA, or acting on the same pathway, and can be used to identify the compoundtargeted biological pathways. New compounds can be integrated into the network to predict their therapeutic and off-target effects. Using this network, we correctly predicted the MoA for nine anticancer compounds, and we were able to discover an unreported effect for a well-known drug. We verified an unexpected similarity between cyclin-dependent kinase 2 inhibitors and Topoisomerase inhibitors. We discovered that Fasudil (a Rho-kinase inhibitor) might be "repositioned" as an enhancer of cellular autophagy, potentially applicable to several neurodegenerative disorders. Our approach was implemented in a tool (Mode of Action by NeTwoRk Analysis, MANTRA, http://mantra.tigem.it).computational drug discovery | drug repurposing | systems biology | chemotherapy

The problem of Multiple Object Tracking (MOT) consists in following the trajectory of different objects in a sequence, usually a video. In recent years, with the rise of Deep Learning, the algorithms that provide a solution to this problem have benefited from the representational power of deep models. This paper provides a comprehensive survey on works that employ Deep Learning models to solve the task of MOT on single-camera videos. Four main steps in MOT algorithms are identified, and an in-depth review of how Deep Learning was employed in each one of these stages is presented. A complete experimental comparison of the presented works on the three MOTChallenge datasets is also provided, identifying a number of similarities among the top-performing methods and presenting some possible future research directions.In this section, a general description about the problem of MOT is provided. The main characteristics and common steps of MOT algorithms are identified and described in section 2.1. The metrics that are usually employed to evaluate the performance of the models are discussed in section 2.2, while the most important benchmark datasets are presented in section 2.3. 7 The website says the detections were obtained using a model based on a latent SVM, or L-SVM. That model is now known as Deformable Parts Model (DPM). 8

Existing computational methods for drug repositioning either rely only on the gene expression response of cell lines after treatment, or on drug-to-disease relationships, merging several information levels. However, the noisy nature of the gene expression and the scarcity of genomic data for many diseases are important limitations to such approaches. Here we focused on a drug-centered approach by predicting the therapeutic class of FDA-approved compounds, not considering data concerning the diseases. We propose a novel computational approach to predict drug repositioning based on state-of-the-art machine-learning algorithms. We have integrated multiple layers of information: i) on the distances of the drugs based on how similar are their chemical structures, ii) on how close are their targets within the protein-protein interaction network, and iii) on how correlated are the gene expression patterns after treatment. Our classifier reaches high accuracy levels (78%), allowing us to re-interpret the top misclassifications as re-classifications, after rigorous statistical evaluation. Efficient drug repurposing has the potential to significantly impact the whole field of drug development. The results presented here can significantly accelerate the translation into the clinics of known compounds for novel therapeutic uses.

Drug repurposing involves the identification of new applications for existing drugs at a lower cost and in a shorter time. There are different computational drug-repurposing strategies and some of these approaches have been applied to the coronavirus disease 2019 (COVID-19) pandemic. Computational drug-repositioning approaches applied to COVID-19 can be broadly categorized into (i) network-based models, (ii) structure-based approaches and (iii) artificial intelligence (AI) approaches. Network-based approaches are divided into two categories: network-based clustering approaches and network-based propagation approaches. Both of them allowed to annotate some important patterns, to identify proteins that are functionally associated with COVID-19 and to discover novel drug–disease or drug–target relationships useful for new therapies. Structure-based approaches allowed to identify small chemical compounds able to bind macromolecular targets to evaluate how a chemical compound can interact with the biological counterpart, trying to find new applications for existing drugs. AI-based networks appear, at the moment, less relevant since they need more data for their application.

Abstract.We have carried out a multifrequency analysis of the radio variability of blazars, exploiting the data obtained during the extensive monitoring programs carried out at the University of Michigan Radio Astronomy Observatory (UMRAO, at 4.8, 8, and 14.5 GHz) and at the Metsähovi Radio Observatory (22 and 37 GHz). Two different techniques detect, in the Metsähovi light curves, evidence of periodicity at both frequencies for 5 sources (0224 + 671, 0945 + 408, 1226 + 023, 2200 + 420, and 2251 + 158). For the last three sources, consistent periods are found also at the three UMRAO frequencies and the Scargle (1982) method yields an extremely low false-alarm probability. On the other hand, the 22 and 37 GHz periodicities of 0224+671 and 0945 + 408 (which were less extensively monitored at Metsähovi and for which we get a significant false-alarm probability) are not confirmed by the UMRAO database, where some indications of ill-defined periods of about a factor of two longer are retrieved. We have also investigated the variability index, the structure function, and the distribution of intensity variations of the most extensively monitored sources. We find a statistically significant difference in the distribution of the variability index for BL Lac objects compared to flat-spectrum radio quasars (FSRQs), in the sense that the former objects are more variable. For both populations the variability index steadily increases with increasing frequency. The distribution of intensity variations also broadens with increasing frequency, and approaches a log-normal shape at the highest frequencies. We find that variability enhances by 20-30% the high frequency counts of extragalactic radio-sources at bright flux densities, such as those of the WMAP and P surveys. In all objects with detected periodicity we find evidence for the existence of impulsive signals superimposed on the periodic component.