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  1. Abstract

    Approximately 10% of the world’s population is at risk of schistosomiasis, a disease of poverty caused by theSchistosomaparasite. To facilitate drug discovery for this complex flatworm, we developed an automated high-content screen to quantify the multidimensional responses ofSchistosoma mansonipost-infective larvae (somules) to chemical insult. We describe an integrated platform to process worms at scale, collect time-lapsed, bright-field images, segment highly variable and touching worms, and then store, visualize, and query dynamic phenotypes. To demonstrate the methodology, we treated somules with seven drugs that generated diverse responses and evaluated 45 static and kinetic response descriptors relative to concentration and time. For compound screening, we used the Mahalanobis distance to compare multidimensional phenotypic effects induced by 1323 approved drugs. Overall, we characterize both known anti-schistosomals and identify new bioactives. Apart from facilitating drug discovery, the multidimensional quantification provided by this platform will allow mapping of chemistry to phenotype.

     
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  2. Opioid addiction constitutes a significant contemporary health crisis that is multifarious in its complexity. Modeling the epidemiology of any addiction is challenging in its own right. For opioid addiction, the challenge is exacerbated due to the difficulties in collecting real-time data and the circumscribed nature of information opioid users may disclose owing to stigma associated with prescription misuse. Given this context, identifying the progression of individuals through the stages of (opioid) addiction is one of the more acute problems in epidemiological modeling whose solution is crucial for designing specific interventions at both personal and population levels. We describe a computational approach for determining and characterizing addiction stages of opioid users from their social media posts. The proposed approach combines recurrent neural network learning with information-theoretic analysis of word-associations and context-based word embedding to determine addiction stage-specific language usage. Users who have a high likelihood for relapsing back to drug-use are identified and characterized using propensity score matching and logistic regression. Experimental evaluations indicate that the proposed approach can distinguish between various addiction stages and identify users prone to relapse with high accuracy as evidenced by F1 scores of 0.88 and 0.79 respectively 
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  3. Wren, Jonathan (Ed.)
    Abstract Motivation Substance abuse constitutes one of the major contemporary health epidemics. Recently, the use of social media platforms has garnered interest as a novel source of data for drug addiction epidemiology. Often however, the language used in such forums comprises slang and jargon. Currently, there are no publicly available resources to automatically analyse the esoteric language-use in the social media drug-use sub-culture. This lacunae introduces critical challenges for interpreting, sensemaking and modeling of addiction epidemiology using social media. Results Drug-Use Insights (DUI) is a public and open-source web application to address the aforementioned deficiency. DUI is underlined by a hierarchical taxonomy encompassing 108 different addiction related categories consisting of over 9,000 terms, where each category encompasses a set of semantically related terms. These categories and terms were established by utilizing thematic analysis in conjunction with term embeddings generated from 7,472,545 Reddit posts made by 1,402,017 redditors. Given post(s) from social media forums such as Reddit and Twitter, DUI can be used foremost to identify constituent terms related to drug use. Furthermore, the DUI categories and integrated visualization tools can be leveraged for semantic- and exploratory analysis. To the best of our knowledge, DUI utilizes the largest number of substance use and recovery social media posts used in a study and represents the first significant online taxonomy of drug abuse terminology. Availability The DUI web server and source code are available at: http://haddock9.sfsu.edu/insight/ Supplementary information Supplementary data are available at Bioinformatics online. 
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  4. null (Ed.)
    Background: Addiction to drugs and alcohol constitutes one of the significant factors underlying the decline in life expectancy in the US. Several context-specific reasons influence drug use and recovery. In particular emotional distress, physical pain, relationships, and self-development efforts are known to be some of the factors associated with addiction recovery. Unfortunately, many of these factors are not directly observable and quantifying, and assessing their impact can be difficult. Based on social media posts of users engaged in substance use and recovery on the forum Reddit, we employed two psycholinguistic tools, Linguistic Inquiry and Word Count and Empath and activities of substance users on various Reddit sub-forums to analyze behavior underlining addiction recovery and relapse. We then employed a statistical analysis technique called structural equation modeling to assess the effects of these latent factors on recovery and relapse. Results: We found that both emotional distress and physical pain significantly influence addiction recovery behavior. Self-development activities and social relationships of the substance users were also found to enable recovery. Furthermore, within the context of self-development activities, those that were related to influencing the mental and physical well-being of substance users were found to be positively associated with addiction recovery. We also determined that lack of social activities and physical exercise can enable a relapse. Moreover, geography, especially life in rural areas, appears to have a greater correlation with addiction relapse. Conclusions: The paper describes how observable variables can be extracted from social media and then be used to model important latent constructs that impact addiction recovery and relapse. We also report factors that impact self-induced addiction recovery and relapse. To the best of our knowledge, this paper represents the first use of structural equation modeling of social media data with the goal of analyzing factors influencing addiction recovery. 
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  5. Advances in microscopy and high-content imaging now offer a powerful way to profile the phenotypic response of intact systems to molecular perturbation and study the response irrespective of putative target activity and by preserving the physiological context in the living systems. An emerging challenge in bioinformatics and drug discovery is constituted by data generated from such studies that involve analyzing the effect of specific molecules at the system-wide organism level. In this paper we propose a novel automated approach that combines techniques from biological imaging and machine learning to automatically quantify a fundamental measure of molecular perturbation in an intact biological system, namely, its dose-response characteristics. We validate our results using phenotypic assay data involving post-infective larvae (schistosomula) of the parasitic Schistosoma mansoni flatworm. This parasite is one of the etiological agents of schistosomiasis – a significant neglected tropical disease, which puts at-risk nearly two billion people. 
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