Characterization of time-variant and time-invariant assessment of suicidality on Reddit using C-SSRS.
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ABSTRACT:
SUBMITTER: Gaur M
PROVIDER: S-EPMC8128252 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundIn recent years, both suicide and overdose rates have been increasing. Many individuals who struggle with opioid use disorder are prone to suicidal ideation; this may often result in overdose. However, these fatal overdoses are difficult to classify as intentional or unintentional. Intentional overdose is difficult to detect, partially due to the lack of predictors and social stigmas that push individuals away from seeking help. These individuals may instead use web-based means to articulate their concerns.ObjectiveThis study aimed to extract posts of suicidality among opioid users on Reddit using machine learning methods. The performance of the models is derivative of the data purity, and the results will help us to better understand the rationale of these users, providing new insights into individuals who are part of the opioid epidemic.MethodsReddit posts between June 2017 and June 2018 were collected from r/suicidewatch, r/depression, a set of opioid-related subreddits, and a control subreddit set. We first classified suicidal versus nonsuicidal languages and then classified users with opioid usage versus those without opioid usage. Several traditional baselines and neural network (NN) text classifiers were trained using subreddit names as the labels and combinations of semantic inputs. We then attempted to extract out-of-sample data belonging to the intersection of suicide ideation and opioid abuse. Amazon Mechanical Turk was used to provide labels for the out-of-sample data.ResultsClassification results were at least 90% across all models for at least one combination of input; the best classifier was convolutional neural network, which obtained an F1 score of 96.6%. When predicting out-of-sample data for posts containing both suicidal ideation and signs of opioid addiction, NN classifiers produced more false positives and traditional methods produced more false negatives, which is less desirable for predicting suicidal sentiments.ConclusionsOpioid abuse is linked to the risk of unintentional overdose and suicide risk. Social media platforms such as Reddit contain metadata that can aid machine learning and provide information at a personal level that cannot be obtained elsewhere. We demonstrate that it is possible to use NNs as a tool to predict an out-of-sample target with a model built from data sets labeled by characteristics we wish to distinguish in the out-of-sample target.
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Project description:Non-genotoxic hepatocarcinogens (NGHCs) can only be confirmed by 2-year rodent studies. Toxicogenomics (TGx) approaches using gene expression profiles from short-term animal studies could enable early assessment of NGHCs. However, high variance in the modulation of the genes had been noted among exposure styles and datasets. Expanding from our previous strategy in identifying consensus biomarkers in multiple experiments, we aimed to identify time-invariant biomarkers for NGHCs in short-term exposure styles and validate their applicability to long-term exposure styles. In this study, nine time-invariant biomarkers, namely A2m, Akr7a3, Aqp7, Ca3, Cdc2a, Cdkn3, Cyp2c11, Ntf3, and Sds, were identified from four large-scale microarray datasets. Machine learning techniques were subsequently employed to assess the prediction performance of the biomarkers. The biomarker set along with the Random Forest models gave the highest median area under the receiver operating characteristic curve (AUC) of 0.824 and a low interquartile range (IQR) variance of 0.036 based on a leave-one-out cross-validation. The application of the models to the external validation datasets achieved high AUC values of greater than or equal to 0.857. Enrichment analysis of the biomarkers inferred the involvement of chronic inflammatory diseases such as liver cirrhosis, fibrosis, and hepatocellular carcinoma in NGHCs. The time-invariant biomarkers provided a robust alternative for NGHC prediction.
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Project description:Understanding the impact of splicing and nonsense variants on RNA is crucial for the resolution of variant classification as well as their suitability for precision medicine interventions. This is primarily enabled through RNA studies involving transcriptomics followed by targeted assays using RNA isolated from clinically accessible tissues (CATs) such as blood or skin of affected individuals. Insufficient disease gene expression in CATs does however pose a major barrier to RNA based investigations, which we show is relevant to 1,436 Mendelian disease genes. We term these ‘silent’ Mendelian genes (SMGs), the largest portion (36%) of which are associated with neurological disorders. We developed two approaches to induce SMG expression in human dermal fibroblasts (HDFs) to overcome this limitation, including CRISPR-activation based gene transactivation, and fibroblast-to-neuron transdifferentiation. Initial transactivation screens involving 40 SMGs stimulated our development of a highly multiplexed transactivation system culminating in the 6- to 90,000-fold induction of expression of 20/20 (100%) SMGs tested in HDFs. Transdifferentiation of HDFs directly to neurons led to expression of 193/516 (37.4%) of SMGs implicated in neurological disease. The magnitude and isoform diversity of SMG expression following either transactivation or transdifferentiation was comparable to clinically relevant tissues. We apply transdifferentiation and/or gene transactivation combined with short- and long-read RNA sequencing to investigate the impact that variants in USH2A, SCN1A, DMD and PAK3 have on RNA using HDFs derived from affected individuals. Transactivation and transdifferentiation represent rapid, scalable functional genomic solutions to investigate variants impacting SMGs in the patient cell and genomic context.
2024-09-27 | GSE272900 | GEO
Project description:Aim. To develop a new invariant descriptor for the characterization of protein surfaces, suitable for various analysis tasks, such as protein functional classification, and search and retrieval of protein surfaces over a large database. Methods. We start with a local descriptor of selected circular patches on the protein surface. The descriptor records the distance distribution between the central residue and the residues within the patch, keeping track of the number of particular pairwise residue cooccurrences in the patch. A global descriptor for the entire protein surface is then constructed by combining information from the local descriptors. Our method is novel in its focus on residue-specific distance distributions, and the use of residue-distance co-occurrences as the basis for the proposed protein surface descriptors. Results. Results are presented for protein classification and for retrieval for three protein families. For the three families, we obtained an area under the curve for precision and recall ranging from 0.6494 (without residue co-occurrences) to 0.6683 (with residue co-occurrences). Large-scale screening using two other protein families placed related family members at the top of the rank, with a number of uncharacterized proteins also retrieved. Comparative results with other proposed methods are included.
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Project description:RNA variant assessment using transactivation and transdifferentiation
| PRJNA1139201 | ENA
Project description:Genome-wide association studies (GWAS) of suicidal thoughts and behaviors support the existence of genetic contributions. Continuous measures of psychiatric disorder symptom severity can sometimes model polygenic risk better than binarized definitions. We compared two severity measures of suicidal thoughts and behaviors at the molecular and functional levels using genome-wide data. We used summary association data from GWAS of four traits analyzed in 122,935 individuals of European ancestry: thought life was not worth living (TLNWL), thoughts of self-harm, actual self-harm, and attempted suicide. A new trait for suicidal thoughts and behaviors was constructed first, phenotypically, by aggregating the previous four traits (termed "suicidality") and second, genetically, by using genomic structural equation modeling (gSEM; termed S-factor). Suicidality and S-factor were compared using SNP-heritability (h2) estimates, genetic correlation (rg), partitioned h2, effect size distribution, transcriptomic correlations (ρGE) in the brain, and cross-population polygenic scoring (PGS). The S-factor had good model fit (χ2 = 0.21, AIC = 16.21, CFI = 1.00, SRMR = 0.024). Suicidality (h2 = 7.6%) had higher h2 than the S-factor (h2 = 2.54, Pdiff = 4.78 × 10-13). Although the S-factor had a larger number of non-null susceptibility loci (πc = 0.010), these loci had small effect sizes compared to those influencing suicidality (πc = 0.005, Pdiff = 0.045). The h2 of both traits was enriched for conserved biological pathways. The rg and ρGE support highly overlapping genetic and transcriptomic features between suicidality and the S-factor. PGS using European-ancestry SNP effect sizes strongly associated with TLNWL in Admixed Americans: Nagelkerke's R2 = 8.56%, P = 0.009 (PGSsuicidality) and Nagelkerke's R2 = 7.48%, P = 0.045 (PGSS-factor). An aggregate suicidality phenotype was statistically more heritable than the S-factor across all analyses and may be more informative for future genetic study designs interested in common genetic factors among different suicide related phenotypes.
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Project description:Fluctuations in the temporal durations of sensory signals constitute a major source of variability within natural stimulus ensembles. The neuronal mechanisms through which sensory systems can stabilize perception against such fluctuations are largely unknown. An intriguing instantiation of such robustness occurs in human speech perception, which relies critically on temporal acoustic cues that are embedded in signals with highly variable duration. Across different instances of natural speech, auditory cues can undergo temporal warping that ranges from 2-fold compression to 2-fold dilation without significant perceptual impairment. Here, we report that time-warp-invariant neuronal processing can be subserved by the shunting action of synaptic conductances that automatically rescales the effective integration time of postsynaptic neurons. We propose a novel spike-based learning rule for synaptic conductances that adjusts the degree of synaptic shunting to the temporal processing requirements of a given task. Applying this general biophysical mechanism to the example of speech processing, we propose a neuronal network model for time-warp-invariant word discrimination and demonstrate its excellent performance on a standard benchmark speech-recognition task. Our results demonstrate the important functional role of synaptic conductances in spike-based neuronal information processing and learning. The biophysics of temporal integration at neuronal membranes can endow sensory pathways with powerful time-warp-invariant computational capabilities.
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Project description:Within months of the COVID-19 pandemic being declared on March 20, 2020, novel, more infectious variants of SARS-CoV-2 began to be detected in geospatially distinct regions of the world. With international travel being a lead cause of spread of the disease, the importance of rapidly identifying variants entering a country is critical. In this study, we utilized wastewater-based epidemiology (WBE) to monitor the presence of variants in wastewater generated in managed COVID-19 quarantine facilities for international air passengers entering the United Kingdom. Specifically, we developed multiplex reverse transcription quantitative PCR (RT-qPCR) assays for the identification of defining mutations associated with Beta (K417N), Gamma (K417T), Delta (156/157DEL), and Kappa (E154K) variants which were globally prevalent at the time of sampling (April to July 2021). The assays sporadically detected mutations associated with the Beta, Gamma, and Kappa variants in 0.7%, 2.3%, and 0.4% of all samples, respectively. The Delta variant was identified in 13.3% of samples, with peak detection rates and concentrations observed in May 2021 (24%), concurrent with its emergence in the United Kingdom. The RT-qPCR results correlated well with those from sequencing, suggesting that PCR-based detection is a good predictor for variant presence; although, inadequate probe binding may lead to false positive or negative results. Our findings suggest that WBE coupled with RT-qPCR may be used as a rapid, initial assessment to identify emerging variants at international borders and mass quarantining facilities. IMPORTANCE With the global spread of COVID-19, it is essential to identify emerging variants which may be more harmful or able to escape vaccines rapidly. To date, the gold standard to assess variants circulating in communities has been the sequencing of the S gene or the whole genome of SARS-CoV-2; however, that approach is time-consuming and expensive. In this study, we developed two duplex RT-qPCR assays to detect and quantify defining mutations associated with the Beta, Gamma, Delta, and Kappa variants. The assays were validated using RNA extracts derived from wastewater samples taken at quarantine facilities. The results showed good correlation with the results of sequencing and demonstrated the emergence of the Delta variant in the United Kingdom in May 2021. The assays developed here enable the assessment of variant-specific mutations within 2 h after the RNA extract was generated which is essential for outbreak rapid response.
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Project description:Understanding the impact of splicing and nonsense variants on RNA is crucial for the resolution of variant classification as well as their suitability for precision medicine interventions. This is primarily enabled through RNA studies involving transcriptomics followed by targeted assays using RNA isolated from clinically accessible tissues (CATs) such as blood or skin of affected individuals. Insufficient disease gene expression in CATs does however pose a major barrier to RNA based investigations, which we show is relevant to 1,436 Mendelian disease genes. We term these "silent" Mendelian genes (SMGs), the largest portion (36%) of which are associated with neurological disorders. We developed two approaches to induce SMG expression in human dermal fibroblasts (HDFs) to overcome this limitation, including CRISPR-activation-based gene transactivation and fibroblast-to-neuron transdifferentiation. Initial transactivation screens involving 40 SMGs stimulated our development of a highly multiplexed transactivation system culminating in the 6- to 90,000-fold induction of expression of 20/20 (100%) SMGs tested in HDFs. Transdifferentiation of HDFs directly to neurons led to expression of 193/516 (37.4%) of SMGs implicated in neurological disease. The magnitude and isoform diversity of SMG expression following either transactivation or transdifferentiation was comparable to clinically relevant tissues. We apply transdifferentiation and/or gene transactivation combined with short- and long-read RNA sequencing to investigate the impact that variants in USH2A, SCN1A, DMD, and PAK3 have on RNA using HDFs derived from affected individuals. Transactivation and transdifferentiation represent rapid, scalable functional genomic solutions to investigate variants impacting SMGs in the patient cell and genomic context.
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Project description:Time unit invariance is introduced as an additional requirement for multiperiod risk measures: for a constant portfolio under an i.i.d. risk factor process, the multiperiod risk should equal the one period risk of the aggregated loss, for an appropriate choice of parameters and independent of the portfolio and its distribution. Multiperiod Maximum Loss over a sequence of Kullback-Leibler balls is time unit invariant. This is also the case for the entropic risk measure. On the other hand, multiperiod Value at Risk and multiperiod Expected Shortfall are not time unit invariant.
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