Network Analysis of Differential Expression for the Identification of Disease-Causing Genes

Genetic studies (in particular linkage and association studies) identify chromosomal regions involved in a disease or phenotype of interest, but those regions often contain many candidate genes, only a few of which can be followed-up for biological validation. Recently, computational methods to identify (prioritize) the most promising candidates within a region have been proposed, but they are usually not applicable to cases where little is known about the phenotype (no or few confirmed disease genes, fragmentary understanding of the biological cascades involved). We seek to overcome this limitation by replacing knowledge about the biological process by experimental data on differential gene expression between affected and healthy individuals. Considering the problem from the perspective of a gene/protein network, we assess a candidate gene by considering the level of differential expression in its neighborhood under the assumption that strong candidates will tend to be surrounded by differentially expressed neighbors. We define a notion of soft neighborhood where each gene is given a contributing weight, which decreases with the distance from the candidate gene on the protein network. To account for multiple paths between genes, we define the distance using the Laplacian exponential diffusion kernel. We score candidates by aggregating the differential expression of neighbors weighted as a function of distance. Through a randomization procedure, we rank candidates by p-values. We illustrate our approach on four monogenic diseases and successfully prioritize the known disease causing genes

Digital Assessment Tools Using Animation Features to Quantify Alcohol Consumption: Systematic App Store and Literature Review (Preprint)

BACKGROUND Accurate and user-friendly assessment tools for quantifying alcohol consumption are a prerequisite for effective interventions to reduce alcohol-related harm. Digital assessment tools (DATs) that allow the description of consumed alcoholic drinks through animation features may facilitate more accurate reporting than conventional approaches. OBJECTIVE This review aims to identify and characterize freely available DATs in English or Russian that use animation features to support the quantitative assessment of alcohol consumption (alcohol DATs) and determine the extent to which such tools have been scientifically evaluated in terms of feasibility, acceptability, and validity. METHODS Systematic English and Russian searches were conducted in iOS and Android app stores and via the Google search engine. Information on the background and content of eligible DATs was obtained from app store descriptions, websites, and test completions. A systematic literature review was conducted in Embase, MEDLINE, PsycINFO, and Web of Science to identify English-language studies reporting the feasibility, acceptability, and validity of animation-using alcohol DATs. Where possible, the evaluated DATs were accessed and assessed. Owing to the high heterogeneity of study designs, results were synthesized narratively. RESULTS We identified 22 eligible alcohol DATs in English, 3 (14%) of which were also available in Russian. More than 95% (21/22) of tools allowed the choice of a beverage type from a visually displayed selection. In addition, 36% (8/22) of tools enabled the choice of a drinking vessel. Only 9% (2/22) of tools allowed the simulated interactive pouring of a drink. For none of the tools published evaluation studies were identified in the literature review. The systematic literature review identified 5 exploratory studies evaluating the feasibility, acceptability, and validity of 4 animation-using alcohol DATs, 1 (25%) of which was available in the searched app stores. The evaluated tools reached moderate to high scores on user rating scales and showed fair to high convergent validity when compared with established assessment methods. CONCLUSIONS Animation-using alcohol DATs are available in app stores and on the web. However, they often use nondynamic features and lack scientific background information. Explorative study data suggest that such tools might enable the user-friendly and valid assessment of alcohol consumption and could thus serve as a building block in the reduction of alcohol-attributable health burden worldwide. </sec

Digital assessment tools using animation features to quantify alcohol consumption: systematic app store and literature review.

BACKGROUND: Accurate and user-friendly assessment tools for quantifying alcohol consumption are a prerequisite for effective interventions to reduce alcohol-related harm. Digital assessment tools (DATs) that allow the description of consumed alcoholic drinks through animation features may facilitate more accurate reporting than conventional approaches. OBJECTIVE: This review aims to identify and characterize freely available DATs in English or Russian that use animation features to support the quantitative assessment of alcohol consumption (alcohol DATs) and determine the extent to which such tools have been scientifically evaluated in terms of feasibility, acceptability, and validity. METHODS: Systematic English and Russian searches were conducted in iOS and Android app stores and via the Google search engine. Information on the background and content of eligible DATs was obtained from app store descriptions, websites, and test completions. A systematic literature review was conducted in Embase, MEDLINE, PsycINFO, and Web of Science to identify English-language studies reporting the feasibility, acceptability, and validity of animation-using alcohol DATs. Where possible, the evaluated DATs were accessed and assessed. Owing to the high heterogeneity of study designs, results were synthesized narratively. RESULTS: We identified 22 eligible alcohol DATs in English, 3 (14%) of which were also available in Russian. More than 95% (21/22) of tools allowed the choice of a beverage type from a visually displayed selection. In addition, 36% (8/22) of tools enabled the choice of a drinking vessel. Only 9% (2/22) of tools allowed the simulated interactive pouring of a drink. For none of the tools published evaluation studies were identified in the literature review. The systematic literature review identified 5 exploratory studies evaluating the feasibility, acceptability, and validity of 4 animation-using alcohol DATs, 1 (25%) of which was available in the searched app stores. The evaluated tools reached moderate to high scores on user rating scales and showed fair to high convergent validity when compared with established assessment methods. CONCLUSIONS: Animation-using alcohol DATs are available in app stores and on the web. However, they often use nondynamic features and lack scientific background information. Explorative study data suggest that such tools might enable the user-friendly and valid assessment of alcohol consumption and could thus serve as a building block in the reduction of alcohol-attributable health burden worldwide

Digital Assessment Tools Using Animation Features to Quantify Alcohol Consumption: Systematic App Store and Literature Review

Background Accurate and user-friendly assessment tools for quantifying alcohol consumption are a prerequisite for effective interventions to reduce alcohol-related harm. Digital assessment tools (DATs) that allow the description of consumed alcoholic drinks through animation features may facilitate more accurate reporting than conventional approaches. Objective This review aims to identify and characterize freely available DATs in English or Russian that use animation features to support the quantitative assessment of alcohol consumption (alcohol DATs) and determine the extent to which such tools have been scientifically evaluated in terms of feasibility, acceptability, and validity. Methods Systematic English and Russian searches were conducted in iOS and Android app stores and via the Google search engine. Information on the background and content of eligible DATs was obtained from app store descriptions, websites, and test completions. A systematic literature review was conducted in Embase, MEDLINE, PsycINFO, and Web of Science to identify English-language studies reporting the feasibility, acceptability, and validity of animation-using alcohol DATs. Where possible, the evaluated DATs were accessed and assessed. Owing to the high heterogeneity of study designs, results were synthesized narratively. Results We identified 22 eligible alcohol DATs in English, 3 (14%) of which were also available in Russian. More than 95% (21/22) of tools allowed the choice of a beverage type from a visually displayed selection. In addition, 36% (8/22) of tools enabled the choice of a drinking vessel. Only 9% (2/22) of tools allowed the simulated interactive pouring of a drink. For none of the tools published evaluation studies were identified in the literature review. The systematic literature review identified 5 exploratory studies evaluating the feasibility, acceptability, and validity of 4 animation-using alcohol DATs, 1 (25%) of which was available in the searched app stores. The evaluated tools reached moderate to high scores on user rating scales and showed fair to high convergent validity when compared with established assessment methods. Conclusions Animation-using alcohol DATs are available in app stores and on the web. However, they often use nondynamic features and lack scientific background information. Explorative study data suggest that such tools might enable the user-friendly and valid assessment of alcohol consumption and could thus serve as a building block in the reduction of alcohol-attributable health burden worldwide. Trial Registration PROSPERO International Prospective Register of Systematic Reviews CRD42020172825; https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020172825 </jats:sec

Identification of DAGLA as an autoantibody target in cerebellar ataxia

Background We aimed to investigate the clinical, imaging and fluid biomarker characteristics in patients with antidiacylglycerol lipase alpha (DAGLA)-autoantibody-associated cerebellitis.Methods Serum and cerebrospinal fliud (CSF) samples from four index patients were subjected to comprehensive autoantibody screening by indirect immunofluorescence assay (IIFA). Immunoprecipitation, mass spectrometry and recombinant protein assays were used to identify the autoantigen. Sera from 101 patients with various neurological symptoms and a similar tissue staining pattern as the index patient samples, and 102 healthy donors were analysed in recombinant cell-based IIFA (RC-IIFA) with the identified protein. Epitope characterisation of all positive samples was performed via ELISA, immunoblot, immunoprecipitation and RC-IIFA using different DAGLA fragments.Results All index patients were relatively young (age: 18-34) and suffered from pronounced gait ataxia, dysarthria and visual impairments. Paraclinical hallmarks in early-stage disease were inflammatory CSF changes and cerebellar cortex hyperintensity in MRI. Severe cerebellar atrophy developed in three of four patients within 6 months. All patient samples showed the same unclassified IgG reactivity with the cerebellar molecular layer. DAGLA was identified as the target antigen and confirmed by competitive inhibition experiments and DAGLA-specific RC-IIFA. In RC-IIFA, serum reactivity against DAGLA was also found in 17/101 disease controls, including patients with different clinical phenotypes than the one of the index patients, and in 1/102 healthy donors. Epitope characterisation revealed that 17/18 anti-DAGLA-positive control sera reacted with a C-terminal intracellular DAGLA 583-1042 fragment, while the CSF samples of the index patients targeted a conformational epitope between amino acid 1 and 157.Conclusions We propose that anti-DAGLA autoantibodies detected in CSF, with a characteristic tissue IIFA pattern, represent novel biomarkers for rapidly progressive cerebellitis