scholarly journals Gene-Wise Burden of Coding Variants Correlates to Noncoding Pharmacogenetic Risk Variants

2020 ◽  
Vol 21 (9) ◽  
pp. 3091 ◽  
Author(s):  
Jihye Park ◽  
Soo Youn Lee ◽  
Su Youn Baik ◽  
Chan Hee Park ◽  
Jun Hee Yoon ◽  
...  
Keyword(s):  
Protein Function ◽  
Drug Level ◽  
Operating Characteristics ◽  
Common Coding ◽  
1000 Genomes ◽  
Risk Variants ◽  
Receiver Operating Characteristics Curve ◽  
Gene Level ◽  
Noncoding Variant ◽  
Coding Variants

Genetic variability can modulate individual drug responses. A significant portion of pharmacogenetic variants reside in the noncoding genome yet it is unclear if the noncoding variants directly influence protein function and expression or are present on a haplotype including a functionally relevant genetic variation (synthetic association). Gene-wise variant burden (GVB) is a gene-level measure of deleteriousness, reflecting the cumulative effects of deleterious coding variants, predicted in silico. To test potential associations between noncoding and coding pharmacogenetic variants, we computed a drug-level GVB for 5099 drugs from DrugBank for 2504 genomes of the 1000 Genomes Project and evaluated the correlation between the long-known noncoding variant-drug associations in PharmGKB, with functionally relevant rare and common coding variants aggregated into GVBs. We obtained the area under the receiver operating characteristics curve (AUC) by comparing the drug-level GVB ranks against the corresponding pharmacogenetic variants-drug associations in PharmGKB. We obtained high overall AUCs (0.710 ± 0.022–0.734 ± 0.018) for six different methods (i.e., SIFT, MutationTaster, Polyphen-2 HVAR, Polyphen-2 HDIV, phyloP, and GERP++), and further improved the ethnicity-specific validations (0.759 ± 0.066–0.791 ± 0.078). These results suggest that a significant portion of the long-known noncoding variant-drug associations can be explained as synthetic associations with rare and common coding variants burden of the corresponding pharmacogenes.

scholarly journals Etiological Work-Up for Adults with Bronchiectasis: A Predictive Diagnostic Score for Primary Ciliary Dyskinesia and Cystic Fibrosis

2021 ◽  
Vol 10 (16) ◽  
pp. 3478
Author(s):  
Frederic Schlemmer ◽  
Agnes Hamzaoui ◽  
Sonia Zebachi ◽  
Aurelie Le Thuaut ◽  
Gilles Mangiapan ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Primary Ciliary Dyskinesia ◽  
Clinical Score ◽  
Adult Patients ◽  
Operating Characteristics ◽  
Diagnostic Score ◽  
Receiver Operating Characteristics Curve ◽  
Diagnostic Work ◽  
Work Up ◽  
Ciliary Dyskinesia

Background: etiological investigations are not done for all adult patients with bronchiectasis because of the availability and interpretation of tests. The aim of the study was to elaborate a score to identify patients at high risk of having cystic fibrosis or primary ciliary dyskinesia (CF/PCD), which require appropriate management. Methods: diagnostic work-ups were carried out on a French monocenter cohort, and results were subjected to logistic-regression analyses to identify the independent factors associated with CF/PCD diagnosis and, thereby, elaborate a score to validate in a second cohort. Results: among 188 patients, 158 had no obvious diagnosis and were enrolled in the algorithm-construction group. In multivariate analyses, age at symptom onset (8.69 (2.10–35.99); p = 0.003), chronic ENT symptoms or diagnosed sinusitis (10.53 (1.26–87.57); p = 0.03), digestive symptoms or situs inversus (5.10 (1.23–21.14); p = 0.025), and Pseudomonas. aeruginosa and/or Staphylococcus aureus isolated from sputum (11.13 (1.34–92.21); p = 0.02) are associated with CF or PCD. Receiver operating characteristics curve analysis, using a validation group of 167 patients with bronchiectasis, confirmed the score’s performance with AUC 0.92 (95% CI: 0.84–0.98). Conclusions: a clinical score may help identify adult patients with bronchiectasis at higher risk of having CF or PCD.

scholarly journals Evaluating the Risk of Tumors Diseases Based on Measurement of Urinary and Serumal Antioxidants Using the New Agar Diffusion Methods

2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Ying Zhou ◽  
Jing Chen ◽  
Zhen Wang ◽  
Hui Liu
Keyword(s):  
Antioxidant Capacity ◽  
Healthy People ◽  
Healthy Individuals ◽  
Operating Characteristics ◽  
Tumor Patients ◽  
Tumor Diseases ◽  
Receiver Operating Characteristics Curve ◽  
Age Range ◽  
Urine And Serum ◽  
Effect Of Age

Objectives. To discuss the characteristics of the amount of urinary total antioxidants in tumor diseases and the possibility of utilizing the changing regulation of urinary antioxidants to diagnose tumor diseases.Method. Urine and serum specimens from 130 healthy people were used to investigate the variation of antioxidant capacity against age. Urine and serum specimens from 44 unselected patients with tumors and 44 healthy people with same age background were used to explore the significance of urinary antioxidant capacity in clinic to diagnose tumor diseases. Potassium permanganate agar method and iodine starch method were used to determine the amount of total antioxidants.Results. In healthy people, more antioxidants in urine were measured in older people, while the results were opposite in serum. More antioxidants were found in urine of tumor patients than in healthy people with same age-range.Conclusions. According to the results of 130 measurements, the amount of antioxidants in urine varies by age. By using agar methods to measure antioxidants, the effect of age is required to be considered. Antioxidants levels from tumor patients were significantly higher than healthy individuals in urine. The combination of urine and serum to determine total antioxidants can better diagnose tumor diseases based on iodine starch method, with area under the receiver operating characteristics curve at 0.787.

scholarly journals DeepIsoFun: a deep domain adaptation approach to predict isoform functions

2018 ◽  
Vol 35 (15) ◽  
pp. 2535-2544 ◽  
Author(s):  
Dipan Shaw ◽  
Hao Chen ◽  
Tao Jiang
Keyword(s):  
Network Architecture ◽  
Domain Adaptation ◽  
Multiple Instance Learning ◽  
Training Data ◽  
Supplementary Information ◽  
Operating Characteristics ◽  
Neural Network Architecture ◽  
Receiver Operating Characteristics Curve ◽  
Gene Functions ◽  
Better Than

AbstractMotivationIsoforms are mRNAs produced from the same gene locus by alternative splicing and may have different functions. Although gene functions have been studied extensively, little is known about the specific functions of isoforms. Recently, some computational approaches based on multiple instance learning have been proposed to predict isoform functions from annotated gene functions and expression data, but their performance is far from being desirable primarily due to the lack of labeled training data. To improve the performance on this problem, we propose a novel deep learning method, DeepIsoFun, that combines multiple instance learning with domain adaptation. The latter technique helps to transfer the knowledge of gene functions to the prediction of isoform functions and provides additional labeled training data. Our model is trained on a deep neural network architecture so that it can adapt to different expression distributions associated with different gene ontology terms.ResultsWe evaluated the performance of DeepIsoFun on three expression datasets of human and mouse collected from SRA studies at different times. On each dataset, DeepIsoFun performed significantly better than the existing methods. In terms of area under the receiver operating characteristics curve, our method acquired at least 26% improvement and in terms of area under the precision-recall curve, it acquired at least 10% improvement over the state-of-the-art methods. In addition, we also study the divergence of the functions predicted by our method for isoforms from the same gene and the overall correlation between expression similarity and the similarity of predicted functions.Availability and implementationhttps://github.com/dls03/DeepIsoFun/Supplementary informationSupplementary data are available at Bioinformatics online.

scholarly journals Reduced Superficial Capillary Density in Cerebral Infarction Is Inversely Correlated With the NIHSS Score

2021 ◽  
Vol 13 ◽  
Author(s):  
William Robert Kwapong ◽  
Yuying Yan ◽  
Zilong Hao ◽  
Bo Wu
Keyword(s):  
Cerebral Infarction ◽  
Capillary Density ◽  
Foveal Avascular Zone ◽  
Healthy Controls ◽  
Operating Characteristics ◽  
Microvascular Changes ◽  
Receiver Operating Characteristics Curve ◽  
Capillary Plexus ◽  
Magnetic Resonance Imaging Mri

Purpose: The retina and the brain share similar neuronal and microvascular features, therein we aimed to assess the structural and microvascular changes in the macula and choriocapillaris (CC) in patients with cerebral infarction when compared with healthy controls using optical coherence tomography angiography (OCTA).Methods: OCTA was used to image and measure the capillary density in the radial peripapillary capillaries (RPC), superficial capillary plexus (SCP), deep capillary plexus (DCP), choriocapillaris (CC), and mean area of the foveal avascular zone (FAZ) in all participants. Twenty-two cerebral infarction patients based on their magnetic resonance imaging (MRI) and 25 healthy controls were included in our study.Results: Density of the RPC (P < 0.001), SCP (P = 0.001), DCP (P < 0.001) and CC (P < 0.001) were significantly reduced in cerebral infarction patients when compared with healthy controls, respectively. Retinal thickness measurements (P < 0.05) were significantly reduced in cerebral infarction patients when compared with healthy controls. The mean FAZ area was significantly larger (P = 0.012) in cerebral infarction patients when compared with healthy controls. National Institute of HealthStroke Scale (NIHSS) inversely correlated with SCP density in cerebral infarction patients (Rho = −0.409, P = 0.001). Receiver operating characteristics curve analysis showed that the blood flow of the choriocapillaris had the highest index [area under the receiver operatingcharacteristic (AUROC) = 0.964] to discriminate cerebral infarction patients from the healthy controls.Conclusions: Our study suggests that cerebral microcirculation dysfunction which occurs in cerebral infarction is mirrored in the macula and choroidal microcirculation. OCTA has the potential to non-invasively characterize the macula and choroidal changes in cerebral infarction in vivo.

scholarly journals A pilot study of discovery and validation of peritoneal endometriosis biomarkers in peritoneal fluid and serum

2020 ◽  
Author(s):  
See Ling Loy ◽  
Jieliang Zhou ◽  
Liang Cui ◽  
Tse Yeun Tan ◽  
Tat Xin Ee ◽  
...  
Keyword(s):  
Peritoneal Fluid ◽  
Liquid Chromatography Mass Spectrometry ◽  
Operating Characteristics ◽  
Targeted Metabolomics ◽  
Serum Samples ◽  
Pilot Studies ◽  
Potential Biomarker ◽  
Receiver Operating Characteristics Curve ◽  
Peritoneal Endometriosis ◽  
Validation Set

ObjectiveTo identify potential serum biomarkers in women with peritoneal endometriosis (PE) by first looking at its source in the peritoneal fluid (PF).DesignCase-control pilot studies, comprising independent discovery and validation sets.SettingKK Women’s and Children’s Hospital, Singapore.Patient(s)Women with laparoscopically confirmed PE and absence of endometriosis (control).Intervention(s)None.Main Outcome Measure(s)In the discovery set, we used untargeted liquid chromatography-mass spectrometry (LC-MS/MS) metabolomics, multivariable and univariable analyses to generate global metabolomic profiles of PF for endometriosis and to identify potential metabolites that could distinguish PE (n=10) from controls (n=31). Using targeted metabolomics, we validated the identified metabolites in PF and sera of cases (n=16 PE) and controls (n=19). We performed the area under the receiver-operating characteristics curve (AUC) analysis to evaluate the diagnostic performance of PE metabolites.Result(s)In the discovery set, PF phosphatidylcholine (34:3) and phenylalanyl-isoleucine were significantly increased in PE than controls groups, with AUC 0.77 (95% confidence interval 0.61-0.92; p=0.018) and AUC 0.98 (0.95-1.02; p<0.001), respectively. In the validation set, phenylalanyl-isoleucine retained discriminatory performance to distinguish PE from controls in both PF (AUC 0.77; 0.61-0.92; p=0.006) and serum samples (AUC 0.81; 0.64-0.99; p=0.004).Conclusion(s)Our preliminary results propose phenylalanyl-isoleucine as a potential biomarker of PE, which may be used as a minimally-invasive diagnostic biomarker of PE.

scholarly journals Predicting bloodstream infection outcome using machine learning

2021 ◽  
Author(s):  
Yazeed Zoabi ◽  
Orli Kehat ◽  
Dan Lahav ◽  
Ahuva Weiss-Meilik ◽  
Amos Adler ◽  
...  
Keyword(s):  
Electronic Medical Records ◽  
Patient Outcomes ◽  
Medical Records ◽  
Bloodstream Infections ◽  
Operating Characteristics ◽  
Is Implementation ◽  
Adverse Health Outcomes ◽  
Receiver Operating Characteristics Curve ◽  
History Of ◽  
Poor Outcomes

Bloodstream infections (BSI) are a main cause of infectious disease morbidity and mortality worldwide. Early prediction of patients at high risk of poor outcomes of BSI is important for earlier decision making and effective patient stratification. We developed electronic medical record-based ma-chine learning models that predict patient outcomes of BSI. The area under the receiver-operating characteristics curve was 0.82 for a full featured inclusive model, and 0.81 for a compact model using only 25 features. Our models were trained, using electronic medical records that include demographics, blood tests, and the medical and diagnosis history of 7,889 hospitalized patients diagnosed with BSI. Among the implications of this work is implementation of the models as a basis for selective rapid microbiological identification, toward earlier administration of appropriate antibiotic therapy. Additionally, our models may help reduce the development of BSI and its associated adverse health outcomes and complications.

scholarly journals Rare, low frequency and common coding variants in CHRNA5 and their contribution to nicotine dependence in European and African Americans

2015 ◽  
Vol 21 (5) ◽  
pp. 601-607 ◽  
Author(s):  
E Olfson ◽  
N L Saccone ◽  
E O Johnson ◽  
L-S Chen ◽  
R Culverhouse ◽  
...  
Keyword(s):  
African Americans ◽  
Nicotine Dependence ◽  
Low Frequency ◽  
Common Coding ◽  
Coding Variants

Standard effluent potassium concentration as a predictive factor for postreperfusion significant arrhythmias in deceased liver transplantation

2021 ◽  
Keyword(s):  
Liver Transplantation ◽  
Odds Ratio ◽  
Serum Potassium Level ◽  
Potassium Concentration ◽  
Multivariable Analysis ◽  
Operating Characteristics ◽  
Receiver Operating Characteristics Curve ◽  
Independent Risk Factors ◽  
Early Allograft Dysfunction

Objectives: Postreperfusion significant arrhythmias (PRSA), which is known as part of the diagnostic criteria for postreperfusion syndrome, may serve as a precursor of postreperfusion cardiac arrest (PRCA). Considering the possible relationship between the use of liver grafts with high effluent potassium (eK+) concentrations and PRCA, we aimed to investigate the role of eK+ in PRSA development in deceased liver transplantation (LT). Methods: Using the prospectively collected data from a prior observational study, a retrospective study of 91 adult LT recipients with eK+ measurements between November 2016 and December 2018 was conducted to determine the incidence, predictors, and outcomes of PRSA. Results: PRSA occurred in 46 cases (50.5%), and PRCA occurred in 8 patients (8.8%). Multivariable analysis demonstrated elevated eK+ concentration before reperfusion (odds ratio [OR], 1.425; 95% confidence interval [CI] 1.134–1.790; P = 0.002), and higher serum potassium level at one minute following reperfusion (sK+1) (OR, 3.244; 95% CI 1.668–6.380; P = 0.001) as independent risk factors for PRSA. An eK+ ≥6.9 mmoL/L could predict PRSA with a sensitivity of 71.7% and a specificity of 80.0% (area under the receiver-operating characteristics curve [AUROC], 0.828). In comparison, an sK+1 ≥5.5 mmoL/L could predict PRSA with a sensitivity of 87.0% and a specificity of 64.4% (AUROC, 0.810). PRSA was associated with increased risks of PRCA, postreperfusion vasoplegia, and postoperative early allograft dysfunction. Conclusions: This study has demonstrated that eK+ has the potential to predict PRSA in deceased LT. These findings need confirmation in further studies.

Modules in Biological Networks

2013 ◽  
pp. 637-663
Author(s):  
Bing Zhang ◽  
Zhiao Shi
Keyword(s):  
Biological Networks ◽  
Protein Complex ◽  
Protein Function ◽  
Protein Function Prediction ◽  
Single Gene ◽  
Biological Systems ◽  
Function Prediction ◽  
Diverse Group ◽  
Biological Studies ◽  
Gene Level

One of the most prominent properties of networks representing complex systems is modularity. Network-based module identification has captured the attention of a diverse group of scientists from various domains and a variety of methods have been developed. The ability to decompose complex biological systems into modules allows the use of modules rather than individual genes as units in biological studies. A modular view is shaping research methods in biology. Module-based approaches have found broad applications in protein complex identification, protein function prediction, protein expression prediction, as well as disease studies. Compared to single gene-level analyses, module-level analyses offer higher robustness and sensitivity. More importantly, module-level analyses can lead to a better understanding of the design and organization of complex biological systems.

Mid-upper arm circumference as a screening tool for identifying adolescents with thinness

2020 ◽  
pp. 1-10
Author(s):  
Binyam Girma Sisay ◽  
Demewoz Haile ◽  
Hamid Yimam Hassen ◽  
Seifu Hagos Gebreyesus
Keyword(s):  
Addis Ababa ◽  
High Sensitivity ◽  
Cross Sectional Study ◽  
Operating Characteristics ◽  
Upper Arm ◽  
Cross Sectional ◽  
Arm Circumference ◽  
Receiver Operating Characteristics Curve ◽  
Adolescence Period ◽  
Mid Upper Arm Circumference

Abstract Objective: To evaluate the performance of mid-upper arm circumference (MUAC) to identify thinness in the late adolescence period (aged 15–19 years) in Ethiopia. Design: We conducted a school-based cross-sectional study. The receiver operating characteristics curve was used to examine the validity of MUAC compared with BMI Z-score to identify adolescents with thinness (BMI Z-score <−2 sd). Settings: Fifteen high schools (grade 9–12) located in Addis Ababa, Ethiopia. Participants: A total of 851 adolescent (456 males and 395 females) were included in the study. Results: The prevalence of thinness and severe thinness among high-school adolescents in Addis Ababa was 9·5 % (95 % CI 7·7, 11·7 %). The overall AUC for MUAC against BMI Z-score <−2 SD was 0·91 (95 % CI 0·88, 0·93). The optimal MUAC cut-offs to identify thinness were 23·3 cm for males and 22·6 cm for females. These cut-off points give high sensitivity and specificity for both males (a sensitivity of 87·9 % and a specificity of 75·9 %) and females (a sensitivity of 100 % and a specificity 88·2 %). Conclusions: MUAC has a comparable level of accuracy with BMI Z-score to identify thinness in adolescents aged 15–19 years. Hence, MUAC could be used as an alternative tool for surveillance and screening of thinness among adolescents aged 15–19 years. The optimum cut-off proposed by this study may incorrectly include a large number of adolescents when used in a relatively well-nourished population. In this situation, it would be necessary to choose a cut-off with greater positive predictive value.

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