scholarly journals Predicting Pathogenicity of Missense Variants with Weakly Supervised Regression

2019 ◽  
Author(s):  
Yue Cao ◽  
Yuanfei Sun ◽  
Mostafa Karimi ◽  
Haoran Chen ◽  
Oluwaseyi Moronfoye ◽  
...  
Keyword(s):  
Clinical Significance ◽  
Metal Binding ◽  
Molecular Mechanisms ◽  
Operating Characteristic ◽  
Characteristic Curve ◽  
Critical Assessment ◽  
Model Interpretation ◽  
Genome Interpretation ◽  
Variation Data ◽  
Weakly Supervised

Quickly growing genetic variation data of unknown clinical significance demand computational methods that can reliably predict clinical phenotypes and deeply unravel molecular mechanisms. On the platform enabled by CAGI (Critical Assessment of Genome Interpretation), we develop a novel “weakly supervised” regression (WSR) model that not only predicts precise clinical significance (probability of pathogenicity) from inexact training annotations (class of pathogenicity) but also infers underlying molecular mechanisms in a variant-specific fashion. Compared to multi-class logistic regression, a representative multi-class classifier, our kernelized WSR improves the performance for the ENIGMA Challenge set from 0.72 to 0.97 in binary AUC (Area Under the receiver operating characteristic Curve) and from 0.64 to 0.80 in ordinal multi-class AUC. WSR model interpretation and protein structural interpretation reach consensus in corroborating the most probable molecular mechanisms by which some pathogenic BRCA1 variants confer clinical significance, namely metal-binding disruption for C44F and C47Y, protein-binding disruption for M18T, and structure destabilization for S1715N.

Predicting the interaction biomolecule types for lncRNA: an ensemble deep learning approach

2020 ◽  
Author(s):  
Yu Zhang ◽  
Cangzhi Jia ◽  
Chee Keong Kwoh
Keyword(s):  
Deep Learning ◽  
Molecular Mechanisms ◽  
Operating Characteristic ◽  
Cross Validation ◽  
Characteristic Curve ◽  
Published Data ◽  
Different Types ◽  
Precision Recall Curve ◽  
Deep Learning Model ◽  
Fold Cross Validation

Abstract Long noncoding RNAs (lncRNAs) play significant roles in various physiological and pathological processes via their interactions with biomolecules like DNA, RNA and protein. The existing in silico methods used for predicting the functions of lncRNA mainly rely on calculating the similarity of lncRNA or investigating whether an lncRNA can interact with a specific biomolecule or disease. In this work, we explored the functions of lncRNA from a different perspective: we presented a tool for predicting the interaction biomolecule type for a given lncRNA. For this purpose, we first investigated the main molecular mechanisms of the interactions of lncRNA–RNA, lncRNA–protein and lncRNA–DNA. Then, we developed an ensemble deep learning model: lncIBTP (lncRNA Interaction Biomolecule Type Prediction). This model predicted the interactions between lncRNA and different types of biomolecules. On the 5-fold cross-validation, the lncIBTP achieves average values of 0.7042 in accuracy, 0.7903 and 0.6421 in macro-average area under receiver operating characteristic curve and precision–recall curve, respectively, which illustrates the model effectiveness. Besides, based on the analysis of the collected published data and prediction results, we hypothesized that the characteristics of lncRNAs that interacted with DNA may be different from those that interacted with only RNA.

scholarly journals Weakly-supervised deep learning for ultrasound diagnosis of breast cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jaeil Kim ◽  
Hye Jung Kim ◽  
Chanho Kim ◽  
Jin Hwa Lee ◽  
Keum Won Kim ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Deep Learning ◽  
Operating Characteristic ◽  
Image Annotation ◽  
Characteristic Curve ◽  
External Validation ◽  
Region Of Interest ◽  
Internal Validation ◽  
Breast Masses ◽  
Weakly Supervised

AbstractConventional deep learning (DL) algorithm requires full supervision of annotating the region of interest (ROI) that is laborious and often biased. We aimed to develop a weakly-supervised DL algorithm that diagnosis breast cancer at ultrasound without image annotation. Weakly-supervised DL algorithms were implemented with three networks (VGG16, ResNet34, and GoogLeNet) and trained using 1000 unannotated US images (500 benign and 500 malignant masses). Two sets of 200 images (100 benign and 100 malignant masses) were used for internal and external validation sets. For comparison with fully-supervised algorithms, ROI annotation was performed manually and automatically. Diagnostic performances were calculated as the area under the receiver operating characteristic curve (AUC). Using the class activation map, we determined how accurately the weakly-supervised DL algorithms localized the breast masses. For internal validation sets, the weakly-supervised DL algorithms achieved excellent diagnostic performances, with AUC values of 0.92–0.96, which were not statistically different (all Ps > 0.05) from those of fully-supervised DL algorithms with either manual or automated ROI annotation (AUC, 0.92–0.96). For external validation sets, the weakly-supervised DL algorithms achieved AUC values of 0.86–0.90, which were not statistically different (Ps > 0.05) or higher (P = 0.04, VGG16 with automated ROI annotation) from those of fully-supervised DL algorithms (AUC, 0.84–0.92). In internal and external validation sets, weakly-supervised algorithms could localize 100% of malignant masses, except for ResNet34 (98%). The weakly-supervised DL algorithms developed in the present study were feasible for US diagnosis of breast cancer with well-performing localization and differential diagnosis.

scholarly journals Clinical Value and Underlying Mechanisms of Upregulated LINC00485 in Hepatocellular Carcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Xinyu Zhu ◽  
Yanlin Feng ◽  
Dingdong He ◽  
Zi Wang ◽  
Fangfang Huang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Molecular Mechanisms ◽  
Operating Characteristic ◽  
Characteristic Curve ◽  
Underlying Mechanism ◽  
Clinical Value ◽  
Serum Samples ◽  
Underlying Mechanisms ◽  
Insight Into

AimsThis study aimed to reveal the functional role of LINC00485 in hepatocellular carcinoma (HCC).Materials & Methods210 serum samples from Zhongnan Hospital of Wuhan University were employed to evaluate clinical value of LINC00485. Bioinformatics analysis was adopted to explore its potential mechanisms.ResultsLINC00485 was confirmed to be upregulated in HCC tissues and serum samples. Survival analysis and receiver operating characteristic curve revealed its prognostic and diagnostic roles. The combination of serum LINC00485 with AFP can remarkably improve diagnostic ability of HCC. Exploration of the underlying mechanism demonstrated that LINC00485 might exert pro-oncogenic activity by LINC00485—three miRNAs—four mRNAs network.ConclusionsOur study unveiled that upregulated LINC00485 could act as a potential diagnostic and prognostic biomarker and provide a novel insight into the molecular mechanisms of LINC00485 in HCC pathogenesis.

Serum miR-21 and miR-26a Levels Negatively Correlate with Severity of Cirrhosis in Patients with Chronic Hepatitis B

MicroRNA ◽  
2018 ◽  
Vol 8 (1) ◽  
pp. 86-92 ◽  
Author(s):  
Shili Jiang ◽  
Wei Jiang ◽  
Ying Xu ◽  
Xiaoning Wang ◽  
Yongping Mu ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis B ◽  
Chronic Hepatitis B ◽  
Operating Characteristic ◽  
Characteristic Curve ◽  
Curve Analysis ◽  
Pugh Class ◽  
Operating Characteristic Curve ◽  
Class C ◽  
Circulating Levels

Background and Objective: Accurately evaluating the severity of liver cirrhosis is essential for clinical decision making and disease management. This study aimed to evaluate the value of circulating levels of microRNA (miR)-26a and miR-21 as novel noninvasive biomarkers in detecting severity of cirrhosis in patients with chronic hepatitis B. </P><P> Methods: Thirty patients with clinically diagnosed chronic hepatitis B-related cirrhosis and 30 healthy individuals were selected. The serum levels of miR-26a and miR-21 were quantified by qRT-PCR. Receiver operating characteristic curve analysis was performed to evaluate the sensitivity and specificity of the miRNAs for detecting the severity of cirrhosis. Results: Serum miR-26a and miR-21 levels were found to be significantly downregulated in patients with severe cirrhosis scored at Child-Pugh class C in comparison to healthy controls (miR-26a p<0.01, and miR-21 p<0.001, respectively). The circulating miR-26a and miR-21 levels in patients were positively correlated with serum albumin concentration but negatively correlated with serum total bilirubin concentration and prothrombin time. Receiver operating characteristic curve analysis revealed that both serum miR-26a and miR-21 levels were associated with a high diagnostic accuracy for patients with cirrhosis scored at Child-Pugh class C (miR-26a Cut-off fold change at ≤0.4, Sensitivity: 84.62%, Specificity: 89.36%, P<0.0001; miR-21 Cut-off fold change at ≤0.6, Sensitivity: 84.62%, Specificity: 78.72%, P<0.0001). Our results indicate that the circulating levels of miR-26a and miR-21 are closely related to the extent of liver decompensation, and the decreased levels are capable of discriminating patients with cirrhosis at Child-Pugh class C from the whole cirrhosis cases.

A validated novel preoperative index to predict the extent of intraperitoneal contamination in patients with acute abdominal pathology: A cohort study

2019 ◽  
Vol 30 (7-8) ◽  
pp. 221-228
Author(s):  
Shahab Hajibandeh ◽  
Shahin Hajibandeh ◽  
Nicholas Hobbs ◽  
Jigar Shah ◽  
Matthew Harris ◽  
...  
Keyword(s):  
Receiver Operating Characteristic Curve ◽  
Receiver Operating Characteristic ◽  
Operating Characteristic ◽  
Validation Cohort ◽  
Characteristic Curve ◽  
Curve Analysis ◽  
Emergency Laparotomy ◽  
Contamination Index ◽  
Operating Characteristic Curve ◽  
Receiver Operating

Aims To investigate whether an intraperitoneal contamination index (ICI) derived from combined preoperative levels of C-reactive protein, lactate, neutrophils, lymphocytes and albumin could predict the extent of intraperitoneal contamination in patients with acute abdominal pathology. Methods Patients aged over 18 who underwent emergency laparotomy for acute abdominal pathology between January 2014 and October 2018 were randomly divided into primary and validation cohorts. The proposed intraperitoneal contamination index was calculated for each patient in each cohort. Receiver operating characteristic curve analysis was performed to determine discrimination of the index and cut-off values of preoperative intraperitoneal contamination index that could predict the extent of intraperitoneal contamination. Results Overall, 468 patients were included in this study; 234 in the primary cohort and 234 in the validation cohort. The analyses identified intraperitoneal contamination index of 24.77 and 24.32 as cut-off values for purulent contamination in the primary cohort (area under the curve (AUC): 0.73, P < 0.0001; sensitivity: 84%, specificity: 60%) and validation cohort (AUC: 0.83, P < 0.0001; sensitivity: 91%, specificity: 69%), respectively. Receiver operating characteristic curve analysis also identified intraperitoneal contamination index of 33.70 and 33.41 as cut-off values for feculent contamination in the primary cohort (AUC: 0.78, P < 0.0001; sensitivity: 87%, specificity: 64%) and validation cohort (AUC: 0.79, P < 0.0001; sensitivity: 86%, specificity: 73%), respectively. Conclusions As a predictive measure which is derived purely from biomarkers, intraperitoneal contamination index may be accurate enough to predict the extent of intraperitoneal contamination in patients with acute abdominal pathology and to facilitate decision-making together with clinical and radiological findings.

scholarly journals MicroRNAs-1299, -126-3p and -30e-3p as Potential Diagnostic Biomarkers for Prediabetes

Diagnostics ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 949
Author(s):  
Cecil J. Weale ◽  
Don M. Matshazi ◽  
Saarah F. G. Davids ◽  
Shanel Raghubeer ◽  
Rajiv T. Erasmus ◽  
...  
Keyword(s):  
Receiver Operating Characteristic ◽  
Operating Characteristic ◽  
Characteristic Curve ◽  
Predictive Ability ◽  
Roc Curves ◽  
Tolerance Test ◽  
Cross Sectional Study ◽  
Oral Glucose ◽  
Cross Sectional ◽  
Receiver Operating

This cross-sectional study investigated the association of miR-1299, -126-3p and -30e-3p with and their diagnostic capability for dysglycaemia in 1273 (men, n = 345) South Africans, aged >20 years. Glycaemic status was assessed by oral glucose tolerance test (OGTT). Whole blood microRNA (miRNA) expressions were assessed using TaqMan-based reverse transcription quantitative-PCR (RT-qPCR). Receiver operating characteristic (ROC) curves assessed the ability of each miRNA to discriminate dysglycaemia, while multivariable logistic regression analyses linked expression with dysglycaemia. In all, 207 (16.2%) and 94 (7.4%) participants had prediabetes and type 2 diabetes mellitus (T2DM), respectively. All three miRNAs were significantly highly expressed in individuals with prediabetes compared to normotolerant patients, p < 0.001. miR-30e-3p and miR-126-3p were also significantly more expressed in T2DM versus normotolerant patients, p < 0.001. In multivariable logistic regressions, the three miRNAs were consistently and continuously associated with prediabetes, while only miR-126-3p was associated with T2DM. The ROC analysis indicated all three miRNAs had a significant overall predictive ability to diagnose prediabetes, diabetes and the combination of both (dysglycaemia), with the area under the receiver operating characteristic curve (AUC) being significantly higher for miR-126-3p in prediabetes. For prediabetes diagnosis, miR-126-3p (AUC = 0.760) outperformed HbA1c (AUC = 0.695), p = 0.042. These results suggest that miR-1299, -126-3p and -30e-3p are associated with prediabetes, and measuring miR-126-3p could potentially contribute to diabetes risk screening strategies.

scholarly journals Concurrent validity of the short version of Montreal Cognitive Assessment (MoCA) for patients with stroke

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yali Feng ◽  
Jiaqi Zhang ◽  
Yi Zhou ◽  
Bo Chen ◽  
Ying Yin
Keyword(s):  
Neurological Disorders ◽  
Cognitive Assessment ◽  
Concurrent Validity ◽  
Operating Characteristic ◽  
Cognitive Impairments ◽  
Characteristic Curve ◽  
Cognitive Status ◽  
Montreal Cognitive Assessment ◽  
Short Version ◽  
External Criterion

AbstractThe aim of the present study was to examine the concurrent validity of 2 Chinese versions of the short version of the Montreal Cognitive Assessment (MoCA) in patients with stroke, i.e., MoCA 5-minute protocol and National Institute for Neurological Disorders and Stroke and Canadian Stroke Network (NINDS-CSN) 5-minute Protocol. A total of 54 patients and 27 healthy controls were enrolled in this study. In this study, the Neurobehavioural Cognitive Status Examination (NCSE) was used as an external criterion of cognitive impairment. We found that the 5-min protocol did not differ from the MoCA in differentiating patients with cognitive impairments from those without (area under the receiver operating characteristic curve, AUC, of 0.948 for the MoCA 5-min protocol v.s. 0.984 for MoCA, P = 0.097). These three assessments demonstrated equal performance in differentiating patients with stroke from controls. The Chinese version of the MoCA 5-min protocol can be used as a valid screening for patients with stroke.

Three plasma-based microRNAs as potent diagnostic biomarkers for endometrial cancer

2021 ◽  
pp. 1-12
Author(s):  
Xingchen Fan ◽  
Minmin Cao ◽  
Cheng Liu ◽  
Cheng Zhang ◽  
Chunyu Li ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Operating Characteristic ◽  
Characteristic Curve ◽  
External Validation ◽  
Diagnostic Value ◽  
Diagnostic Biomarkers ◽  
Non Invasive ◽  
Polymerase Chain ◽  
Public Datasets ◽  
Plasma Mirnas

BACKGROUND: MicroRNAs (miRNAs), with noticeable stability and unique expression pattern in plasma of patients with various diseases, are powerful non-invasive biomarkers for cancer detection including endometrial cancer (EC). OBJECTIVE: The objective of this study was to identify promising miRNA biomarkers in plasma to assist the clinical screening of EC. METHODS: A total of 93 EC and 79 normal control (NC) plasma samples were analyzed using Quantitative Real-time Polymerase Chain Reaction (qRT-PCR) in this four-stage experiment. The receiver operating characteristic curve (ROC) analysis was conducted to evaluate the diagnostic value. Additionally, the expression features of the identified miRNAs were further explored in tissues and plasma exosomes samples. RESULTS: The expression of miR-142-3p, miR-146a-5p, and miR-151a-5p was significantly overexpressed in the plasma of EC patients compared with NCs. Areas under the ROC curve of the 3-miRNA signature were 0.729, 0.751, and 0.789 for the training, testing, and external validation phases, respectively. The diagnostic performance of the identified signature proved to be stable in the three public datasets and superior to the other miRNA biomarkers in EC diagnosis. Moreover, the expression of miR-151a-5p was significantly elevated in EC plasma exosomes. CONCLUSIONS: A signature consisting of 3 plasma miRNAs was identified and showed potential for the non-invasive diagnosis of EC.

scholarly journals Quantitative Assessment of the Echogenicity of a Breast Tumor Predicts the Response to Neoadjuvant Chemotherapy

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3546
Author(s):  
Katarzyna Sylwia Dobruch-Sobczak ◽  
Hanna Piotrzkowska-Wróblewska ◽  
Piotr Karwat ◽  
Ziemowit Klimonda ◽  
Ewa Markiewicz-Grodzicka ◽  
...  
Keyword(s):  
Neoadjuvant Chemotherapy ◽  
Treatment Response ◽  
Roc Analysis ◽  
Operating Characteristic ◽  
Characteristic Curve ◽  
Quantitative Measure ◽  
Malignant Cell ◽  
Breast Cancer Patients ◽  
The Third ◽  
Leibler Divergence

The aim of the study was to improve monitoring the treatment response in breast cancer patients undergoing neoadjuvant chemotherapy (NAC). The IRB approved this prospective study. Ultrasound examinations were performed prior to treatment and 7 days after four consecutive NAC cycles. Residual malignant cell (RMC) measurement at surgery was the standard of reference. Alteration in B-mode ultrasound (tumor echogenicity and volume) and the Kullback-Leibler divergence (kld), as a quantitative measure of amplitude difference, were used. Correlations of these parameters with RMC were assessed and Receiver Operating Characteristic curve (ROC) analysis was performed. Thirty-nine patients (mean age 57 y.) with 50 tumors were included. There was a significant correlation between RMC and changes in quantitative parameters (KLD) after the second, third and fourth course of NAC, and alteration in echogenicity after the third and fourth course. Multivariate analysis of the echogenicity and KLD after the third NAC course revealed a sensitivity of 91%, specificity of 92%, PPV = 77%, NPV = 97%, accuracy = 91%, and AUC of 0.92 for non-responding tumors (RMC ≥ 70%). In conclusion, monitoring the echogenicity and KLD parameters made it possible to accurately predict the treatment response from the second course of NAC.

Sign in / Sign up

Export Citation Format

Share Document