scholarly journals Diagnostic AI Modeling and Pseudo Time Series Profiling of AD and PD Based on Individualized Serum Proteome Data

2021 ◽  
Vol 1 ◽  
Author(s):  
Jianhu Zhang ◽  
Xiuli Zhang ◽  
Yuan Sh ◽  
Benliang Liu ◽  
Zhiyuan Hu

Background: Parkinson’s disease (PD), Alzheimer’s disease (AD) are common neurodegenerative disease, while mild cognitive impairment (MCI) may be happened in the early stage of AD or PD. Blood biomarkers are considered to be less invasive, less cost and more convenient, and there is tremendous potential for the diagnosis and prediction of neurodegenerative diseases. As a recently mentioned field, artificial intelligence (AI) is often applied in biology and shows excellent results. In this article, we use AI to model PD, AD, MCI data and analyze the possible connections between them.Method: Human blood protein microarray profiles including 156 CT, 50 MCI, 132 PD, 50 AD samples are collected from Gene Expression Omnibus (GEO). First, we used bioinformatics methods and feature engineering in machine learning to screen important features, constructed artificial neural network (ANN) classifier models based on these features to distinguish samples, and evaluated the model’s performance with classification accuracy and Area Under Curve (AUC). Second, we used Ingenuity Pathway Analysis (IPA) methods to analyse the pathways and functions in early stage and late stage samples of different diseases, and potential targets for drug intervention by predicting upstream regulators.Result: We used different classifier to construct the model and finally found that ANN model would outperform the traditional machine learning model. In summary, three different classifiers were constructed to be used in different application scenarios, First, we incorporated 6 indicators, including EPHA2, MRPL19, SGK2, to build a diagnostic model for AD with a test set accuracy of up to 98.07%. Secondly, incorporated 15 indicators such as ERO1LB, FAM73B, IL1RN to build a diagnostic model for PD, with a test set accuracy of 97.05%. Then, 15 indicators such as XG, FGFR3 and CDC37 were incorporated to establish a four-category diagnostic model for both AD and PD, with a test set accuracy of 98.71%. All classifier models have an auc value greater than 0.95. Then, we verified that the constructed feature engineering filtered out fewer important features but contained more information, which helped to build a better model. In addition, by classifying the disease types more carefully into early and late stages of AD, MCI, and PD, respectively, we found that early PD may occur earlier than early MCI. Finally, there are 24 proteins that are both differentially expressed proteins and upstream regulators in the disease group versus the normal group, and these proteins may serve as potential therapeutic targets and targets for subsequent studies.Conclusion: The feature engineering we build allows better extraction of information while reducing the number of features, which may help in subsequent applications. Building a classifier based on blood protein profiles using deep learning methods can achieve better classification performance, and it can help us to diagnose the disease early. Overall, it is important for us to study neurodegenerative diseases from both diagnostic and interventional aspects.

2021 ◽  
Author(s):  
Jianhu Zhang ◽  
Xiuli zhang ◽  
Yuan Sh ◽  
Benliang Liu ◽  
Zhiyuan Hu

Abstract BackgroundParkinson's disease (PD), Alzhaimer's disease (AD) are common neurodegenerative disease, and mild cognitive impairment (MCI) may be happened in the early stage of AD or PD. Blood biomarkers are considered to be less invasive, less cost and more convenient, and there is tremendous potentia for the diagnosis and prediction of neurodegenerative diseases. As a recently mentioned field, artificial intelligence (AI) is often applyed in biology and shows excellent results.MethodHuman blood protein microarray profiles including 156 CT, 50 MCI, 132 PD, 50 AD samples are collected from Gene Expression Omnibus (GEO). First, we used bioinformatics methods and feature engineering in machine learning to screen important features, constructed ANNclassifier models based on these features to distinguish samples, and evaluated the model's performance with classification accuracy and Area Under Curve (AUC). Secenod, we used Ingenuity Pathway Anaylsis (IPA) methods to analyse the pathways and functions in early stage and late stage samples of different diseases, and potential targets for drug intervention by predicting upstream regulators.ResultOverall, we incorporated six indicators, including EPHA2, MRPL19, SGK2, to build a diagnostic model for AD with a test set accuracy of up to 98.07%. Incorporating 15 indicators such as ERO1LB, FAM73B, IL1RN to build a diagnostic model for PD, with a test set accuracy of 97.05%. Thirty indicators such as XG, FGFR3 and CDC37 were incorporated to establish a four-category diagnostic model for both AD and PD, with a test set accuracy of 98.71%. In addition,we found that early PD may occur earlier than early MCI. Finally, there are 24 proteins that may serve as potential therapeutic targetsConclusionUsing deep learning methods to build classifiers based on blood protein profile can achieve better classification performance, and it helps us to diagnose the disease early. In total, it is important for us to study neurodegenerative diseases from both diagnostic and interventional aspects.


2021 ◽  
Vol 13 ◽  
Author(s):  
Yuan Sh ◽  
Benliang Liu ◽  
Jianhu Zhang ◽  
Ying Zhou ◽  
Zhiyuan Hu ◽  
...  

Background: There are no obvious clinical signs and symptoms in the early stages of Alzheimer’s disease (AD), and most patients usually have mild cognitive impairment (MCI) before diagnosis. Therefore, early diagnosis of AD is very critical. This paper mainly discusses the blood biomarkers of AD patients and uses machine learning methods to study the changes of blood transcriptome during the development of AD and to search for potential blood biomarkers for AD.Methods: Individualized blood mRNA expression data of 711 patients were downloaded from the GEO database, including the control group (CON) (238 patients), MCI (189 patients), and AD (284 patients). Firstly, we analyzed the subcellular localization, protein types and enrichment pathways of the differentially expressed mRNAs in each group, and established an artificial intelligence individualized diagnostic model. Furthermore, the XCell tool was used to analyze the blood mRNA expression data and obtain blood cell composition and quantitative data. Ratio characteristics were established for mRNA and XCell data. Feature engineering operations such as collinearity and importance analysis were performed on all features to obtain the best feature solicitation. Finally, four machine learning algorithms, including linear support vector machine (SVM), Adaboost, random forest and artificial neural network, were used to model the optimal feature combinations and evaluate their classification performance in the test set.Results: Through feature engineering screening, the best feature collection was obtained. Moreover, the artificial intelligence individualized diagnosis model established based on this method achieved a classification accuracy of 91.59% in the test set. The area under curve (AUC) of CON, MCI, and AD were 0.9746, 0.9536, and 0.9807, respectively.Conclusion: The results of cell homeostasis analysis suggested that the homeostasis of Natural killer T cell (NKT) might be related to AD, and the homeostasis of Granulocyte macrophage progenitor (GMP) might be one of the reasons for AD.


Materials ◽  
2021 ◽  
Vol 14 (4) ◽  
pp. 713
Author(s):  
Zhi Wan ◽  
Yading Xu ◽  
Branko Šavija

Compressive strength is the most significant metric to evaluate the mechanical properties of concrete. Machine Learning (ML) methods have shown promising results for predicting compressive strength of concrete. However, at present, no in-depth studies have been devoted to the influence of dimensionality reduction on the performance of different ML models for this application. In this work, four representative ML models, i.e., Linear Regression (LR), Support Vector Regression (SVR), Extreme Gradient Boosting (XGBoost), and Artificial Neural Network (ANN), are trained and used to predict the compressive strength of concrete based on its mixture composition and curing age. For each ML model, three kinds of features are used as input: the eight original features, six Principal Component Analysis (PCA)-selected features, and six manually selected features. The performance as well as the training speed of those four ML models with three different kinds of features is assessed and compared. Based on the obtained results, it is possible to make a relatively accurate prediction of concrete compressive strength using SVR, XGBoost, and ANN with an R-square of over 0.9. When using different features, the highest R-square of the test set occurs in the XGBoost model with manually selected features as inputs (R-square = 0.9339). The prediction accuracy of the SVR model with manually selected features (R-square = 0.9080) or PCA-selected features (R-square = 0.9134) is better than the model with original features (R-square = 0.9003) without dramatic running time change, indicating that dimensionality reduction has a positive influence on SVR model. For XGBoost, the model with PCA-selected features shows poorer performance (R-square = 0.8787) than XGBoost model with original features or manually selected features. A possible reason for this is that the PCA-selected features are not as distinguishable as the manually selected features in this study. In addition, the running time of XGBoost model with PCA-selected features is longer than XGBoost model with original features or manually selected features. In other words, dimensionality reduction by PCA seems to have an adverse effect both on the performance and the running time of XGBoost model. Dimensionality reduction has an adverse effect on the performance of LR model and ANN model because the R-squares on test set of those two models with manually selected features or PCA-selected features are lower than models with original features. Although the running time of ANN is much longer than the other three ML models (less than 1s) in three scenarios, dimensionality reduction has an obviously positive influence on running time without losing much prediction accuracy for ANN model.


2021 ◽  
Author(s):  
Yuan Sh ◽  
Benliang Liu ◽  
Jianhu Zhang ◽  
Ying Zhou ◽  
Zhiyuan Hu ◽  
...  

Abstract BackgroundThere are no obvious clinical symptoms in the early stages of Alzheimer's disease (AD). Therefore, the diagnosis of AD directly leads to serious lag. Studies have shown that most patients usually have mild cognitive impairment (MCI) before diagnosis. Therefore, the actual time of diagnosis of AD is much later than the time of onset. This brings great difficulties to the late treatment and management of patients. Therefore, early diagnosis of AD is very important. This paper mainly discusses the blood biomarkers of AD patients and uses machine learning methods to find the changes of blood transcriptome during the development of AD, and to search for potential blood biomarkers.MethodIndividualized blood mRNA expression data were downloaded from the GEO database in 711 patients, including control group (CON) (238 patients), MCI (189 patients), and AD (284 patients). Firstly, we analyzed the subcellular localization, protein types and enrichment pathways of the differentially expressed mRNAs in each group, and established an artificial intelligence individualized diagnostic model. Furthermore, Xcell tool was used to analyze the blood mRNA expression data to obtain the composition and quantitative data of blood cells. Ratio characteristics were established for mRNA and Xcell data respectively. Feature engineering operations such as collinearity and importance analysis are performed on all features to obtain the best feature solicitation. Finally, four machine learning algorithms, including linear support vector machine (SVM), Adaboost, random forest and artificial neural network, were used to model the optimal feature combinations and evaluate their classification performance in the test set.ResultA total of 5625 differential mRNAs were obtained by differential analysis of blood mRNAs. Through feature engineering screening, the best feature collection was obtained, and the artificial intelligence individualized diagnosis model established based on this method achieved a classification accuracy of 91.59% in the test set. The AUC of CON, MCI and AD were 0.9746, 0.9536 and 0.9807, respectively. ConclusionThe 181 features are composed of four dimensions, which can accurately classify CON, MCI and AD groups, suggesting that machine learning methods can capture changes in blood biomarkers in Alzheimer's patients. The results of cell homeostasis analysis suggested that the homeostasis of NTK cells might be related to AD, and the homeostasis of GMP might be one of the reasons for AD.


2018 ◽  
Vol 1 (1) ◽  
pp. 236-247
Author(s):  
Divya Srivastava ◽  
Rajitha B. ◽  
Suneeta Agarwal

Diseases in leaves can cause the significant reduction in both quality and quantity of agricultural production. If early and accurate detection of disease/diseases in leaves can be automated, then the proper remedy can be taken timely. A simple and computationally efficient approach is presented in this paper for disease/diseases detection on leaves. Only detecting the disease is not beneficial without knowing the stage of disease thus the paper also determine the stage of disease/diseases by quantizing the affected of the leaves by using digital image processing and machine learning. Though there exists a variety of diseases on leaves, but the bacterial and fungal spots (Early Scorch, Late Scorch, and Leaf Spot) are the most prominent diseases found on leaves. Keeping this in mind the paper deals with the detection of Bacterial Blight and Fungal Spot both at an early stage (Early Scorch) and late stage (Late Scorch) on the variety of leaves. The proposed approach is divided into two phases, in the first phase, it identifies one or more disease/diseases existing on leaves. In the second phase, amount of area affected by the disease/diseases is calculated. The experimental results obtained showed 97% accuracy using the proposed approach.


2020 ◽  
Vol 16 (8) ◽  
pp. 1088-1105
Author(s):  
Nafiseh Vahedi ◽  
Majid Mohammadhosseini ◽  
Mehdi Nekoei

Background: The poly(ADP-ribose) polymerases (PARP) is a nuclear enzyme superfamily present in eukaryotes. Methods: In the present report, some efficient linear and non-linear methods including multiple linear regression (MLR), support vector machine (SVM) and artificial neural networks (ANN) were successfully used to develop and establish quantitative structure-activity relationship (QSAR) models capable of predicting pEC50 values of tetrahydropyridopyridazinone derivatives as effective PARP inhibitors. Principal component analysis (PCA) was used to a rational division of the whole data set and selection of the training and test sets. A genetic algorithm (GA) variable selection method was employed to select the optimal subset of descriptors that have the most significant contributions to the overall inhibitory activity from the large pool of calculated descriptors. Results: The accuracy and predictability of the proposed models were further confirmed using crossvalidation, validation through an external test set and Y-randomization (chance correlations) approaches. Moreover, an exhaustive statistical comparison was performed on the outputs of the proposed models. The results revealed that non-linear modeling approaches, including SVM and ANN could provide much more prediction capabilities. Conclusion: Among the constructed models and in terms of root mean square error of predictions (RMSEP), cross-validation coefficients (Q2 LOO and Q2 LGO), as well as R2 and F-statistical value for the training set, the predictive power of the GA-SVM approach was better. However, compared with MLR and SVM, the statistical parameters for the test set were more proper using the GA-ANN model.


2020 ◽  
Vol 15 ◽  
Author(s):  
Elham Shamsara ◽  
Sara Saffar Soflaei ◽  
Mohammad Tajfard ◽  
Ivan Yamshchikov ◽  
Habibollah Esmaili ◽  
...  

Background: Coronary artery disease (CAD) is an important cause of mortality and morbidity globally. Objective : The early prediction of the CAD would be valuable in identifying individuals at risk, and in focusing resources on its prevention. In this paper, we aimed to establish a diagnostic model to predict CAD by using three approaches of ANN (pattern recognition-ANN, LVQ-ANN, and competitive ANN). Methods: One promising method for early prediction of disease based on risk factors is machine learning. Among different machine learning algorithms, the artificial neural network (ANN) algo-rithms have been applied widely in medicine and a variety of real-world classifications. ANN is a non-linear computational model, that is inspired by the human brain to analyze and process complex datasets. Results: Different methods of ANN that are investigated in this paper indicates in both pattern recognition ANN and LVQ-ANN methods, the predictions of Angiography+ class have high accuracy. Moreover, in CNN the correlations between the individuals in cluster ”c” with the class of Angiography+ is strongly high. This accuracy indicates the significant difference among some of the input features in Angiography+ class and the other two output classes. A comparison among the chosen weights in these three methods in separating control class and Angiography+ shows that hs-CRP, FSG, and WBC are the most substantial excitatory weights in recognizing the Angiography+ individuals although, HDL-C and MCH are determined as inhibitory weights. Furthermore, the effect of decomposition of a multi-class problem to a set of binary classes and random sampling on the accuracy of the diagnostic model is investigated. Conclusion : This study confirms that pattern recognition-ANN had the most accuracy of performance among different methods of ANN. That’s due to the back-propagation procedure of the process in which the network classify input variables based on labeled classes. The results of binarization show that decomposition of the multi-class set to binary sets could achieve higher accuracy.


Author(s):  
Shu-Farn Tey ◽  
Chung-Feng Liu ◽  
Tsair-Wei Chien ◽  
Chin-Wei Hsu ◽  
Kun-Chen Chan ◽  
...  

Unplanned patient readmission (UPRA) is frequent and costly in healthcare settings. No indicators during hospitalization have been suggested to clinicians as useful for identifying patients at high risk of UPRA. This study aimed to create a prediction model for the early detection of 14-day UPRA of patients with pneumonia. We downloaded the data of patients with pneumonia as the primary disease (e.g., ICD-10:J12*-J18*) at three hospitals in Taiwan from 2016 to 2018. A total of 21,892 cases (1208 (6%) for UPRA) were collected. Two models, namely, artificial neural network (ANN) and convolutional neural network (CNN), were compared using the training (n = 15,324; ≅70%) and test (n = 6568; ≅30%) sets to verify the model accuracy. An app was developed for the prediction and classification of UPRA. We observed that (i) the 17 feature variables extracted in this study yielded a high area under the receiver operating characteristic curve of 0.75 using the ANN model and that (ii) the ANN exhibited better AUC (0.73) than the CNN (0.50), and (iii) a ready and available app for predicting UHA was developed. The app could help clinicians predict UPRA of patients with pneumonia at an early stage and enable them to formulate preparedness plans near or after patient discharge from hospitalization.


Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 913
Author(s):  
Johannes Fahrmann ◽  
Ehsan Irajizad ◽  
Makoto Kobayashi ◽  
Jody Vykoukal ◽  
Jennifer Dennison ◽  
...  

MYC is an oncogenic driver in the pathogenesis of ovarian cancer. We previously demonstrated that MYC regulates polyamine metabolism in triple-negative breast cancer (TNBC) and that a plasma polyamine signature is associated with TNBC development and progression. We hypothesized that a similar plasma polyamine signature may associate with ovarian cancer (OvCa) development. Using mass spectrometry, four polyamines were quantified in plasma from 116 OvCa cases and 143 controls (71 healthy controls + 72 subjects with benign pelvic masses) (Test Set). Findings were validated in an independent plasma set from 61 early-stage OvCa cases and 71 healthy controls (Validation Set). Complementarity of polyamines with CA125 was also evaluated. Receiver operating characteristic area under the curve (AUC) of individual polyamines for distinguishing cases from healthy controls ranged from 0.74–0.88. A polyamine signature consisting of diacetylspermine + N-(3-acetamidopropyl)pyrrolidin-2-one in combination with CA125 developed in the Test Set yielded improvement in sensitivity at >99% specificity relative to CA125 alone (73.7% vs 62.2%; McNemar exact test 2-sided P: 0.019) in the validation set and captured 30.4% of cases that were missed with CA125 alone. Our findings reveal a MYC-driven plasma polyamine signature associated with OvCa that complemented CA125 in detecting early-stage ovarian cancer.


Sign in / Sign up

Export Citation Format

Share Document