scholarly journals Identifying Drug Targets in Pancreatic Ductal Adenocarcinoma Through Machine Learning, Analyzing Biomolecular Networks, and Structural Modeling

2020 ◽  
Vol 11 ◽  
Author(s):  
Wenying Yan ◽  
Xingyi Liu ◽  
Yibo Wang ◽  
Shuqing Han ◽  
Fan Wang ◽  
...  
Keyword(s):  
Machine Learning ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Drug Targets ◽  
Structural Modeling ◽  
Ductal Adenocarcinoma ◽  
Biomolecular Networks

scholarly journals PDAC-ANN: an artificial neural network to predict Pancreatic Ductal Adenocarcinoma based on gene expression

2019 ◽  
Author(s):  
Palloma Porto Almeida ◽  
Cristina Padre Cardoso ◽  
Leandro Martins de Freitas
Keyword(s):  
Neural Network ◽  
Gene Expression ◽  
Artificial Neural Network ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Drug Targets ◽  
Meta Analysis ◽  
Human Protein ◽  
Ductal Adenocarcinoma ◽  
Human Protein Atlas ◽  
Artificial Neural

AbstractBackgroundAlthough the pancreatic ductal adenocarcinoma (PDAC) presents high mortality and metastatic potential, there is a lack of effective therapies and a low survival rate for this disease. This PDAC scenario urges new strategies for diagnosis, drug targets, and treatment.MethodsWe performed a gene expression microarray meta-analysis of the tumor against healthy tissues in order to identify differentially expressed genes shared among all datasets, named core-genes (CG). We confirmed the pancreatic expressed proteins of the CG through The Human Protein Atlas. The five most expressed proteins in the tumor group were selected to train an artificial neural network to classify samples.ResultsThis microarray included 110 tumor and 77 healthy samples. We identified a CG composed of 60 genes, 58 upregulated and two downregulated. The upregulated CG included proteins and extracellular matrix receptors linked to actin cytoskeleton reorganization. With the Human Protein Atlas, we verified that thirteen genes of the CG are translated, with high or medium expression in most of the pancreatic tumor samples. To train our artificial neural network, we used the five most expressed genes (KRT19, LAMC2, MELK, MET, TOP2A). The artificial neural network model (PDAC-ANN) classified the train samples with sensitivity of 0.95, specificity of 0.9, and f1-score of 0.93. The PDAC-ANN could classify the test samples with a sensitivity of 0.97, specificity of 0.88, and f1-score 0.94.ConclusionThe gene expression meta-analysis and confirmation of the protein expression allow us to select five genes highly expressed PDAC samples. We could build a python script to classify the samples based on mRNA expression. This software can be useful in the PDAC diagnosis.

scholarly journals A machine learning algorithm predicts molecular subtypes in pancreatic ductal adenocarcinoma with differential response to gemcitabine-based versus FOLFIRINOX chemotherapy

2019 ◽  
Author(s):  
Georgios Kaissis ◽  
Sebastian Ziegelmayer ◽  
Fabian Lohöfer ◽  
Katja Steiger ◽  
Hana Algül ◽  
...  
Keyword(s):  
Machine Learning ◽  
Overall Survival ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Median Overall Survival ◽  
Molecular Subtypes ◽  
Supervised Machine Learning ◽  
Ductal Adenocarcinoma ◽  
Chemotherapy Response ◽  
Response To Chemotherapy ◽  
Sensitivity Specificity

AbstractPurposeDevelopment of a supervised machine-learning model capable of predicting clinically relevant molecular subtypes of pancreatic ductal adenocarcinoma (PDAC) from diffusion-weighted-imaging-derived radiomic features.MethodsThe retrospective observational study assessed 55 surgical PDAC patients. Molecular subtypes were defined by immunohistochemical staining of KRT81. Tumors were manually segmented and 1606 radiomic features were extracted withPyRadiomics. A gradient-boosted-tree algorithm (XGBoost) was trained on 70% of the patients (N=28) and tested on 30% (N=17) to predict KRT81+ vs. KRT81-tumor subtypes. The average sensitivity, specificity and ROC-AUC value were calculated. Chemotherapy response was assessed stratified by subtype. Radiomic feature importance was ranked.ResultsThe mean±STDEV sensitivity, specificity and ROC-AUC were 0.90±0.07, 0.92±0.11, and 0.93±0.07, respectively. Patients with a KRT81+ subtype experienced significantly diminished median overall survival compared to KRT81-patients (7.0 vs. 22.6 months, HR 1.44, log-rank-test P=<0.001) and a significantly improved response to gemcitabine-based chemotherapy over FOLFIRINOX (10.14 vs. 3.8 months median overall survival, HR 0.85, P=0.037) compared to KRT81-patients, who responded significantly better to FOLFIRINOX over gemcitabine-based treatment (30.8 vs. 13.4 months median overall survival, HR 0.88, P=0.027).ConclusionsThe machine-learning based analysis of radiomic features enables the prediction of subtypes of PDAC, which are highly relevant for overall patient survival and response to chemotherapy.

scholarly journals CT Radiomics and Machine-Learning Models for Predicting Tumor-Stroma Ratio in Patients With Pancreatic Ductal Adenocarcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Yinghao Meng ◽  
Hao Zhang ◽  
Qi Li ◽  
Fang Liu ◽  
Xu Fang ◽  
...  
Keyword(s):  
Machine Learning ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Predictive Value ◽  
Tumor Stroma ◽  
Ductal Adenocarcinoma ◽  
Gradient Boosting ◽  
Rank Test ◽  
Training Set ◽  
Extreme Gradient Boosting ◽  
Validation Set

PurposeTo develop and validate a machine learning classifier based on multidetector computed tomography (MDCT), for the preoperative prediction of tumor–stroma ratio (TSR) expression in patients with pancreatic ductal adenocarcinoma (PDAC).Materials and MethodsIn this retrospective study, 227 patients with PDAC underwent an MDCT scan and surgical resection. We quantified the TSR by using hematoxylin and eosin staining and extracted 1409 arterial and portal venous phase radiomics features for each patient, respectively. Moreover, we used the least absolute shrinkage and selection operator logistic regression algorithm to reduce the features. The extreme gradient boosting (XGBoost) was developed using a training set consisting of 167 consecutive patients, admitted between December 2016 and December 2017. The model was validated in 60 consecutive patients, admitted between January 2018 and April 2018. We determined the XGBoost classifier performance based on its discriminative ability, calibration, and clinical utility.ResultsWe observed low and high TSR in 91 (40.09%) and 136 (59.91%) patients, respectively. A log-rank test revealed significantly longer survival for patients in the TSR-low group than those in the TSR-high group. The prediction model revealed good discrimination in the training (area under the curve [AUC]= 0.93) and moderate discrimination in the validation set (AUC= 0.63). While the sensitivity, specificity, accuracy, positive predictive value, and negative predictive value for the training set were 94.06%, 81.82%, 0.89, 0.89, and 0.90, respectively, those for the validation set were 85.71%, 48.00%, 0.70, 0.70, and 0.71, respectively.ConclusionsThe CT radiomics-based XGBoost classifier provides a potentially valuable noninvasive tool to predict TSR in patients with PDAC and optimize risk stratification.

scholarly journals Image-Based Molecular Phenotyping of Pancreatic Ductal Adenocarcinoma

2020 ◽  
Vol 9 (3) ◽  
pp. 724 ◽  
Author(s):  
Georgios A. Kaissis ◽  
Sebastian Ziegelmayer ◽  
Fabian K. Lohöfer ◽  
Felix N. Harder ◽  
Friederike Jungmann ◽  
...  
Keyword(s):  
Machine Learning ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Learning Algorithm ◽  
Molecular Subtype ◽  
Characteristic Curve ◽  
Ductal Adenocarcinoma ◽  
Rank Test ◽  
Learning Approaches ◽  
Imaging Data ◽  
Log Rank Test

To bridge the translational gap between recent discoveries of distinct molecular phenotypes of pancreatic cancer and tangible improvements in patient outcome, there is an urgent need to develop strategies and tools informing and improving the clinical decision process. Radiomics and machine learning approaches can offer non-invasive whole tumor analytics for clinical imaging data-based classification. The retrospective study assessed baseline computed tomography (CT) from 207 patients with proven pancreatic ductal adenocarcinoma (PDAC). Following expert level manual annotation, Pyradiomics was used for the extraction of 1474 radiomic features. The molecular tumor subtype was defined by immunohistochemical staining for KRT81 and HNF1a as quasi-mesenchymal (QM) vs. non-quasi-mesenchymal (non-QM). A Random Forest machine learning algorithm was developed to predict the molecular subtype from the radiomic features. The algorithm was then applied to an independent cohort of histopathologically unclassifiable tumors with distinct clinical outcomes. The classification algorithm achieved a sensitivity, specificity and ROC-AUC (area under the receiver operating characteristic curve) of 0.84 ± 0.05, 0.92 ± 0.01 and 0.93 ± 0.01, respectively. The median overall survival for predicted QM and non-QM tumors was 16.1 and 20.9 months, respectively, log-rank-test p = 0.02, harzard ratio (HR) 1.59. The application of the algorithm to histopathologically unclassifiable tumors revealed two groups with significantly different survival (8.9 and 39.8 months, log-rank-test p < 0.001, HR 4.33). The machine learning-based analysis of preoperative (CT) imaging allows the prediction of molecular PDAC subtypes highly relevant for patient survival, allowing advanced pre-operative patient stratification for precision medicine applications.

scholarly journals A machine learning model for the prediction of survival and tumor subtype in pancreatic ductal adenocarcinoma from preoperative diffusion-weighted imaging

2019 ◽  
Vol 3 (1) ◽  
Author(s):  
Georgios Kaissis ◽  
Sebastian Ziegelmayer ◽  
Fabian Lohöfer ◽  
Hana Algül ◽  
Matthias Eiber ◽  
...  
Keyword(s):  
Machine Learning ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Diffusion Weighted Imaging ◽  
Area Under The Curve ◽  
Supervised Machine Learning ◽  
Ductal Adenocarcinoma ◽  
Recursive Feature Elimination ◽  
Training Cohort ◽  
Diffusion Weighted ◽  
Histopathological Subtype

Abstract Background To develop a supervised machine learning (ML) algorithm predicting above- versus below-median overall survival (OS) from diffusion-weighted imaging-derived radiomic features in patients with pancreatic ductal adenocarcinoma (PDAC). Methods One hundred two patients with histopathologically proven PDAC were retrospectively assessed as training cohort, and 30 prospectively accrued and retrospectively enrolled patients served as independent validation cohort (IVC). Tumors were segmented on preoperative apparent diffusion coefficient (ADC) maps, and radiomic features were extracted. A random forest ML algorithm was fit to the training cohort and tested in the IVC. Histopathological subtype of tumor samples was assessed by immunohistochemistry in 21 IVC patients. Individual radiomic feature importance was evaluated by assessment of tree node Gini impurity decrease and recursive feature elimination. Fisher’s exact test, 95% confidence intervals (CI), and receiver operating characteristic area under the curve (ROC-AUC) were used. Results The ML algorithm achieved 87% sensitivity (95% IC 67.3–92.7), 80% specificity (95% CI 74.0–86.7), and ROC-AUC 90% for the prediction of above- versus below-median OS in the IVC. Heterogeneity-related features were highly ranked by the model. Of the 21 patients with determined histopathological subtype, 8/9 patients predicted to experience below-median OS exhibited the quasi-mesenchymal subtype, whilst 11/12 patients predicted to experience above-median OS exhibited a non-quasi-mesenchymal subtype (p < 0.001). Conclusion ML application to ADC radiomics allowed OS prediction with a high diagnostic accuracy in an IVC. The high overlap of clinically relevant histopathological subtypes with model predictions underlines the potential of quantitative imaging in PDAC pre-operative subtyping and prognosis.

scholarly journals Multi-institutional development and external validation of machine learning-based models to predict relapse risk of pancreatic ductal adenocarcinoma after radical resection

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Xiawei Li ◽  
Litao Yang ◽  
Zheping Yuan ◽  
Jianyao Lou ◽  
Yiqun Fan ◽  
...  
Keyword(s):  
Machine Learning ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Institutional Development ◽  
Radical Resection ◽  
Ductal Adenocarcinoma ◽  
Support Vector ◽  
Training Set ◽  
Relapse Risk ◽  
Validation Set ◽  
Risk Of Relapse

Abstract Background Surgical resection is the only potentially curative treatment for pancreatic ductal adenocarcinoma (PDAC) and the survival of patients after radical resection is closely related to relapse. We aimed to develop models to predict the risk of relapse using machine learning methods based on multiple clinical parameters. Methods Data were collected and analysed of 262 PDAC patients who underwent radical resection at 3 institutions between 2013 and 2017, with 183 from one institution as a training set, 79 from the other 2 institution as a validation set. We developed and compared several predictive models to predict 1- and 2-year relapse risk using machine learning approaches. Results Machine learning techniques were superior to conventional regression-based analyses in predicting risk of relapse of PDAC after radical resection. Among them, the random forest (RF) outperformed other methods in the training set. The highest accuracy and area under the receiver operating characteristic curve (AUROC) for predicting 1-year relapse risk with RF were 78.4% and 0.834, respectively, and for 2-year relapse risk were 95.1% and 0.998. However, the support vector machine (SVM) model showed better performance than the others for predicting 1-year relapse risk in the validation set. And the k neighbor algorithm (KNN) model achieved the highest accuracy and AUROC for predicting 2-year relapse risk. Conclusions By machine learning, this study has developed and validated comprehensive models integrating clinicopathological characteristics to predict the relapse risk of PDAC after radical resection which will guide the development of personalized surveillance programs after surgery.

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