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

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.

2020 ◽  
Author(s):  
Jibril Abdulsalam ◽  
Abiodun Ismail Lawal ◽  
Ramadimetja Lizah Setsepu ◽  
Moshood Onifade ◽  
Samson Bada

Abstract Globally, the provision of energy is becoming an absolute necessity. Biomass resources are abundant and have been described as a potential alternative source of energy. However, it is important to assess the fuel characteristics of the various available biomass sources. Soft computing techniques are presented in this study to predict the mass yield (MY), energy yield (EY), and higher heating value (HHV) of hydrothermally carbonized biomass by using Gene Expression Programming (GEP), multiple-input single output-artificial neural network (MISO-ANN), and Multilinear regression (MLR). The three techniques were compared using statistical performance metrics. The coefficient of determination (R2), mean absolute error (MAE), and mean bias error (MBE) were used to evaluate the performance of the models. The MISO-ANN with 5-10-10-1 and 5-15-15-1 network architectures provided the most satisfactory performance of the three proposed models (R2 = 0.976, 0.955, 0.996; MAE = 2.24, 2.11, 0.93; MBE = 0.16, 0.37, 0.12) for MY, EY and HHV respectively. The GEP technique’s ability to predict hydrochar properties based on the input parameters was found to be satisfactory, while MLR provided an unsatisfactory predictive model. Sensitivity analysis was conducted, and the analysis revealed that volatile matter (VM) and temperature (Temp) have more influence on the MY, EY, and HHV.


2018 ◽  
Author(s):  
Vandana Sandhu ◽  
Knut Jorgen Labori ◽  
Ayelet Borgida ◽  
Ilinca Lungu ◽  
John Bartlett ◽  
...  

ABSTRACTBackgroundWith a dismal 8% median 5-year overall survival (OS), pancreatic ductal adenocarcinoma (PDAC) is highly lethal. Only 10-20% of patients are eligible for surgery, and over 50% of these will die within a year of surgery. Identify molecular predictors of early death would enable the selection of PDAC patients at high risk.MethodsWe developed the Pancreatic Cancer Overall Survival Predictor (PCOSP), a prognostic model built from a unique set of 89 PDAC tumors where gene expression was profiled using both microarray and sequencing platforms. We used a meta-analysis framework based on the binary gene pair method to create gene expression barcodes robust to biases arising from heterogeneous profiling platforms and batch effects. Leveraging the largest compendium of PDAC transcriptomic datasets to date, we show that PCOSP is a robust single-sample predictor of early death (≤1 yr) after surgery in a subset of 823 samples with available transcriptomics and survival data.ResultsThe PCOSP model was strongly and significantly prognostic with a meta-estimate of the area under the receiver operating curve (AUROC) of 0.70 (P=1.9e-18) and hazard ratio (HR) of 1.95(1.6-2.3) (P=2.6e-16) for binary and survival predictions, respectively. The prognostic value of PCOSP was independent of clinicopathological parameters and molecular subtypes. Over-representation analysis of the PCOSP 2619 gene-pairs (1070 unique genes) unveiled pathways associated with Hedgehog signalling, epithelial mesenchymal transition (EMT) and extracellular matrix (ECM) signalling.ConclusionPCOSP could improve treatment decision by identifying patients who will not benefit from standard surgery/chemotherapy and may benefit from alternate approaches.AbbreviationsAUROCArea under the receiver operating curveGOGene annotationOSOverall survivalPCOSPPancreatic cancer overall survival predictorPDACPancreatic ductal adenocarcinomaTSPTop scoring pairs.


2018 ◽  
Vol 2018 ◽  
pp. 1-15
Author(s):  
Davide Perruzza ◽  
Nicola Bernabò ◽  
Cinzia Rapino ◽  
Luca Valbonetti ◽  
Ilaria Falanga ◽  
...  

The relationship between varicocele and fertility has always been a matter of debate because of the absence of predictive clinical indicators or molecular markers able to define the severity of this disease. Even though accumulated evidence demonstrated that the endocannabinoid system (ECS) plays a central role in male reproductive biology, particularly in the testicular compartment, to date no data point to a role for ECS in the etiopathogenesis of varicocele. Therefore, the present research has been designed to investigate the relationship between testicular ECS gene expression and fertility, using a validated animal model of experimental varicocele (VAR), taking advantage of traditional statistical approaches and artificial neural network (ANN). Experimental induction of VAR led to a clear reduction of spermatogenesis in left testes ranging from a mild (Johnsen score 7: 21%) to a severe (Johnsen score 4: 58%) damage of the germinal epithelium. However, the mean number of new-borns recorded after two sequential matings was quite variable and independent of the Johnsen score. While the gene expression of biosynthetic and degrading enzymes of AEA (NAPE-PLD and FAAH, respectively) and of 2-AG (DAGLα and MAGL, respectively), as well as their binding cannabinoid receptors (CB1 and CB2), did not change between testes and among groups, a significant downregulation of vanilloid (TRPV1) expression was recorded in left testes of VAR rats and positively correlated with animal fertility. Interestingly, an ANN trained by inserting the left and right testicular ECS gene expression profiles (inputs) was able to predict varicocele impact on male fertility in terms of mean number of new-borns delivered (outputs), with a very high accuracy (average prediction error of 1%). The present study provides unprecedented information on testicular ECS gene expression patterns during varicocele, by developing a freely available predictive ANN model that may open new perspectives in the diagnosis of varicocele-associated infertility.


2018 ◽  
Vol 35 (13) ◽  
pp. 2226-2234 ◽  
Author(s):  
Ameen Eetemadi ◽  
Ilias Tagkopoulos

Abstract Motivation Gene expression prediction is one of the grand challenges in computational biology. The availability of transcriptomics data combined with recent advances in artificial neural networks provide an unprecedented opportunity to create predictive models of gene expression with far reaching applications. Results We present the Genetic Neural Network (GNN), an artificial neural network for predicting genome-wide gene expression given gene knockouts and master regulator perturbations. In its core, the GNN maps existing gene regulatory information in its architecture and it uses cell nodes that have been specifically designed to capture the dependencies and non-linear dynamics that exist in gene networks. These two key features make the GNN architecture capable to capture complex relationships without the need of large training datasets. As a result, GNNs were 40% more accurate on average than competing architectures (MLP, RNN, BiRNN) when compared on hundreds of curated and inferred transcription modules. Our results argue that GNNs can become the architecture of choice when building predictors of gene expression from exponentially growing corpus of genome-wide transcriptomics data. Availability and implementation https://github.com/IBPA/GNN Supplementary information Supplementary data are available at Bioinformatics online.


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