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Register a new userA critical evaluation of network and pathway based classifiers for outcome prediction in breast cancer
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Recently, several classifiers that combine primary tumor data, like gene expression data, and secondary data sources, such as protein-protein interaction networks, have been proposed for predicting outcome in breast cancer. In these approaches, new composite features are typically constructed by aggregating the expression levels of several genes. The secondary data sources are employed to guide this aggregation. Although many studies claim that these approaches improve classification performance over single gene classifiers, the gain in performance is difficult to assess. This stems mainly from the fact that different breast cancer data sets and validation procedures are employed to assess the performance. Here we address these issues by employing a large cohort of six breast cancer data sets as benchmark set and by performing an unbiased evaluation of the classification accuracies of the different approaches. Contrary to previous claims, we find that composite feature classifiers do not outperform simple single gene classifiers. We investigate the effect of (1) the number of selected features; (2) the specific gene set from which features are selected; (3) the size of the training set and (4) the heterogeneity of the data set on the performance of composite feature and single gene classifiers. Strikingly, we find that randomization of secondary data sources, which destroys all biological information in these sources, does not result in a deterioration in performance of composite feature classifiers. Finally, we show that when a proper correction for gene set size is performed, the stability of single gene sets is similar to the stability of composite feature sets. Based on these results there is currently no reason to prefer prognostic classifiers based on composite features over single gene classifiers for predicting outcome in breast cancer.
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Deep neural networks (DNNs) show promise in breast cancer screening, but their robustness to input perturbations must be better understood before they can be clinically implemented. There exists extensive literature on this subject in the context of natural images that can potentially be built upon. However, it cannot be assumed that conclusions about robustness will transfer from natural images to mammogram images, due to significant differences between the two image modalities. In order to determine whether conclusions will transfer, we measure the sensitivity of a radiologist-level screening mammogram image classifier to four commonly studied input perturbations that natural image classifiers are sensitive to. We find that mammogram image classifiers are also sensitive to these perturbations, which suggests that we can build on the existing literature. We also perform a detailed analysis on the effects of low-pass filtering, and find that it degrades the visibility of clinically meaningful features called microcalcifications. Since low-pass filtering removes semantically meaningful information that is predictive of breast cancer, we argue that it is undesirable for mammogram image classifiers to be invariant to it. This is in contrast to natural images, where we do not want DNNs to be sensitive to low-pass filtering due to its tendency to remove information that is human-incomprehensible.
This report assesses different machine learning approaches to 10-year survival prediction of breast cancer patients.
Since microRNAs (miRNAs) play a crucial role in post-transcriptional gene regulation, miRNA identification is one of the most essential problems in computational biology. miRNAs are usually short in length ranging between 20 and 23 base pairs. It is thus often difficult to distinguish miRNA-encoding sequences from other non-coding RNAs and pseudo miRNAs that have a similar length, and most previous studies have recommended using precursor miRNAs instead of mature miRNAs for robust detection. A great number of conventional machine-learning-based classification methods have been proposed, but they often have the serious disadvantage of requiring manual feature engineering, and their performance is limited as well. In this paper, we propose a novel miRNA precursor prediction algorithm, deepMiRGene, based on recurrent neural networks, specifically long short-term memory networks. deepMiRGene automatically learns suitable features from the data themselves without manual feature engineering and constructs a model that can successfully reflect structural characteristics of precursor miRNAs. For the performance evaluation of our approach, we have employed several widely used evaluation metrics on three recent benchmark datasets and verified that deepMiRGene delivered comparable performance among the current state-of-the-art tools.
Absorption, distribution, metabolism, and excretion (ADME) studies are critical for drug discovery. Conventionally, these tasks, together with other chemical property predictions, rely on domain-specific feature descriptors, or fingerprints. Following the recent success of neural networks, we developed Chemi-Net, a completely data-driven, domain knowledge-free, deep learning method for ADME property prediction. To compare the relative performance of Chemi-Net with Cubist, one of the popular machine learning programs used by Amgen, a large-scale ADME property prediction study was performed on-site at Amgen. The results showed that our deep neural network method improved current methods by a large margin. We foresee that the significantly increased accuracy of ADME prediction seen with Chemi-Net over Cubist will greatly accelerate drug discovery.
Breast cancer is the most frequently reported cancer type among the women around the globe and beyond that it has the second highest female fatality rate among all cancer types. Despite all the progresses made in prevention and early intervention, early prognosis and survival prediction rates are still unsatisfactory. In this paper, we propose a novel type of perceptron called L-Perceptron which outperforms all the previous supervised learning methods by reaching 97.42 % and 98.73 % in terms of accuracy and sensitivity, respectively in Wisconsin Breast Cancer dataset. Experimental results on Habermans Breast Cancer Survival dataset, show the superiority of proposed method by reaching 75.18 % and 83.86 % in terms of accuracy and F1 score, respectively. The results are the best reported ones obtained in 10-fold cross validation in absence of any preprocessing or feature selection.
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