An Efficient Lightweight CNN and Ensemble Machine Learning Classification of Prostate Tissue Using Multilevel Feature Analysis

Prostate carcinoma is caused when cells and glands in the prostate change their shape and size from normal to abnormal. Typically, the pathologist’s goal is to classify the staining slides and differentiate normal from abnormal tissue. In the present study, we used a computational approach to classify images and features of benign and malignant tissues using artificial intelligence (AI) techniques. Here, we introduce two lightweight convolutional neural network (CNN) architectures and an ensemble machine learning (EML) method for image and feature classification, respectively. Moreover, the classification using pre-trained models and handcrafted features was carried out for comparative analysis. The binary classification was performed to classify between the two grade groups (benign vs. malignant) and quantile-quantile plots were used to show their predicted outcomes. Our proposed models for deep learning (DL) and machine learning (ML) classification achieved promising accuracies of 94.0% and 92.0%, respectively, based on non-handcrafted features extracted from CNN layers. Therefore, these models were able to predict nearly perfectly accurately using few trainable parameters or CNN layers, highlighting the importance of DL and ML techniques and suggesting that the computational analysis of microscopic anatomy will be essential to the future practice of pathology.

deMeta: Removing sub-studies from meta-analysis of genome wide association studies (GWAS)

ABSTRACTSummaryPost-GWAS studies using the results from large consortium meta-analysis often need to correctly take care of the overlapping sample issue. The gold standard approach for resolving this issue is to reperform the GWAS or meta-analysis excluding the overlapped participants. However, such approach is time-consuming and, sometimes, restricted by the available data. deMeta provides a user friendly and computationally efficient command-line implementation for removing the effect of a contributing sub-study to a consortium from the meta-analysis results. Only the summary statistics of the meta-analysis the sub-study to be removed are required. In addition, deMeta can generate contrasting Manhattan and quantile-quantile plots for users to visualize the impact of the sub-study on the meta-analysis results.Availability and ImplementationThe python source code, examples and documentations of deMeta are publicly available at https://github.com/Computational-NeuroGenetics/[email protected] (J. Sun); [email protected] (Y. Wang)Supplementary informationNone.

SAMPL6 Challenge Results from pKa Predictions Based on a General Gaussian Process Model

<div>A variety of fields would benefit from accurate pK_a predictions, especially drug design due to the affect a change in ionization state can have on a molecules physiochemical properties.</div><div>Participants in the recent SAMPL6 blind challenge were asked to submit predictions for microscopic and macroscopic pK_as of 24 drug like small molecules.</div><div>We recently built a general model for predicting pK_as using a Gaussian process regression trained using physical and chemical features of each ionizable group.</div><div>Our pipeline takes a molecular graph and uses the OpenEye Toolkits to calculate features describing the removal of a proton.</div><div>These features are fed into a Scikit-learn Gaussian process to predict microscopic pK_as which are then used to analytically determine macroscopic pK_as.</div><div>Our Gaussian process is trained on a set of 2,700 macroscopic pK_as from monoprotic and select diprotic molecules.</div><div>Here, we share our results for microscopic and macroscopic predictions in the SAMPL6 challenge.</div><div>Overall, we ranked in the middle of the pack compared to other participants, but our fairly good agreement with experiment is still promising considering the challenge molecules are chemically diverse and often polyprotic while our training set is predominately monoprotic.</div><div>Of particular importance to us when building this model was to include an uncertainty estimate based on the chemistry of the molecule that would reflect the likely accuracy of our prediction. </div><div>Our model reports large uncertainties for the molecules that appear to have chemistry outside our domain of applicability, along with good agreement in quantile-quantile plots, indicating it can predict its own accuracy.</div><div>The challenge highlighted a variety of means to improve our model, including adding more polyprotic molecules to our training set and more carefully considering what functional groups we do or do not identify as ionizable. </div>

SAMPL6 Challenge Results from pKa Predictions Based on a General Gaussian Process Model

<div>A variety of fields would benefit from accurate pK_a predictions, especially drug design due to the affect a change in ionization state can have on a molecules physiochemical properties.</div><div>Participants in the recent SAMPL6 blind challenge were asked to submit predictions for microscopic and macroscopic pK_as of 24 drug like small molecules.</div><div>We recently built a general model for predicting pK_as using a Gaussian process regression trained using physical and chemical features of each ionizable group.</div><div>Our pipeline takes a molecular graph and uses the OpenEye Toolkits to calculate features describing the removal of a proton.</div><div>These features are fed into a Scikit-learn Gaussian process to predict microscopic pK_as which are then used to analytically determine macroscopic pK_as.</div><div>Our Gaussian process is trained on a set of 2,700 macroscopic pK_as from monoprotic and select diprotic molecules.</div><div>Here, we share our results for microscopic and macroscopic predictions in the SAMPL6 challenge.</div><div>Overall, we ranked in the middle of the pack compared to other participants, but our fairly good agreement with experiment is still promising considering the challenge molecules are chemically diverse and often polyprotic while our training set is predominately monoprotic.</div><div>Of particular importance to us when building this model was to include an uncertainty estimate based on the chemistry of the molecule that would reflect the likely accuracy of our prediction. </div><div>Our model reports large uncertainties for the molecules that appear to have chemistry outside our domain of applicability, along with good agreement in quantile-quantile plots, indicating it can predict its own accuracy.</div><div>The challenge highlighted a variety of means to improve our model, including adding more polyprotic molecules to our training set and more carefully considering what functional groups we do or do not identify as ionizable. </div>

SAMPL6 Challenge Results from pKa Predictions Based on a General Gaussian Process Model

<div>A variety of fields would benefit from accurate pK_a predictions, especially drug design due to the affect a change in ionization state can have on a molecules physiochemical properties.</div><div>Participants in the recent SAMPL6 blind challenge were asked to submit predictions for microscopic and macroscopic pK_as of 24 drug like small molecules.</div><div>We recently built a general model for predicting pK_as using a Gaussian process regression trained using physical and chemical features of each ionizable group.</div><div>Our pipeline takes a molecular graph and uses the OpenEye Toolkits to calculate features describing the removal of a proton.</div><div>These features are fed into a Scikit-learn Gaussian process to predict microscopic pK_as which are then used to analytically determine macroscopic pK_as.</div><div>Our Gaussian process is trained on a set of 2,700 macroscopic pK_as from monoprotic and select diprotic molecules.</div><div>Here, we share our results for microscopic and macroscopic predictions in the SAMPL6 challenge.</div><div>Overall, we ranked in the middle of the pack compared to other participants, but our fairly good agreement with experiment is still promising considering the challenge molecules are chemically diverse and often polyprotic while our training set is predominately monoprotic.</div><div>Of particular importance to us when building this model was to include an uncertainty estimate based on the chemistry of the molecule that would reflect the likely accuracy of our prediction. </div><div>Our model reports large uncertainties for the molecules that appear to have chemistry outside our domain of applicability, along with good agreement in quantile-quantile plots, indicating it can predict its own accuracy.</div><div>The challenge highlighted a variety of means to improve our model, including adding more polyprotic molecules to our training set and more carefully considering what functional groups we do or do not identify as ionizable. </div>

Explorations in statistics: the assumption of normality

Learning about statistics is a lot like learning about science: the learning is more meaningful if you can actively explore. This twelfth installment of Explorations in Statistics explores the assumption of normality, an assumption essential to the meaningful interpretation of a t test. Although the data themselves can be consistent with a normal distribution, they need not be. Instead, it is the theoretical distribution of the sample mean or the theoretical distribution of the difference between sample means that must be roughly normal. The most versatile approach to assess normality is to bootstrap the sample mean, the difference between sample means, or t itself. We can then assess whether the distributions of these bootstrap statistics are consistent with a normal distribution by studying their normal quantile plots. If we suspect that an inference we make from a t test may not be justified—if we suspect that the theoretical distribution of the sample mean or the theoretical distribution of the difference between sample means is not normal—then we can use a permutation method to analyze our data.