scholarly journals 3145 An Evaluation of Machine Learning and Traditional Statistical Methods for Discovery in Large-Scale Translational Data

2019 ◽  
Vol 3 (s1) ◽  
pp. 2-2
Author(s):  
Megan C Hollister ◽  
Jeffrey D. Blume
Keyword(s):  
Gene Expression ◽  
Machine Learning ◽  
Random Forest ◽  
Gene Expression Data ◽  
Large Scale ◽  
Second Generation ◽  
A Priori ◽  
Expression Data ◽  
P Values ◽  
Machine Learning Methods

OBJECTIVES/SPECIFIC AIMS: To examine and compare the claims in Bzdok, Altman, and Brzywinski under a broader set of conditions by using unbiased methods of comparison. To explore how to accurately use various machine learning and traditional statistical methods in large-scale translational research by estimating their accuracy statistics. Then we will identify the methods with the best performance characteristics. METHODS/STUDY POPULATION: We conducted a simulation study with a microarray of gene expression data. We maintained the original structure proposed by Bzdok, Altman, and Brzywinski. The structure for gene expression data includes a total of 40 genes from 20 people, in which 10 people are phenotype positive and 10 are phenotype negative. In order to find a statistical difference 25% of the genes were set to be dysregulated across phenotype. This dysregulation forced the positive and negative phenotypes to have different mean population expressions. Additional variance was included to simulate genetic variation across the population. We also allowed for within person correlation across genes, which was not done in the original simulations. The following methods were used to determine the number of dysregulated genes in simulated data set: unadjusted p-values, Benjamini-Hochberg adjusted p-values, Bonferroni adjusted p-values, random forest importance levels, neural net prediction weights, and second-generation p-values. RESULTS/ANTICIPATED RESULTS: Results vary depending on whether a pre-specified significance level is used or the top 10 ranked values are taken. When all methods are given the same prior information of 10 dysregulated genes, the Benjamini-Hochberg adjusted p-values and the second-generation p-values generally outperform all other methods. We were not able to reproduce or validate the finding that random forest importance levels via a machine learning algorithm outperform classical methods. Almost uniformly, the machine learning methods did not yield improved accuracy statistics and they depend heavily on the a priori chosen number of dysregulated genes. DISCUSSION/SIGNIFICANCE OF IMPACT: In this context, machine learning methods do not outperform standard methods. Because of this and their additional complexity, machine learning approaches would not be preferable. Of all the approaches the second-generation p-value appears to offer significant benefit for the cost of a priori defining a region of trivially null effect sizes. The choice of an analysis method for large-scale translational data is critical to the success of any statistical investigation, and our simulations clearly highlight the various tradeoffs among the available methods.

scholarly journals Maximizing the Reusability of Public Gene Expression Data by Predicting Missing Metadata

2019 ◽  
Author(s):  
Pei-Yau Lung ◽  
Xiaodong Pang ◽  
Yan Li ◽  
Jinfeng Zhang
Keyword(s):  
Gene Expression ◽  
Machine Learning ◽  
Gene Expression Data ◽  
Missing Values ◽  
Expression Data ◽  
New Approach ◽  
Machine Learning Methods ◽  
Differential Gene ◽  
Missing Variables ◽  
Better Than

AbstractReusability is part of the FAIR data principle, which aims to make data Findable, Accessible, Interoperable, and Reusable. One of the current efforts to increase the reusability of public genomics data has been to focus on the inclusion of quality metadata associated with the data. When necessary metadata are missing, most researchers will consider the data useless. In this study, we develop a framework to predict the missing metadata of gene expression datasets to maximize their reusability. We propose a new metric called Proportion of Cases Accurately Predicted (PCAP), which is optimized in our specifically-designed machine learning pipeline. The new approach performed better than pipelines using commonly used metrics such as F1-score in terms of maximizing the reusability of data with missing values. We also found that different variables might need to be predicted using different machine learning methods and/or different data processing protocols. Using differential gene expression analysis as an example, we show that when missing variables are accurately predicted, the corresponding gene expression data can be reliably used in downstream analyses.

scholarly journals Maximizing the reusability of gene expression data by predicting missing metadata

2020 ◽  
Vol 16 (11) ◽  
pp. e1007450
Author(s):  
Pei-Yau Lung ◽  
Dongrui Zhong ◽  
Xiaodong Pang ◽  
Yan Li ◽  
Jinfeng Zhang
Keyword(s):  
Gene Expression ◽  
Machine Learning ◽  
Gene Expression Data ◽  
Missing Values ◽  
Expression Data ◽  
New Approach ◽  
Machine Learning Methods ◽  
Differential Gene ◽  
Missing Variables ◽  
Better Than

Reusability is part of the FAIR data principle, which aims to make data Findable, Accessible, Interoperable, and Reusable. One of the current efforts to increase the reusability of public genomics data has been to focus on the inclusion of quality metadata associated with the data. When necessary metadata are missing, most researchers will consider the data useless. In this study, we developed a framework to predict the missing metadata of gene expression datasets to maximize their reusability. We found that when using predicted data to conduct other analyses, it is not optimal to use all the predicted data. Instead, one should only use the subset of data, which can be predicted accurately. We proposed a new metric called Proportion of Cases Accurately Predicted (PCAP), which is optimized in our specifically-designed machine learning pipeline. The new approach performed better than pipelines using commonly used metrics such as F1-score in terms of maximizing the reusability of data with missing values. We also found that different variables might need to be predicted using different machine learning methods and/or different data processing protocols. Using differential gene expression analysis as an example, we showed that when missing variables are accurately predicted, the corresponding gene expression data can be reliably used in downstream analyses.

scholarly journals Graph Convolutional Network for Drug Response Prediction Using Gene Expression Data

Mathematics ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 772
Author(s):  
Seonghun Kim ◽  
Seockhun Bae ◽  
Yinhua Piao ◽  
Kyuri Jo
Keyword(s):  
Gene Expression ◽  
Gene Expression Data ◽  
Large Scale ◽  
Drug Response ◽  
Response Prediction ◽  
Biological Data ◽  
Expression Data ◽  
Convolutional Network ◽  
Essential Information ◽  
Protein Protein Interaction

Genomic profiles of cancer patients such as gene expression have become a major source to predict responses to drugs in the era of personalized medicine. As large-scale drug screening data with cancer cell lines are available, a number of computational methods have been developed for drug response prediction. However, few methods incorporate both gene expression data and the biological network, which can harbor essential information about the underlying process of the drug response. We proposed an analysis framework called DrugGCN for prediction of Drug response using a Graph Convolutional Network (GCN). DrugGCN first generates a gene graph by combining a Protein-Protein Interaction (PPI) network and gene expression data with feature selection of drug-related genes, and the GCN model detects the local features such as subnetworks of genes that contribute to the drug response by localized filtering. We demonstrated the effectiveness of DrugGCN using biological data showing its high prediction accuracy among the competing methods.

scholarly journals A method of gene expression data transfer from cell lines to cancer patients for machine-learning prediction of drug efficiency

Cell Cycle ◽  
2018 ◽  
Vol 17 (4) ◽  
pp. 486-491 ◽  
Author(s):  
Nicolas Borisov ◽  
Victor Tkachev ◽  
Maria Suntsova ◽  
Olga Kovalchuk ◽  
Alex Zhavoronkov ◽  
...  
Keyword(s):  
Gene Expression ◽  
Machine Learning ◽  
Cancer Patients ◽  
Cell Lines ◽  
Gene Expression Data ◽  
Data Transfer ◽  
Expression Data ◽  
Drug Efficiency

scholarly journals Inference of Genetic Networks From Time-Series and Static Gene Expression Data: Combining a Random-Forest-Based Inference Method With Feature Selection Methods

2020 ◽  
Vol 11 ◽  
Author(s):  
Shuhei Kimura ◽  
Ryo Fukutomi ◽  
Masato Tokuhisa ◽  
Mariko Okada
Keyword(s):  
Gene Expression ◽  
Feature Selection ◽  
Random Forest ◽  
Gene Expression Data ◽  
Computational Cost ◽  
Expression Data ◽  
Selection Methods ◽  
Inference Method ◽  
Combined Application ◽  
Inference Methods

Several researchers have focused on random-forest-based inference methods because of their excellent performance. Some of these inference methods also have a useful ability to analyze both time-series and static gene expression data. However, they are only of use in ranking all of the candidate regulations by assigning them confidence values. None have been capable of detecting the regulations that actually affect a gene of interest. In this study, we propose a method to remove unpromising candidate regulations by combining the random-forest-based inference method with a series of feature selection methods. In addition to detecting unpromising regulations, our proposed method uses outputs from the feature selection methods to adjust the confidence values of all of the candidate regulations that have been computed by the random-forest-based inference method. Numerical experiments showed that the combined application with the feature selection methods improved the performance of the random-forest-based inference method on 99 of the 100 trials performed on the artificial problems. However, the improvement tends to be small, since our combined method succeeded in removing only 19% of the candidate regulations at most. The combined application with the feature selection methods moreover makes the computational cost higher. While a bigger improvement at a lower computational cost would be ideal, we see no impediments to our investigation, given that our aim is to extract as much useful information as possible from a limited amount of gene expression data.

scholarly journals LSTrAP-Crowd: Prediction of novel components of bacterial ribosomes with crowd-sourced analysis of RNA sequencing data

2020 ◽  
Author(s):  
Benedict Hew ◽  
Qiao Wen Tan ◽  
William Goh ◽  
Jonathan Wei Xiong Ng ◽  
Kenny Koh ◽  
...  
Keyword(s):  
Gene Expression ◽  
Protein Synthesis ◽  
Rna Sequencing ◽  
Gene Expression Data ◽  
Large Scale ◽  
Bacterial Resistance ◽  
Expression Data ◽  
Sequencing Data ◽  
Novel Proteins ◽  
Novel Antibiotics

AbstractBacterial resistance to antibiotics is a growing problem that is projected to cause more deaths than cancer in 2050. Consequently, novel antibiotics are urgently needed. Since more than half of the available antibiotics target the bacterial ribosomes, proteins that are involved in protein synthesis are thus prime targets for the development of novel antibiotics. However, experimental identification of these potential antibiotic target proteins can be labor-intensive and challenging, as these proteins are likely to be poorly characterized and specific to few bacteria. In order to identify these novel proteins, we established a Large-Scale Transcriptomic Analysis Pipeline in Crowd (LSTrAP-Crowd), where 285 individuals processed 26 terabytes of RNA-sequencing data of the 17 most notorious bacterial pathogens. In total, the crowd processed 26,269 RNA-seq experiments and used the data to construct gene co-expression networks, which were used to identify more than a hundred uncharacterized genes that were transcriptionally associated with protein synthesis. We provide the identity of these genes together with the processed gene expression data. The data can be used to identify other vulnerabilities or bacteria, while our approach demonstrates how the processing of gene expression data can be easily crowdsourced.

scholarly journals Defining transcription modules using large-scale gene expression data

2004 ◽  
Vol 20 (13) ◽  
pp. 1993-2003 ◽  
Author(s):  
J. Ihmels ◽  
S. Bergmann ◽  
N. Barkai
Keyword(s):  
Gene Expression ◽  
Gene Expression Data ◽  
Large Scale ◽  
Expression Data
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