scholarly journals MatchMixeR: a cross-platform normalization method for gene expression data integration

2020 ◽  
Vol 36 (8) ◽  
pp. 2486-2491 ◽  
Author(s):  
Serin Zhang ◽  
Jiang Shao ◽  
Disa Yu ◽  
Xing Qiu ◽  
Jinfeng Zhang
Keyword(s):  
Gene Expression ◽  
R Package ◽  
Supplementary Information ◽  
Computationally Efficient ◽  
Trade Off ◽  
Novel Approach ◽  
Cross Platform ◽  
The Moment ◽  
Model Platform ◽  
Biological Differences

Abstract Motivation Combining gene expression (GE) profiles generated from different platforms enables previously infeasible studies due to sample size limitations. Several cross-platform normalization methods have been developed to remove the systematic differences between platforms, but they may also remove meaningful biological differences among datasets. In this work, we propose a novel approach that removes the platform, not the biological differences. Dubbed as ‘MatchMixeR’, we model platform differences by a linear mixed effects regression (LMER) model, and estimate them from matched GE profiles of the same cell line or tissue measured on different platforms. The resulting model can then be used to remove platform differences in other datasets. By using LMER, we achieve better bias-variance trade-off in parameter estimation. We also design a computationally efficient algorithm based on the moment method, which is ideal for ultra-high-dimensional LMER analysis. Results Compared with several prominent competing methods, MatchMixeR achieved the highest after-normalization concordance. Subsequent differential expression analyses based on datasets integrated from different platforms showed that using MatchMixeR achieved the best trade-off between true and false discoveries, and this advantage is more apparent in datasets with limited samples or unbalanced group proportions. Availability and implementation Our method is implemented in a R-package, ‘MatchMixeR’, freely available at: https://github.com/dy16b/Cross-Platform-Normalization. Supplementary information Supplementary data are available at Bioinformatics online.

scholarly journals Space-log: a novel approach to inferring gene-gene net-works using SPACE model with log penalty

F1000Research ◽  
2022 ◽  
Vol 9 ◽  
pp. 1159
Author(s):  
Qian (Vicky) Wu ◽  
Wei Sun ◽  
Li Hsu
Keyword(s):  
Gene Expression ◽  
Gene Expression Data ◽  
Gene Networks ◽  
Regulatory Networks ◽  
Penalized Regression ◽  
R Package ◽  
Expression Data ◽  
Computationally Efficient ◽  
P Gene ◽  
Novel Approach

Gene expression data have been used to infer gene-gene networks (GGN) where an edge between two genes implies the conditional dependence of these two genes given all the other genes. Such gene-gene networks are of-ten referred to as gene regulatory networks since it may reveal expression regulation. Most of existing methods for identifying GGN employ penalized regression with L1 (lasso), L2 (ridge), or elastic net penalty, which spans the range of L1 to L2 penalty. However, for high dimensional gene expression data, a penalty that spans the range of L0 and L1 penalty, such as the log penalty, is often needed for variable selection consistency. Thus, we develop a novel method that em-ploys log penalty within the framework of an earlier network identification method space (Sparse PArtial Correlation Estimation), and implement it into a R package space-log. We show that the space-log is computationally efficient (source code implemented in C), and has good performance comparing with other methods, particularly for networks with hubs.Space-log is open source and available at GitHub, https://github.com/wuqian77/SpaceLog

scholarly journals Space-log: a novel approach to inferring gene-gene net-works using SPACE model with log penalty

F1000Research ◽  
2020 ◽  
Vol 9 ◽  
pp. 1159
Author(s):  
Qian (Vicky) Wu ◽  
Wei Sun ◽  
Li Hsu
Keyword(s):  
Gene Expression ◽  
Gene Expression Data ◽  
Gene Networks ◽  
Regulatory Networks ◽  
Penalized Regression ◽  
R Package ◽  
Expression Data ◽  
Computationally Efficient ◽  
P Gene ◽  
Novel Approach

Gene expression data have been used to infer gene-gene networks (GGN) where an edge between two genes implies the conditional dependence of these two genes given all the other genes. Such gene-gene networks are of-ten referred to as gene regulatory networks since it may reveal expression regulation. Most of existing methods for identifying GGN employ penalized regression with L1 (lasso), L2 (ridge), or elastic net penalty, which spans the range of L1 to L2 penalty. However, for high dimensional gene expression data, a penalty that spans the range of L0 and L1 penalty, such as the log penalty, is often needed for variable selection consistency. Thus, we develop a novel method that em-ploys log penalty within the framework of an earlier network identification method space (Sparse PArtial Correlation Estimation), and implement it into a R package space-log. We show that the space-log is computationally efficient (source code implemented in C), and has good performance comparing with other methods, particularly for networks with hubs.Space-log is open source and available at GitHub, https://github.com/wuqian77/SpaceLog

scholarly journals iMIRAGE: an R package to impute microRNA expression using protein-coding genes

2019 ◽  
Vol 36 (8) ◽  
pp. 2608-2610
Author(s):  
Aritro Nath ◽  
Jeremy Chang ◽  
R Stephanie Huang
Keyword(s):  
Gene Expression ◽  
Small Rnas ◽  
Transcriptional Regulators ◽  
R Package ◽  
Machine Learning Algorithms ◽  
Supplementary Information ◽  
Expression Data ◽  
Protein Coding ◽  
Altered Protein ◽  
Independent Test

Abstract Summary MicroRNAs (miRNAs) are critical post-transcriptional regulators of gene expression. Due to challenges in accurate profiling of small RNAs, a vast majority of public transcriptome datasets lack reliable miRNA profiles. However, the biological consequence of miRNA activity in the form of altered protein-coding gene (PCG) expression can be captured using machine-learning algorithms. Here, we present iMIRAGE (imputed miRNA activity from gene expression), a convenient tool to predict miRNA expression using PCG expression of the test datasets. The iMIRAGE package provides an integrated workflow for normalization and transformation of miRNA and PCG expression data, along with the option to utilize predicted miRNA targets to impute miRNA activity from independent test PCG datasets. Availability and implementation The iMIRAGE package for R, along with package documentation and vignette, is available at https://aritronath.github.io/iMIRAGE/index.html. Supplementary information Supplementary data are available at Bioinformatics online.

scholarly journals Gene set enrichment for reproducible science: comparison of CERNO and eight other algorithms

2019 ◽  
Vol 35 (24) ◽  
pp. 5146-5154 ◽  
Author(s):  
Joanna Zyla ◽  
Michal Marczyk ◽  
Teresa Domaszewska ◽  
Stefan H E Kaufmann ◽  
Joanna Polanska ◽  
...  
Keyword(s):  
False Positive Rate ◽  
R Package ◽  
Supplementary Information ◽  
Computational Time ◽  
P Value ◽  
Gene Set ◽  
Related Data ◽  
Novel Approach ◽  
Positive Rate ◽  
Real World Datasets

Abstract Motivation Analysis of gene set (GS) enrichment is an essential part of functional omics studies. Here, we complement the established evaluation metrics of GS enrichment algorithms with a novel approach to assess the practical reproducibility of scientific results obtained from GS enrichment tests when applied to related data from different studies. Results We evaluated eight established and one novel algorithm for reproducibility, sensitivity, prioritization, false positive rate and computational time. In addition to eight established algorithms, we also included Coincident Extreme Ranks in Numerical Observations (CERNO), a flexible and fast algorithm based on modified Fisher P-value integration. Using real-world datasets, we demonstrate that CERNO is robust to ranking metrics, as well as sample and GS size. CERNO had the highest reproducibility while remaining sensitive, specific and fast. In the overall ranking Pathway Analysis with Down-weighting of Overlapping Genes, CERNO and over-representation analysis performed best, while CERNO and GeneSetTest scored high in terms of reproducibility. Availability and implementation tmod package implementing the CERNO algorithm is available from CRAN (cran.r-project.org/web/packages/tmod/index.html) and an online implementation can be found at http://tmod.online/. The datasets analyzed in this study are widely available in the KEGGdzPathwaysGEO, KEGGandMetacoreDzPathwaysGEO R package and GEO repository. Supplementary information Supplementary data are available at Bioinformatics online.

scholarly journals ABEMUS: platform-specific and data-informed detection of somatic SNVs in cfDNA

2020 ◽  
Vol 36 (9) ◽  
pp. 2665-2674
Author(s):  
Nicola Casiraghi ◽  
Francesco Orlando ◽  
Yari Ciani ◽  
Jenny Xiang ◽  
Andrea Sboner ◽  
...  
Keyword(s):  
Cancer Patients ◽  
R Package ◽  
Circulating Tumor Dna ◽  
Supplementary Information ◽  
Sequencing Error ◽  
Sequencing Data ◽  
Single Nucleotide Variants ◽  
Liquid Biopsies ◽  
Non Invasive ◽  
Cross Platform

Abstract Motivation The use of liquid biopsies for cancer patients enables the non-invasive tracking of treatment response and tumor dynamics through single or serial blood drawn tests. Next-generation sequencing assays allow for the simultaneous interrogation of extended sets of somatic single-nucleotide variants (SNVs) in circulating cell-free DNA (cfDNA), a mixture of DNA molecules originating both from normal and tumor tissue cells. However, low circulating tumor DNA (ctDNA) fractions together with sequencing background noise and potential tumor heterogeneity challenge the ability to confidently call SNVs. Results We present a computational methodology, called Adaptive Base Error Model in Ultra-deep Sequencing data (ABEMUS), which combines platform-specific genetic knowledge and empirical signal to readily detect and quantify somatic SNVs in cfDNA. We tested the capability of our method to analyze data generated using different platforms with distinct sequencing error properties and we compared ABEMUS performances with other popular SNV callers on both synthetic and real cancer patients sequencing data. Results show that ABEMUS performs better in most of the tested conditions proving its reliability in calling low variant allele frequencies somatic SNVs in low ctDNA levels plasma samples. Availability and implementation ABEMUS is cross-platform and can be installed as R package. The source code is maintained on Github at http://github.com/cibiobcg/abemus, and it is also available at CRAN official R repository. Supplementary information Supplementary data are available at Bioinformatics online.

scholarly journals DataRemix: a universal data transformation for optimal inference from gene expression datasets

2020 ◽  
Author(s):  
Weiguang Mao ◽  
Javad Rahimikollu ◽  
Ryan Hausler ◽  
Maria Chikina
Keyword(s):  
Gene Expression ◽  
R Package ◽  
Supplementary Information ◽  
Eqtl Analysis ◽  
Thompson Sampling ◽  
Normalization Methods ◽  
Special Cases ◽  
Biological Signals ◽  
Gene Correlation ◽  
Value Decomposition

Abstract Motivation RNA-seq technology provides unprecedented power in the assessment of the transcription abundance and can be used to perform a variety of downstream tasks such as inference of gene-correlation network and eQTL discovery. However, raw gene expression values have to be normalized for nuisance biological variation and technical covariates, and different normalization strategies can lead to dramatically different results in the downstream study. Results We describe a generalization of singular value decomposition-based reconstruction for which the common techniques of whitening, rank-k approximation and removing the top k principal components are special cases. Our simple three-parameter transformation, DataRemix, can be tuned to reweigh the contribution of hidden factors and reveal otherwise hidden biological signals. In particular, we demonstrate that the method can effectively prioritize biological signals over noise without leveraging external dataset-specific knowledge, and can outperform normalization methods that make explicit use of known technical factors. We also show that DataRemix can be efficiently optimized via Thompson sampling approach, which makes it feasible for computationally expensive objectives such as eQTL analysis. Finally, we apply our method to the Religious Orders Study and Memory and Aging Project dataset, and we report what to our knowledge is the first replicable trans-eQTL effect in human brain. Availabilityand implementation DataRemix is an R package which is freely available at GitHub (https://github.com/wgmao/DataRemix). Supplementary information Supplementary data are available at Bioinformatics online.

scholarly journals Integrating biological knowledge and gene expression data using pathway-guided random forests: a benchmarking study

2020 ◽  
Vol 36 (15) ◽  
pp. 4301-4308
Author(s):  
Stephan Seifert ◽  
Sven Gundlach ◽  
Olaf Junge ◽  
Silke Szymczak
Keyword(s):  
Gene Expression ◽  
Computational Models ◽  
Hybrid Approach ◽  
Disease Status ◽  
R Package ◽  
Gene Expression Omnibus ◽  
Functional Enrichment ◽  
Supplementary Information ◽  
Biological Knowledge ◽  
Functional Relationships

Abstract Motivation High-throughput technologies allow comprehensive characterization of individuals on many molecular levels. However, training computational models to predict disease status based on omics data is challenging. A promising solution is the integration of external knowledge about structural and functional relationships into the modeling process. We compared four published random forest-based approaches using two simulation studies and nine experimental datasets. Results The self-sufficient prediction error approach should be applied when large numbers of relevant pathways are expected. The competing methods hunting and learner of functional enrichment should be used when low numbers of relevant pathways are expected or the most strongly associated pathways are of interest. The hybrid approach synthetic features is not recommended because of its high false discovery rate. Availability and implementation An R package providing functions for data analysis and simulation is available at GitHub (https://github.com/szymczak-lab/PathwayGuidedRF). An accompanying R data package (https://github.com/szymczak-lab/DataPathwayGuidedRF) stores the processed and quality controlled experimental datasets downloaded from Gene Expression Omnibus (GEO). Supplementary information Supplementary data are available at Bioinformatics online.

scholarly journals ClusterMine: a Knowledge-integrated Clustering Approach based on Expression Profiles of Gene Sets

2018 ◽  
Author(s):  
Hong-Dong Li ◽  
Yunpei Xu ◽  
Xiaoshu Zhu ◽  
Quan Liu ◽  
Gilbert S. Omenn ◽  
...  
Keyword(s):  
Expression Profiles ◽  
R Package ◽  
Biological Data ◽  
Supplementary Information ◽  
Consensus Clustering ◽  
Cluster Membership ◽  
Link Type ◽  
Novel Approach ◽  
Gene Sets ◽  
Biological Interpretation

ABSTRACTMotivationClustering analysis is essential for understanding complex biological data. In widely used methods such as hierarchical clustering (HC) and consensus clustering (CC), expression profiles of all genes are often used to assess similarity between samples for clustering. These methods output sample clusters, but are not able to provide information about which gene sets (functions) contribute most to the clustering. So interpretability of their results is limited. We hypothesized that integrating prior knowledge of annotated biological processes would not only achieve satisfying clustering performance but also, more importantly, enable potential biological interpretation of clusters.ResultsHere we report ClusterMine, a novel approach that identifies clusters by assessing functional similarity between samples through integrating known annotated gene sets, e.g., in Gene Ontology. In addition to outputting cluster membership of each sample as conventional approaches do, it outputs gene sets that are most likely to contribute to the clustering, a feature facilitating biological interpretation. Using three cancer datasets, two single cell RNA-sequencing based cell differentiation datasets, one cell cycle dataset and two datasets of cells of different tissue origins, we found that ClusterMine achieved similar or better clustering performance and that top-scored gene sets prioritized by ClusterMine are biologically relevant.Implementation and availabilityClusterMine is implemented as an R package and is freely available at: www.genemine.org/[email protected] InformationSupplementary data are available at Bioinformatics online.

MGIDI: toward an effective multivariate selection in biological experiments

2020 ◽  
Author(s):  
Tiago Olivoto ◽  
Maicon Nardino
Keyword(s):  
High Performance ◽  
Selection Process ◽  
A Priori ◽  
R Package ◽  
Supplementary Information ◽  
Treatment Recommendation ◽  
Multiple Traits ◽  
Monte Carlo Simulation Study ◽  
Novel Approach ◽  
Weighting Coefficients

Abstract Motivation Multivariate data are common in biological experiments and using the information on multiple traits is crucial to make better decisions for treatment recommendations or genotype selection. However, identifying genotypes/treatments that combine high performance across many traits has been a challenger task. Classical linear multi-trait selection indexes are available, but the presence of multicollinearity and the arbitrary choosing of weighting coefficients may erode the genetic gains. Results We propose a novel approach for genotype selection and treatment recommendation based on multiple traits that overcome the fragility of classical linear indexes. Here, we use the distance between the genotypes/treatment with an ideotype defined a priori as a multi-trait genotype–ideotype distance index (MGIDI) to provide a selection process that is unique, easy-to-interpret, free from weighting coefficients and multicollinearity issues. The performance of the MGIDI index is assessed through a Monte Carlo simulation study where the percentage of success in selecting traits with desired gains is compared with classical and modern indexes under different scenarios. Two real plant datasets are used to illustrate the application of the index from breeders and agronomists’ points of view. Our experimental results indicate that MGIDI can effectively select superior treatments/genotypes based on multi-trait data, outperforming state-of-the-art methods, and helping practitioners to make better strategic decisions toward an effective multivariate selection in biological experiments. Availability and implementation The source code is available in the R package metan (https://github.com/TiagoOlivoto/metan) under the function mgidi(). Supplementary information Supplementary data are available at Bioinformatics online.

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