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Contains a set of functions to perform large-scale analysis of pharmaco-genomic data. These include the PharmacoSet object for storing the results of pharmacogenomic experiments, as well as a number of functions for computing common summaries of drug-dose response and correlating them with the molecular features in a cancer cell-line.

PhantasusLite – a lightweight package with helper functions of general interest extracted from phantasus package. In parituclar it simplifies working with public RNA-seq datasets from GEO by providing access to the remote HSDS repository with the precomputed gene counts from ARCHS4 and DEE2 projects.

Pancreatic ductal adenocarcinoma (PDA) has a relatively poor prognosis and is one of the most lethal cancers. Molecular classification of gene expression profiles holds the potential to identify meaningful subtypes which can inform therapeutic strategy in the clinical setting. The Pancreatic Cancer Adenocarcinoma Tool-Kit (PDATK) provides an S4 class-based interface for performing unsupervised subtype discovery, cross-cohort meta-clustering, gene-expression-based classification, and subsequent survival analysis to identify prognostically useful subtypes in pancreatic cancer and beyond. Two novel methods, Consensus Subtypes in Pancreatic Cancer (CSPC) and Pancreatic Cancer Overall Survival Predictor (PCOSP) are included for consensus-based meta-clustering and overall-survival prediction, respectively. Additionally, four published subtype classifiers and three published prognostic gene signatures are included to allow users to easily recreate published results, apply existing classifiers to new data, and benchmark the relative performance of new methods. The use of existing Bioconductor classes as input to all PDATK classes and methods enables integration with existing Bioconductor datasets, including the 21 pancreatic cancer patient cohorts available in the MetaGxPancreas data package. PDATK has been used to replicate results from Sandhu et al (2019) [https://doi.org/10.1200/cci.18.00102] and an additional paper is in the works using CSPC to validate subtypes from the included published classifiers, both of which use the data available in MetaGxPancreas. The inclusion of subtype centroids and prognostic gene signatures from these and other publications will enable researchers and clinicians to classify novel patient gene expression data, allowing the direct clinical application of the classifiers included in PDATK. Overall, PDATK provides a rich set of tools to identify and validate useful prognostic and molecular subtypes based on gene-expression data, benchmark new classifiers against existing ones, and apply discovered classifiers on novel patient data to inform clinical decision making.

PanomiR is a package to detect miRNAs that target groups of pathways from gene expression data. This package provides functionality for generating pathway activity profiles, determining differentially activated pathways between user-specified conditions, determining clusters of pathways via the PCxN package, and generating miRNAs targeting clusters of pathways. These function can be used separately or sequentially to analyze RNA-Seq data.

This package translates microarray expression data into metadata of reduced dimension. It provides various sample-centered and group-centered visualizations, sample similarity analyses and functional enrichment analyses. The underlying SOM algorithm combines feature clustering, multidimensional scaling and dimension reduction, along with strong visualization capabilities. It enables extraction and description of functional expression modules inherent in the data.

This package helps identify mRNAs that are overexpressed in subsets of tumors relative to normal tissue. Ideal inputs would be paired tumor-normal data from the same tissue from many patients (>15 pairs). This unsupervised approach relies on the observation that oncogenes are characteristically overexpressed in only a subset of tumors in the population, and may help identify oncogene candidates purely based on differences in mRNA expression between previously unknown subtypes.

Tools for NanoString Technologies nCounter Technology. Provides support for reading RCC files into an ExpressionSet derived object. Also includes methods for QC and normalizaztion of NanoString data.

This package provide a method for doing gene set analysis based on multiple omics data.

MODA can be used to estimate and construct condition-specific gene co-expression networks, and identify differentially expressed subnetworks as conserved or condition specific modules which are potentially associated with relevant biological processes.

mitology allows to study the mitochondrial activity throught high-throughput RNA-seq data. It is based on a collection of genes whose proteins localize in to the mitochondria. From these, mitology provides a reorganization of the pathways related to mitochondria activity from Reactome and Gene Ontology. Further a ready-to-use implementation of MitoCarta3.0 pathways is included.

mitch is an R package for multi-contrast enrichment analysis. At it’s heart, it uses a rank-MANOVA based statistical approach to detect sets of genes that exhibit enrichment in the multidimensional space as compared to the background. The rank-MANOVA concept dates to work by Cox and Mann (https://doi.org/10.1186/1471-2105-13-S16-S12). mitch is useful for pathway analysis of profiling studies with one, two or more contrasts, or in studies with multiple omics profiling, for example proteomic, transcriptomic, epigenomic analysis of the same samples. mitch is perfectly suited for pathway level differential analysis of scRNA-seq data. We have an established routine for pathway enrichment of Infinium Methylation Array data (see vignette). The main strengths of mitch are that it can import datasets easily from many upstream tools and has advanced plotting features to visualise these enrichments.

This package provides several functions to explore miRNA sponge (also called ceRNA or miRNA decoy) regulation from putative miRNA-target interactions or/and transcriptomics data (including bulk, single-cell and spatial gene expression data). It provides eight popular methods for identifying miRNA sponge interactions, and an integrative method to integrate miRNA sponge interactions from different methods, as well as the functions to validate miRNA sponge interactions, and infer miRNA sponge modules, conduct enrichment analysis of miRNA sponge modules, and conduct survival analysis of miRNA sponge modules. By using a sample control variable strategy, it provides a function to infer sample-specific miRNA sponge interactions. In terms of sample-specific miRNA sponge interactions, it implements three similarity methods to construct sample-sample correlation network.

The package aims to identify miRNA sponge or ceRNA modules in heterogeneous data. It provides several functions to study miRNA sponge modules at single-sample and multi-sample levels, including popular methods for inferring gene modules (candidate miRNA sponge or ceRNA modules), and two functions to identify miRNA sponge modules at single-sample and multi-sample levels, as well as several functions to conduct modular analysis of miRNA sponge modules.

Our pipeline, MICSQTL, utilizes scRNA-seq reference and bulk transcriptomes to estimate cellular composition in the matched bulk proteomes. The expression of genes and proteins at either bulk level or cell type level can be integrated by Angle-based Joint and Individual Variation Explained (AJIVE) framework. Meanwhile, MICSQTL can perform cell-type-specic quantitative trait loci (QTL) mapping to proteins or transcripts based on the input of bulk expression data and the estimated cellular composition per molecule type, without the need for single cell sequencing. We use matched transcriptome-proteome from human brain frontal cortex tissue samples to demonstrate the input and output of our tool.

Messina is a collection of algorithms for constructing optimally robust single-gene classifiers, and for identifying differential expression in the presence of outliers or unknown sample subgroups. The methods have application in identifying lead features to develop into clinical tests (both diagnostic and prognostic), and in identifying differential expression when a fraction of samples show unusual patterns of expression.

Methods and models for handling zero-inflated single cell assay data.

The tool integrates data from biological networks with transcriptomes, displaying a heatmap with surface curves to evidence the altered regions.

KnowSeq proposes a novel methodology that comprises the most relevant steps in the Transcriptomic gene expression analysis. KnowSeq expects to serve as an integrative tool that allows to process and extract relevant biomarkers, as well as to assess them through a Machine Learning approaches. Finally, the last objective of KnowSeq is the biological knowledge extraction from the biomarkers (Gene Ontology enrichment, Pathway listing and Visualization and Evidences related to the addressed disease). Although the package allows analyzing all the data manually, the main strenght of KnowSeq is the possibilty of carrying out an automatic and intelligent HTML report that collect all the involved steps in one document. It is important to highligh that the pipeline is totally modular and flexible, hence it can be started from whichever of the different steps. KnowSeq expects to serve as a novel tool to help to the experts in the field to acquire robust knowledge and conclusions for the data and diseases to study.

Analysis of alternative splicing and isoform switches with predicted functional consequences (e.g. gain/loss of protein domains etc.) from quantification of all types of RNA-seq (short/long) by tools such as Kallisto, Salmon, StringTie, Tallon, IsoQuant etc.

This package consolidates a comprehensive set of information measurements, encompassing mutual information, conditional mutual information, interaction information, partial information decomposition, and part mutual information.

The iNETgrate package provides functions to build a correlation network in which nodes are genes. DNA methylation and gene expression data are integrated to define the connections between genes. This network is used to identify modules (clusters) of genes. The biological information in each of the resulting modules is represented by an eigengene. These biological signatures can be used as features e.g., for classification of patients into risk categories. The resulting biological signatures are very robust and give a holistic view of the underlying molecular changes.

QC pipeline and data analysis tools for high-dimensional Illumina mRNA expression data.

Performs hybrid multiple testing that incorporates method selection and assumption evaluations into the analysis using empirical Bayes probability (EBP) estimates obtained by Grenander density estimation. For instance, for 3-group comparison analysis, Hybrid Multiple testing considers EBPs as weighted EBPs between F-test and H-test with EBPs from Shapiro Wilk test of normality as weigth. Instead of just using EBPs from F-test only or using H-test only, this methodology combines both types of EBPs through EBPs from Shapiro Wilk test of normality. This methodology uses then the law of total EBPs.

A multi-objective optimization algorithm for disease sub-type discovery based on a non-dominated sorting genetic algorithm. The 'Galgo' framework combines the advantages of clustering algorithms for grouping heterogeneous 'omics' data and the searching properties of genetic algorithms for feature selection. The algorithm search for the optimal number of clusters determination considering the features that maximize the survival difference between sub-types while keeping cluster consistency high.

This package provides classes and methods to support Gene Set Enrichment Analysis (GSEA).

GSCA takes as input several lists of activated and repressed genes. GSCA then searches through a compendium of publicly available gene expression profiles for biological contexts that are enriched with a specified pattern of gene expression. GSCA provides both traditional R functions and interactive, user-friendly user interface.

Gene lists derived from the results of genomic analyses are rich in biological information. For instance, differentially expressed genes (DEGs) from a microarray or RNA-Seq analysis are related functionally in terms of their response to a treatment or condition. Gene lists can vary in size, up to several thousand genes, depending on the robustness of the perturbations or how widely different the conditions are biologically. Having a way to associate biological relatedness between hundreds and thousands of genes systematically is impractical by manually curating the annotation and function of each gene. Over-representation analysis (ORA) of genes was developed to identify biological themes. Given a Gene Ontology (GO) and an annotation of genes that indicate the categories each one fits into, significance of the over-representation of the genes within the ontological categories is determined by a Fisher's exact test or modeling according to a hypergeometric distribution. Comparing a small number of enriched biological categories for a few samples is manageable using Venn diagrams or other means for assessing overlaps. However, with hundreds of enriched categories and many samples, the comparisons are laborious. Furthermore, if there are enriched categories that are shared between samples, trying to represent a common theme across them is highly subjective. goSTAG uses GO subtrees to tag and annotate genes within a set. goSTAG visualizes the similarities between the over-representation of DEGs by clustering the p-values from the enrichment statistical tests and labels clusters with the GO term that has the most paths to the root within the subtree generated from all the GO terms in the cluster.

Cluster genes to functional groups with E-M process. Iteratively perform TF assigning and Gene assigning, until the assignment of genes did not change, or max number of iterations is reached.

The method may be conceptualised as a test of overall significance in regression analysis, where the response variable is overdispersed and the number of explanatory variables exceeds the sample size. Useful for testing for association between RNA-Seq and high-dimensional data.

gINTomics is an R package for Multi-Omics data integration and visualization. gINTomics is designed to detect the association between the expression of a target and of its regulators, taking into account also their genomics modifications such as Copy Number Variations (CNV) and methylation. What is more, gINTomics allows integration results visualization via a Shiny-based interactive app.

Digital Expression Explorer 2 (or DEE2 for short) is a repository of processed RNA-seq data in the form of counts. It was designed so that researchers could undertake re-analysis and meta-analysis of published RNA-seq studies quickly and easily. As of April 2020, over 1 million SRA datasets have been processed. This package provides an R interface to access these expression data. More information about the DEE2 project can be found at the project homepage (http://dee2.io) and main publication (https://doi.org/10.1093/gigascience/giz022).

Pathway Expression Profiles (PEPs) are based on the expression of pathways (defined as sets of genes) as opposed to individual genes. This package converts gene expression profiles to PEPs and performs enrichment analysis of both pathways and experimental conditions, such as "drug set enrichment analysis" and "gene2drug" drug discovery analysis respectively.

Gene Expression Omnibus(GEO) and The Cancer Genome Atlas (TCGA) provide us with a wealth of data, such as RNA-seq, DNA Methylation, SNP and Copy number variation data. It's easy to download data from TCGA using the gdc tool, but processing these data into a format suitable for bioinformatics analysis requires more work. This R package was developed to handle these data.

Tools for NanoString Technologies GeoMx Technology. Package provides functions for reading in DCC and PKC files based on an ExpressionSet derived object. Normalization and QC functions are also included.

A series of statistical models using count generating distributions for background modelling, feature and sample QC, normalization and differential expression analysis on GeoMx RNA data. The application of these methods are demonstrated by example data analysis vignette.

R based Genetic algorithm for gene expression optimization by considering both mRNA secondary structure and codon usage bias, GeneGA includes the information of highly expressed genes of almost 200 genomes. Meanwhile, Vienna RNA Package is needed to ensure GeneGA to function properly.

This packages aims for easy accessible application of classifiers which have been published in literature using an ExpressionSet as input.

This package implements a metabolic network analysis pipeline to identify an active metabolic module based on high throughput data. The pipeline takes as input transcriptional and/or metabolic data and finds a metabolic subnetwork (module) most regulated between the two conditions of interest. The package further provides functions for module post-processing, annotation and visualization.

The package implements an algorithm for fast gene set enrichment analysis. Using the fast algorithm allows to make more permutations and get more fine grained p-values, which allows to use accurate stantard approaches to multiple hypothesis correction.

Used to determine which cell types are enriched within gene lists. The package provides tools for testing enrichments within simple gene lists (such as human disease associated genes) and those resulting from differential expression studies. The package does not depend upon any particular Single Cell Transcriptome dataset and user defined datasets can be loaded in and used in the analyses.

Calculates the coverage of high-throughput short-reads against a genome of reference and summarizes it per feature of interest (e.g. exon, gene, transcript). The data can be normalized as 'RPKM' or by the 'DESeq' or 'edgeR' package.

This package provides a workflow for the use of EaSIeR tool, developed to assess patients' likelihood to respond to ICB therapies providing just the patients' RNA-seq data as input. We integrate RNA-seq data with different types of prior knowledge to extract quantitative descriptors of the tumor microenvironment from several points of view, including composition of the immune repertoire, and activity of intra- and extra-cellular communications. Then, we use multi-task machine learning trained in TCGA data to identify how these descriptors can simultaneously predict several state-of-the-art hallmarks of anti-cancer immune response. In this way we derive cancer-specific models and identify cancer-specific systems biomarkers of immune response. These biomarkers have been experimentally validated in the literature and the performance of EaSIeR predictions has been validated using independent datasets form four different cancer types with patients treated with anti-PD1 or anti-PDL1 therapy.

The diffUTR package provides a uniform interface and plotting functions for limma/edgeR/DEXSeq -powered differential bin/exon usage. It includes in addition an improved version of the limma::diffSplice method. Most importantly, diffUTR further extends the application of these frameworks to differential UTR usage analysis using poly-A site databases.

A tool for the identification of differentially coexpressed links (DCLs) and differentially coexpressed genes (DCGs). DCLs are gene pairs with significantly different correlation coefficients under two conditions. DCGs are genes with significantly more DCLs than by chance.

The goal of DELocal is to identify DE genes compared to their neighboring genes from the same chromosomal location. It has been shown that genes of related functions are generally very far from each other in the chromosome. DELocal utilzes this information to identify DE genes comparing with their neighbouring genes.

DegCre generates associations between differentially expressed genes (DEGs) and cis-regulatory elements (CREs) based on non-parametric concordance between differential data. The user provides GRanges of DEG TSS and CRE regions with differential p-value and optionally log-fold changes and DegCre returns an annotated Hits object with associations and their calculated probabilities. Additionally, the package provides functionality for visualization and conversion to other formats.

The Delta-Delta-Ct (ddCt) Algorithm is an approximation method to determine relative gene expression with quantitative real-time PCR (qRT-PCR) experiments. Compared to other approaches, it requires no standard curve for each primer-target pair, therefore reducing the working load and yet returning accurate enough results as long as the assumptions of the amplification efficiency hold. The ddCt package implements a pipeline to collect, analyse and visualize qRT-PCR results, for example those from TaqMan SDM software, mainly using the ddCt method. The pipeline can be either invoked by a script in command-line or through the API consisting of S4-Classes, methods and functions.

Denoising Algorithm based on Relevance network Topology (DART) is an algorithm designed to evaluate the consistency of prior information molecular signatures (e.g in-vitro perturbation expression signatures) in independent molecular data (e.g gene expression data sets). If consistent, a pruning network strategy is then used to infer the activation status of the molecular signature in individual samples.

The R package CTSV implements the CTSV approach developed by Jinge Yu and Xiangyu Luo that detects cell-type-specific spatially variable genes accounting for excess zeros. CTSV directly models sparse raw count data through a zero-inflated negative binomial regression model, incorporates cell-type proportions, and performs hypothesis testing based on R package pscl. The package outputs p-values and q-values for genes in each cell type, and CTSV is scalable to datasets with tens of thousands of genes measured on hundreds of spots. CTSV can be installed in Windows, Linux, and Mac OS.

This package provides the analysis methods fourthcorner and RLQ analysis for large-scale transcriptomic data.