Find open-source science resources

Model-based analysis of single-cell methylation data

BiFET identifies TFs whose footprints are over-represented in target regions compared to background regions after correcting for the bias arising from the imbalance in read counts and GC contents between the target and background regions. For a given TF k, BiFET tests the null hypothesis that the target regions have the same probability of having footprints for the TF k as the background regions while correcting for the read count and GC content bias. For this, we use the number of target regions with footprints for TF k, t_k as a test statistic and calculate the p-value as the probability of observing t_k or more target regions with footprints under the null hypothesis.

bioassayR is a computational tool that enables simultaneous analysis of thousands of bioassay experiments performed over a diverse set of compounds and biological targets. Unique features include support for large-scale cross-target analyses of both public and custom bioassays, generation of high throughput screening fingerprints (HTSFPs), and an optional preloaded database that provides access to a substantial portion of publicly available bioactivity data.

Wraps common clustering algorithms in an easily extended S4 framework. Backends are implemented for hierarchical, k-means and graph-based clustering. Several utilities are also provided to compare and evaluate clustering results.

Package for calculating aggregated isotopic distribution and exact center-masses for chemical substances (in this version composed of C, H, N, O and S). This is an implementation of the BRAIN algorithm described in the paper by J. Claesen, P. Dittwald, T. Burzykowski and D. Valkenborg.

This is a probabilistic modelling pipeline for computing per- nucleotide posterior probabilities of modification from the data collected in structure probing experiments. The model supports multiple experimental replicates and empirically corrects coverage- and sequence-dependent biases. The model utilises the measure of a "drop-off rate" for each nucleotide, which is compared between replicates through a log-ratio (LDR). The LDRs between control replicates define a null distribution of variability in drop-off rate observed by chance and LDRs between treatment and control replicates gets compared to this distribution. Resulting empirical p-values (probability of being "drawn" from the null distribution) are used as observations in a Hidden Markov Model with a Beta-Uniform Mixture model used as an emission model. The resulting posterior probabilities indicate the probability of a nucleotide of having being modified in a structure probing experiment.

Annotation of peaklists generated by xcms, rule based annotation of isotopes and adducts, isotope validation, EIC correlation based tagging of unknown adducts and fragments

Infer alternative splicing from paired-end RNA-seq data. The model is based on counting paths across exons, rather than pairwise exon connections, and estimates the fragment size and start distributions non-parametrically, which improves estimation precision.

Causal network analysis methods for regulator prediction and network reconstruction from genome scale data.

This R package provides an R Shiny application that enables the user to generate, manage, and edit data and metadata files suitable for the import in cBioPortal for Cancer Genomics. Create cancer studies and edit its metadata. Upload mutation data of a patient that will be concatenated to the data_mutation_extended.txt file of the study. Create and edit clinical patient data, sample data, and timeline data. Create custom timeline tracks for patients.

The CCREPE (Compositionality Corrected by REnormalizaion and PErmutation) package is designed to assess the significance of general similarity measures in compositional datasets. In microbial abundance data, for example, the total abundances of all microbes sum to one; CCREPE is designed to take this constraint into account when assigning p-values to similarity measures between the microbes. The package has two functions: ccrepe: Calculates similarity measures, p-values and q-values for relative abundances of bugs in one or two body sites using bootstrap and permutation matrices of the data. nc.score: Calculates species-level co-variation and co-exclusion patterns based on an extension of the checkerboard score to ordinal data.

A support vector machine approach to identifying and filtering low quality cells from single-cell RNA-seq datasets.

CellTrails is an unsupervised algorithm for the de novo chronological ordering, visualization and analysis of single-cell expression data. CellTrails makes use of a geometrically motivated concept of lower-dimensional manifold learning, which exhibits a multitude of virtues that counteract intrinsic noise of single cell data caused by drop-outs, technical variance, and redundancy of predictive variables. CellTrails enables the reconstruction of branching trajectories and provides an intuitive graphical representation of expression patterns along all branches simultaneously. It allows the user to define and infer the expression dynamics of individual and multiple pathways towards distinct phenotypes.

ChIP-Enrich and Poly-Enrich perform gene set enrichment testing using peaks called from a ChIP-seq experiment. The method empirically corrects for confounding factors such as the length of genes, and the mappability of the sequence surrounding genes.

This add-on to the package CellNOptR handles time-course data, as opposed to steady state data in CellNOptR. It scales the simulation step to allow comparison and model fitting for time-course data. Future versions will optimize delays and strengths for each edge.

Logic based ordinary differential equation (ODE) add-on to CellNOptR.

A normalization and copy number variation calling procedure for whole exome DNA sequencing data. CODEX relies on the availability of multiple samples processed using the same sequencing pipeline for normalization, and does not require matched controls. The normalization model in CODEX includes terms that specifically remove biases due to GC content, exon length and targeting and amplification efficiency, and latent systemic artifacts. CODEX also includes a Poisson likelihood-based recursive segmentation procedure that explicitly models the count-based exome sequencing data.

COMPASS is a statistical framework that enables unbiased analysis of antigen-specific T-cell subsets. COMPASS uses a Bayesian hierarchical framework to model all observed cell-subsets and select the most likely to be antigen-specific while regularizing the small cell counts that often arise in multi-parameter space. The model provides a posterior probability of specificity for each cell subset and each sample, which can be used to profile a subject's immune response to external stimuli such as infection or vaccination.

Single Cell Fluidigm Spot Detector.

cosmiq is a tool for the preprocessing of liquid- or gas - chromatography mass spectrometry (LCMS/GCMS) data with a focus on metabolomics or lipidomics applications. To improve the detection of low abundant signals, cosmiq generates master maps of the mZ/RT space from all acquired runs before a peak detection algorithm is applied. The result is a more robust identification and quantification of low-intensity MS signals compared to conventional approaches where peak picking is performed in each LCMS/GCMS file separately. The cosmiq package builds on the xcmsSet object structure and can be therefore integrated well with the package xcms as an alternative preprocessing step.

Using bayesian methods to estimate correlation matrices assuming that they can be written and estimated as block diagonal matrices. These block diagonal matrices are determined using shrinkage parameters that values below this parameter to zero.

This package provides a framework for the visualization of genome coverage profiles. It can be used for ChIP-seq experiments, but it can be also used for genome-wide nucleosome positioning experiments or other experiment types where it is important to have a framework in order to inspect how the coverage distributed across the genome

A normalization tool for RNA-Seq data, implementing the conditional quantile normalization method.

The package encompasses functions to find potential guide RNAs for the CRISPR-based genome-editing systems including the Base Editors and the Prime Editors when supplied with target sequences as input. Users have the flexibility to filter resulting guide RNAs based on parameters such as the absence of restriction enzyme cut sites or the lack of paired guide RNAs. The package also facilitates genome-wide exploration for off-targets, offering features to score and rank off-targets, retrieve flanking sequences, and indicate whether the hits are located within exon regions. All detected guide RNAs are annotated with the cumulative scores of the top5 and topN off-targets together with the detailed information such as mismatch sites and restrictuion enzyme cut sites. The package also outputs INDELs and their frequencies for Cas9 targeted sites.

CrispRVariants provides tools for analysing the results of a CRISPR-Cas9 mutagenesis sequencing experiment, or other sequencing experiments where variants within a given region are of interest. These tools allow users to localize variant allele combinations with respect to any genomic location (e.g. the Cas9 cut site), plot allele combinations and calculate mutation rates with flexible filtering of unrelated variants.

Database search is the most widely used approach for peptide and protein identification in mass spectrometry-based proteomics studies. Our previous study showed that sample-specific protein databases derived from RNA-Seq data can better approximate the real protein pools in the samples and thus improve protein identification. More importantly, single nucleotide variations, short insertion and deletions and novel junctions identified from RNA-Seq data make protein database more complete and sample-specific. Here, we report an R package customProDB that enables the easy generation of customized databases from RNA-Seq data for proteomics search. This work bridges genomics and proteomics studies and facilitates cross-omics data integration.

Identifies differentially abundant populations between samples and groups in mass cytometry data. Provides methods for counting cells into hyperspheres, controlling the spatial false discovery rate, and visualizing changes in abundance in the high-dimensional marker space.

This package provides functions that predict clinical outcomes using single cell data (such as flow cytometry data, RNA single cell sequencing data) without the requirement of cell gating or clustering.

cytoKernel implements a kernel-based score test to identify differentially expressed features in high-dimensional biological experiments. This approach can be applied across many different high-dimensional biological data including gene expression data and dimensionally reduced cytometry-based marker expression data. In this R package, we implement functions that compute the feature-wise p values and their corresponding adjusted p values. Additionally, it also computes the feature-wise shrunk effect sizes and their corresponding shrunken effect size. Further, it calculates the percent of differentially expressed features and plots user-friendly heatmap of the top differentially expressed features on the rows and samples on the columns.

This package provides the core data structure and API to represent and interact with the gated cytometry data.

The dada2 package infers exact amplicon sequence variants (ASVs) from high-throughput amplicon sequencing data, replacing the coarser and less accurate OTU clustering approach. The dada2 pipeline takes as input demultiplexed fastq files, and outputs the sequence variants and their sample-wise abundances after removing substitution and chimera errors. Taxonomic classification is available via a native implementation of the RDP naive Bayesian classifier, and species-level assignment to 16S rRNA gene fragments by exact matching.

Distance-correlation based Gene Set Analysis for longitudinal gene expression profiles. In longitudinal studies, the gene expression profiles were collected at each visit from each subject and hence there are multiple measurements of the gene expression profiles for each subject. The dcGSA package could be used to assess the associations between gene sets and clinical outcomes of interest by fully taking advantage of the longitudinal nature of both the gene expression profiles and clinical outcomes.

Simple statistical identification of contaminating sequence features in marker-gene or metagenomics data. Works on any kind of feature derived from environmental sequencing data (e.g. ASVs, OTUs, taxonomic groups, MAGs,...). Requires DNA quantitation data or sequenced negative control samples.

DEqMS is developped on top of Limma. However, Limma assumes same prior variance for all genes. In proteomics, the accuracy of protein abundance estimates varies by the number of peptides/PSMs quantified in both label-free and labelled data. Proteins quantification by multiple peptides or PSMs are more accurate. DEqMS package is able to estimate different prior variances for proteins quantified by different number of PSMs/peptides, therefore acchieving better accuracy. The package can be applied to analyze both label-free and labelled proteomics data.

Integrated peak and differential caller, specifically designed for broad epigenomic signals.

The package is focused on finding differential exon usage using RNA-seq exon counts between samples with different experimental designs. It provides functions that allows the user to make the necessary statistical tests based on a model that uses the negative binomial distribution to estimate the variance between biological replicates and generalized linear models for testing. The package also provides functions for the visualization and exploration of the results.

Statistical methods for differential discovery analyses in high-dimensional cytometry data (including flow cytometry, mass cytometry or CyTOF, and oligonucleotide-tagged cytometry), based on a combination of high-resolution clustering and empirical Bayes moderated tests adapted from transcriptomics.

Dirichlet-multinomial mixture models can be used to describe variability in microbial metagenomic data. This package is an interface to code originally made available by Holmes, Harris, and Quince, 2012, PLoS ONE 7(2): 1-15, as discussed further in the man page for this package, ?DirichletMultinomial.

Discordant is an R package that identifies pairs of features that correlate differently between phenotypic groups, with application to -omics data sets. Discordant uses a mixture model that “bins” molecular feature pairs based on their type of coexpression or coabbundance. Algorithm is explained further in "Differential Correlation for Sequencing Data"" (Siska et al. 2016).

This package implements an approach for scanning the genome to detect and perform accurate inference on differentially methylated regions from Whole Genome Bisulfite Sequencing data. The method is based on comparing detected regions to a pooled null distribution, that can be implemented even when as few as two samples per population are available. Region-level statistics are obtained by fitting a generalized least squares (GLS) regression model with a nested autoregressive correlated error structure for the effect of interest on transformed methylation proportions.

The package provides two frameworks. One for the differential transcript usage analysis between different conditions and one for the tuQTL analysis. Both are based on modeling the counts of genomic features (i.e., transcripts) with the Dirichlet-multinomial distribution. The package also makes available functions for visualization and exploration of the data and results.

Provides a number of utility functions for handling single-cell (RNA-seq) data from droplet technologies such as 10X Genomics. This includes data loading from count matrices or molecule information files, identification of cells from empty droplets, removal of barcode-swapped pseudo-cells, and downsampling of the count matrix.

Differential Expression analysis at both gene and isoform level using RNA-seq data

Numerical and graphical summaries of RNA-Seq read data. Within-lane normalization procedures to adjust for GC-content effect (or other gene-level effects) on read counts: loess robust local regression, global-scaling, and full-quantile normalization (Risso et al., 2011). Between-lane normalization procedures to adjust for distributional differences between lanes (e.g., sequencing depth): global-scaling and full-quantile normalization (Bullard et al., 2010).

This package implements the Ensemble of Gene Set Enrichment Analyses (EGSEA) method for gene set testing. EGSEA algorithm utilizes the analysis results of twelve prominent GSE algorithms in the literature to calculate collective significance scores for each gene set.

The EnrichmentBrowser package implements essential functionality for the enrichment analysis of gene expression data. The analysis combines the advantages of set-based and network-based enrichment analysis in order to derive high-confidence gene sets and biological pathways that are differentially regulated in the expression data under investigation. Besides, the package facilitates the visualization and exploration of such sets and pathways.

Technical performance metrics for differential gene expression experiments using External RNA Controls Consortium (ERCC) spike-in ratio mixtures.

The ERSSA package takes user supplied RNA-seq differential expression dataset and calculates the number of differentially expressed genes at varying biological replicate levels. This allows the user to determine, without relying on any a priori assumptions, whether sufficient differential detection has been acheived with their RNA-seq dataset.

This package provides a framework and complete preset pipeline for quantification and analysis of ATAC-seq Reads. It covers raw sequencing reads preprocessing (FASTQ files), reads alignment (Rbowtie2), aligned reads file operations (SAM, BAM, and BED files), peak calling (F-seq), genome annotations (Motif, GO, SNP analysis) and quality control report. The package is managed by dataflow graph. It is easy for user to pass variables seamlessly between processes and understand the workflow. Users can process FASTQ files through end-to-end preset pipeline which produces a pretty HTML report for quality control and preliminary statistical results, or customize workflow starting from any intermediate stages with esATAC functions easily and flexibly.

ExCluster flattens Ensembl and GENCODE GTF files into GFF files, which are used to count reads per non-overlapping exon bin from BAM files. This read counting is done using the function featureCounts from the package Rsubread. Library sizes are normalized across all biological replicates, and ExCluster then compares two different conditions to detect signifcantly differentially spliced genes. This process requires at least two independent biological repliates per condition, and ExCluster accepts only exactly two conditions at a time. ExCluster ultimately produces false discovery rates (FDRs) per gene, which are used to detect significance. Exon log2 fold change (log2FC) means and variances may be plotted for each significantly differentially spliced gene, which helps scientists develop hypothesis and target differential splicing events for RT-qPCR validation in the wet lab.