alussana / affixcan

A functional approach to estimate GReX - genetically regulated expression

AffiXcan

AffiXcan is an R package that includes a set of functions to train and to apply statistical models to estimate the GReX (genetically regulated expression).

To use AffiXcan please refer to the Bioconductor webpage.

Background

Understanding and predicting how genetic variation influences gene expression in cells and tissues is of great interest in modern biological and medical sciences.

The present methods to estimate the genetic contribution to gene expression do not take into account functional information in identifying expression quantitative trait loci (eQTL), i.e. those genetic variants that contribute to explaining the variation of gene expression. Relying on SNPs as predictors allows to make significant models of gene expression only for those genes for which SNPs with a fairly good effect size exist, but this condition is not satisfied for the majority of genes, despite their expression having a non-zero heritability (h²). To address this issue, new, different strategies to analyze genetic variability of regulatory regions and their influence on transcription are needed.

General features

AffiXcan (total binding AFFInity-eXpression sCANner) implements a functional approach based on the TBA (Total Binding Affinity) score to make statistical models of gene expression, being able to make significant predictions on genes for which SNPs with strong effect size are absent. Furthermore, such a functional approach allows to make mechanistic interpretations in terms of transcription factors binding events that drive differential transcriptional expression. These features are of considerable importance for eQTL discovery and to improve the capability to estimate a GReX (genetically regulated expression) for a greater number of genes, at the same time giving insights on the possible molecular mechanisms that are involved in differential expression of genes.

affixcan's Issues

Changes to ExperimentList interface

Ciao Alessandro, @alussana

I'm making changes to the ExperimentList interface to support MultiAssayExperiment-like
subsetting. I've run r-libs/revdepcheck on MultiAssayExperiment and your package seems
to fail with the new changes.

Please see this branch for the changes: https://github.com/waldronlab/MultiAssayExperiment/tree/expsubset

revdepcheck results

# AffiXcan

* Version: 1.7.0
* GitHub: NA
* Source code: https://github.com/alussana/AffiXcan
* Date/Publication: 2020-04-27
* Number of recursive dependencies: 64

Run `revdep_details(, "AffiXcan")` for more info

## Newly broken

*   checking examples ... ERROR

    ...
    + tbaPaths=trainingTbaPaths, regionAssoc=regionAssoc, cov=trainingCovariates,
    + varExplained=80, scale=TRUE)
    
    AffiXcan: Training The Models
    	--> Performing Principal Components Analysis
    	--> Training Linear Models
    	Done
    > 
    > testingTbaPaths <- system.file("extdata","testing.tba.toydata.rds",
    + package="AffiXcan")
    > 
    > exprmatrix <- affiXcanImpute(tbaPaths=testingTbaPaths, affiXcanTraining=training,
    + scale=TRUE)
    
    AffiXcan: Imputing Genetically Regulated Expression (GReX)
    	--> Computing Principal Components
    	--> Imputing GReX values
    Error in matrix(nrow = nrow(pcs[[1]]), ncol = 0) : 
      non-numeric matrix extent
    Calls: affiXcanImpute -> affiXcanGReX -> matrix
    Execution halted


## In both

*   checking R code for possible problems ... NOTE

    affiXcanBs: no visible global function definition for ‘p.adjust’
    affiXcanPcs: no visible global function definition for ‘setNames’
    computeBs: no visible binding for global variable ‘V1’
    computeBs: no visible global function definition for ‘lm’
    computeBs: no visible global function definition for ‘anova’
    computeBs: no visible global function definition for ‘pf’
    computeCorrelation: no visible global function definition for ‘cor’
    computeCorrelation: no visible global function definition for
      ‘cor.test’
    computePca: no visible global function definition for ‘var’
    computePca: no visible global function definition for ‘prcomp’
    computeRSquared: no visible binding for global variable ‘exprMatrix’
    Undefined global functions or variables:
      V1 anova cor cor.test exprMatrix lm p.adjust pf prcomp setNames var
    Consider adding
      importFrom("stats", "anova", "cor", "cor.test", "lm", "p.adjust", "pf",
                 "prcomp", "setNames", "var")
    to your NAMESPACE file.

I plan to merge to the main branch and upload to Bioconductor quite soon. I can help you debug any issues
that you are having with this change. Apologies for the inconvenience.

Best regards,
Marcel