Adriaan’s paper “Comparison between instrumental variable and mediation-based methods for reconstructing causal gene networks in yeast” has been posted on biorXiv. In this paper we used Findr to compare several methods for causal inference from genomics and transcriptomics data, using a recently published dataset of 1,012 segregants from a cross between two budding yeast strains.
Lingfei’s paper, “High-dimensional Bayesian network inference from systems genetics data using genetic node ordering” has been published in Frontiers in Genetics, in a Special Topic on Machine Learning and Network-Driven Integrative Genomics.
In this paper, we present a highly efficient approach for reconstructing Bayesian gene regulatory networks when prior information for the inclusion of edges exists or can be inferred from the available data. The method is implemented in the Findr software.
Pau’s paper “Model-based clustering of multi-tissue gene expression data” has been published in Bioinformatics. In this paper a method, called “revamp”, is introduced to find clusters (groups of genes with shared activity patterns) in multi-tissue data, where gene expression profiles are available from multiple tissues or organs sampled from the same group of individuals. Revamp improves existing methods by its ability to incorporate prior information on physiological tissue similarity, and by identifying a set of clusters, each consisting of a core set of genes conserved across tissues as well as differential sets of genes specific to one or more subsets of tissues. Revamp is implemented in the Lemon-Tree software.
A new preprint, “High-dimensional Bayesian network inference from systems genetics data using genetic node ordering”, is available on bioRxiv. Bayesian networks are statistical models for gene regulatory networks, and their inference from large-scale omics data is a major problem in systems genetics. In this paper we present an algorithm to solve this problem that uses causal inference, topological sorting and variable selection, and that is much more efficient than traditional Markov chain Monte Carlo algorithms. The algorithm is implemented in the Findr and lassopv software packages.
We contributed two chapters to a Methods in Molecular Biology book on Gene Regulatory Networks: a chapter by Lingfei about the use of Findr for the inference of transcriptome-wide causal networks, and a chapter by Pau about the use of lemon-tree for the inference of differential module networks.
There is a lot of research showing that genetic information in combination with gene expression data can be used to predict causal interactions between genes, on the basis that genetic variation among individuals causes gene expression variation but not vice versa (this PLOS CompBio article is a contribution to the field from our group and has links to earlier work). Anagha Joshi’s group asked if this principle could be extended to other contexts, and in a joint preprint “Causal gene regulatory network inference using enhancer activity as a causal anchor” an affirmative answer is given: variation of epigenetic activity at enhancer elements across multiple cell types or experimental treatments together with gene expression data also predicts causal interactions. The accompanying statistical methods have been implemented in our Findr software.
A preprint on “Model-based clustering of multi-tissue gene expression data” is available from arXiv. In this paper we present a Bayesian model-based clustering algorithm for large-scale, multi-tissue gene expression data, where expression profiles are obtained from multiple tissues or organs sampled from dozens to hundreds of individuals. Our model can incorporate prior information on physiological tissue similarity, and results in a set of clusters, each consisting of a core set of genes conserved across tissues as well as differential sets of genes specific to one or more subsets of tissues. The algorithm has been implemented in the Lemon-Tree software as a new “task”, revamp.
We have contributed two chapters to a forthcoming book on gene regulatory network inference edited by Vân Anh Huynh-Thu and Guido Sanguinetti.
Whole-transcriptome causal network inference with genomic and transcriptomic data (on bioRxiv) describes a protocol for reconstructing causal gene networks from genome-wide genotype and gene expression data using the Findr software.
Learning differential module networks across multiple experimental conditions (on arXiv) reviews the theory of module network inference and describes how differential module networks across multiple experimental conditions can be learned using the Lemon-Tree software.
We have posted a preprint “Efficient causal inference with hidden confounders from genome-transcriptome variation data”. In this paper we introduce a new method for causal inference between gene expression traits using the DNA variations in cis-regulatory regions as causal anchors. The method has been implemented in the Findr software, and validated using the DREAM5 Systems Genetics Challenge and GEUVADIS datasets.