Main publication:

MIIC online: a web server to reconstruct causal or non-causal networks from non-perturbative data

  • Sella N, Verny L, Uguzzoni G, Affeldt S, Isambert H
Bioinformatics 34(13):2311-2313 (2018).

Abstract

We present a web server running the MIIC algorithm, a network learning method combining constraint-based and information-theoretic frameworks to reconstruct causal, non-causal or mixed networks from non-perturbative data, without the need for an a priori choice on the class of reconstructed network. Starting from a fully connected network, the algorithm first removes dispensable edges by iteratively subtracting the most significant information contributions from indirect paths between each pair of variables. The remaining edges are then filtered based on their confidence assessment or oriented based on the signature of causality in observational data. MIIC online server can be used for a broad range of biological data, including possible unobserved (latent) variables, from single cell gene expression data to protein sequence evolution, and outperforms or matches state-of-the-art methods for either causal or non-causal network reconstruction.

Further methodological details can be found in:

Learning causal networks with latent variables from multivariate information in genomic data

  • Verny L, Sella N, Affeldt S, Singh PP, Isambert H
PLoS Comput Biol 13(10):e1005662 (2017).

Abstract

Learning causal networks from large-scale genomic data remains challenging in absence of time series or controlled perturbation experiments. We report an information-theoretic method which learns a large class of causal or non-causal graphical models from purely observational data, while including the effects of unobserved latent variables, commonly found in many genomic datasets. Starting from a complete graph, the method iteratively removes dispensable edges, by uncovering significant information contributions from indirect paths, and assesses edge-specific confidences from randomization of available data. The remaining edges are then oriented based on the signature of causality in observational data. The approach and associated algorithm, miic, outperform earlier methods on a broad range of benchmark networks. Causal network reconstructions are presented at different biological size and time scales, from gene regulation in single cells to whole genome duplication in tumor development as well as long term evolution of vertebrates.