A very important topic in systems biology is developing statistical methods that automatically find causal relations in gene regulatory networks with no prior knowledge of causal connectivity. Many methods have been developed for time series data. However, discovery methods based on steady-state data are often necessary and preferable since obtaining time series data can be more expensive and/or infeasible for many biological systems. A conventional approach is causal Bayesian networks. However, estimation of Bayesian networks is ill-posed. In many cases it cannot uniquely identify the underlying causal network and only gives a large class of equivalent causal networks that cannot be distinguished between based on the data distribution. We propose a new discovery algorithm for uniquely identifying the underlying causal network of genes. To the best of our knowledge, the proposed method is the first algorithm for learning gene networks based on a fully identifiable causal model called LiNGAM. We here compare our algorithm with competing algorithms using artificially-generated data, although it is definitely better to test it based on real microarray gene expression data.
In recent years, several methods have been proposed for the discovery of causal structure from non-experimental data (Spirtes et al. 2000; Pearl 2000). Such methods make various assumptions on the data generating process to facilitate its identification from purely observational data. Continuing this line of research, we show how to discover the complete causal structure of continuous-valued data, under the assumptions that (a) the data generating process is linear, (b) there are no unobserved confounders, and (c) disturbance variables have non-gaussian distributions of non-zero variances. The solution relies on the use of the statistical method known as independent component analysis (ICA), and does not require any pre-specified time-ordering of the variables. We provide a complete Matlab package for performing this LiNGAM analysis (short for Linear Non-Gaussian Acyclic Model), and demonstrate the effectiveness of the method using artificially generated data.
An important task in data analysis is the discovery of causal relationships between observed variables. For continuous-valued data, linear acyclic causal models are commonly used to model the data-generating process, and the inference of such models is a well-studied problem. However, existing methods have significant limitations. Methods based on conditional independencies (Spirtes et al. 1993; Pearl 2000) cannot distinguish between independence-equivalent models, whereas approaches purely based on Independent Component Analysis (Shimizu et al. 2006) are inapplicable to data which is partially Gaussian. In this paper, we generalize and combine the two approaches, to yield a method able to learn the model structure in many cases for which the previous methods provide answers that are either incorrect or are not as informative as possible. We give exact graphical conditions for when two distinct models represent the same family of distributions, and empirically demonstrate the power of our method through thorough simulations.
We consider to learn a causal ordering of variables in a linear non-Gaussian acyclic model called LiNGAM. Several existing methods have been shown to consistently estimate a causal ordering assuming that all the model assumptions are correct. But, the estimation results could be distorted if some assumptions actually are violated. In this paper, we propose a new algorithm for learning causal orders that is robust against one typical violation of the model assumptions: latent confounders. We demonstrate the effectiveness of our method using artificial data.
Discovering causal relations among observed variables in a given data set is a main topic in studies of statistics and artificial intelligence. Recently, some techniques to discover an identifiable causal structure have been explored based on non-Gaussianity of the observed data distribution. However, most of these are limited to continuous data. In this paper, we present a novel causal model for binary data and propose a new approach to derive an identifiable causal structure governing the data based on skew Bernoulli distributions of external noise. Experimental evaluation shows excellent performance for both artificial and real world data sets.
A linear non-Gaussian structural equation model called LiNGAM is an identifiable model for exploratory causal analysis. Previous methods estimate a causal ordering of variables and their connection strengths based on a single dataset. However, in many application domains, data are obtained under different conditions, that is, multiple datasets are obtained rather than a single dataset. In this paper, we present a new method to jointly estimate multiple LiNGAMs under the assumption that the models share a causal ordering but may have different connection strengths and differently distributed variables. In simulations, the new method estimates the models more accurately than estimating them separately.
Structural equation models and Bayesian networks have been widely used to analyze causal relations between continuous variables. In such frameworks, linear acyclic models are typically used to model the data-generating process of variables. Recently, it was shown that use of non-Gaussianity identifies the full structure of a linear acyclic model, i.e., a causal ordering of variables and their connection strengths, without using any prior knowledge on the network structure, which is not the case with conventional methods. However, existing estimation methods are based on iterative search algorithms and may not converge to a correct solution in a finite number of steps. In this paper, we propose a new direct method to estimate a causal ordering and connection strengths based on non-Gaussianity. In contrast to the previous methods, our algorithm requires no algorithmic parameters and is guaranteed to converge to the right solution within a small fixed number of steps if the data strictly follows the model.
Many statistical methods have been proposed to estimate causal models in classical situations with fewer variables than observations (p<n, p: the number of variables and n: the number of observations). However, modern datasets including gene expression data need high-dimensional causal modeling in challenging situations with orders of magnitude more variables than observations (p>>n). In this paper, we propose a method to find exogenous variables in a linear non-Gaussian causal model, which requires much smaller sample sizes than conventional methods and works even when p>>n. The key idea is to identify which variables are exogenous based on non-Gaussianity instead of estimating the entire structure of the model. Exogenous variables work as triggers that activate a causal chain in the model, and their identification leads to more efficient experimental designs and better understanding of the causal mechanism. We present experiments with artificial data and real-world gene expression data to evaluate the method.
Finding the structure of a graphical model has been received much attention in many fields. Recently, it is reported that the non-Gaussianity of data enables us to identify the structure of a directed acyclic graph without any prior knowledge on the structure. In this paper, we propose a novel non-Gaussianity based algorithm for more general type of models; chain graphs. The algorithm finds an ordering of the disjoint subsets of variables by iteratively evaluating the independence between the variable subset and the residuals when the remaining variables are regressed on those. However, its computational cost grows exponentially according to the number of variables. Therefore, we further discuss an efficient approximate approach for applying the algorithm to large sized graphs. We illustrate the algorithm with artificial and real-world datasets.
Structural equation models and Bayesian networks have been widely used to study causal relationships between continuous variables. Recently, a non-Gaussian method called LiNGAM was proposed to discover such causal models and has been extended in various directions. An important problem with LiNGAM is that the results are affected by the random sampling of the data as with any statistical method. Thus, some analysis of the statistical reliability or confidence level should be conducted. A common method to evaluate a confidence level is a bootstrap method. However, a confidence level computed by ordinary bootstrap method is known to be biased as a probability-value ($p$-value) of hypothesis testing. In this paper, we propose a new procedure to apply an advanced bootstrap method called multiscale bootstrap to compute confidence levels, i.e., p-values, of LiNGAM outputs. The multiscale bootstrap method gives unbiased $p$-values with asymptotic much higher accuracy. Experiments on artificial data demonstrate the utility of our approach.