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2015 ; 16
(ä): 395
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High-order dynamic Bayesian Network learning with hidden common causes for causal
gene regulatory network
#MMPMID26608050
Lo LY
; Wong ML
; Lee KH
; Leung KS
BMC Bioinformatics
2015[Nov]; 16
(ä): 395
PMID26608050
show ga
BACKGROUND: Inferring gene regulatory network (GRN) has been an important topic
in Bioinformatics. Many computational methods infer the GRN from high-throughput
expression data. Due to the presence of time delays in the regulatory
relationships, High-Order Dynamic Bayesian Network (HO-DBN) is a good model of
GRN. However, previous GRN inference methods assume causal sufficiency, i.e. no
unobserved common cause. This assumption is convenient but unrealistic, because
it is possible that relevant factors have not even been conceived of and
therefore un-measured. Therefore an inference method that also handles hidden
common cause(s) is highly desirable. Also, previous methods for discovering
hidden common causes either do not handle multi-step time delays or restrict that
the parents of hidden common causes are not observed genes. RESULTS: We have
developed a discrete HO-DBN learning algorithm that can infer also hidden common
cause(s) from discrete time series expression data, with some assumptions on the
conditional distribution, but is less restrictive than previous methods. We
assume that each hidden variable has only observed variables as children and
parents, with at least two children and possibly no parents. We also make the
simplifying assumption that children of hidden variable(s) are not linked to each
other. Moreover, our proposed algorithm can also utilize multiple short time
series (not necessarily of the same length), as long time series are difficult to
obtain. CONCLUSIONS: We have performed extensive experiments using synthetic data
on GRNs of size up to 100, with up to 10 hidden nodes. Experiment results show
that our proposed algorithm can recover the causal GRNs adequately given the
incomplete data. Using the limited real expression data and small subnetworks of
the YEASTRACT network, we have also demonstrated the potential of our algorithm
on real data, though more time series expression data is needed.