Dataset Information

Inferring gene regulatory networks by singular value decomposition and gravitation field algorithm.

ABSTRACT: Reconstruction of gene regulatory networks (GRNs) is of utmost interest and has become a challenge computational problem in system biology. However, every existing inference algorithm from gene expression profiles has its own advantages and disadvantages. In particular, the effectiveness and efficiency of every previous algorithm is not high enough. In this work, we proposed a novel inference algorithm from gene expression data based on differential equation model. In this algorithm, two methods were included for inferring GRNs. Before reconstructing GRNs, singular value decomposition method was used to decompose gene expression data, determine the algorithm solution space, and get all candidate solutions of GRNs. In these generated family of candidate solutions, gravitation field algorithm was modified to infer GRNs, used to optimize the criteria of differential equation model, and search the best network structure result. The proposed algorithm is validated on both the simulated scale-free network and real benchmark gene regulatory network in networks database. Both the Bayesian method and the traditional differential equation model were also used to infer GRNs, and the results were used to compare with the proposed algorithm in our work. And genetic algorithm and simulated annealing were also used to evaluate gravitation field algorithm. The cross-validation results confirmed the effectiveness of our algorithm, which outperforms significantly other previous algorithms.

SUBMITTER: Zheng M

PROVIDER: S-EPMC3514269 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Inferring gene regulatory networks by singular value decomposition and gravitation field algorithm.

Zheng Ming M Wu Jia-nan JN Huang Yan-xin YX Liu Gui-xia GX Zhou You Y Zhou Chun-guang CG

PloS one 20121204 12

Reconstruction of gene regulatory networks (GRNs) is of utmost interest and has become a challenge computational problem in system biology. However, every existing inference algorithm from gene expression profiles has its own advantages and disadvantages. In particular, the effectiveness and efficiency of every previous algorithm is not high enough. In this work, we proposed a novel inference algorithm from gene expression data based on differential equation model. In this algorithm, two methods ...[more]

PMID: 23226565

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Project description:In recent years, due to the difficulty and inefficiency of experimental methods, numerous computational methods have been introduced for inferring the structure of Gene Regulatory Networks (GRNs). The Path Consistency (PC) algorithm is one of the popular methods to infer the structure of GRNs. However, this group of methods still has limitations and there is a potential for improvements in this field. For example, the PC-based algorithms are still sensitive to the ordering of nodes i.e. different node orders results in different network structures. The second is that the networks inferred by these methods are highly dependent on the threshold used for independence testing. Also, it is still a challenge to select the set of conditional genes in an optimal way, which affects the performance and computation complexity of the PC-based algorithm. We introduce a novel algorithm, namely Order Independent PC-based algorithm using Quantile value (OIPCQ), which improves the accuracy of the learning process of GRNs and solves the order dependency issue. The quantile-based thresholds are considered for different orders of CMI tests. For conditional gene selection, we consider the paths between genes with length equal or greater than 2 while other well-known PC-based methods only consider the paths of length 2. We applied OIPCQ on the various networks of the DREAM3 and DREAM4 in silico challenges. As a real-world case study, we used OIPCQ to reconstruct SOS DNA network obtained from Escherichia coli and GRN for acute myeloid leukemia based on the RNA sequencing data from The Cancer Genome Atlas. The results show that OIPCQ produces the same network structure for all the permutations of the genes and improves the resulted GRN through accurately quantifying the causal regulation strength in comparison with other well-known PC-based methods. According to the GRN constructed by OIPCQ, for acute myeloid leukemia, two regulators BCLAF1 and NRSF reported previously are significantly important. However, the highest degree nodes in this GRN are ZBTB7A and PU1 which play a significant role in cancer, especially in leukemia. OIPCQ is freely accessible at https://github.com/haammim/OIPCQ-and-OIPCQ2 .

Project description:BackgroundBoth microarrays and quantitative real-time PCR are convenient tools for studying the transcriptional levels of genes. The former is preferable for large scale studies while the latter is a more targeted technique. Because of platform-dependent systematic effects, simple comparisons or merging of datasets obtained by these technologies are difficult, even though they may often be desirable. These difficulties are exacerbated if there is only partial overlap between the experimental conditions and genes probed in the two datasets.ResultsWe show here that the generalized singular value decomposition provides a practical tool for merging a small, targeted dataset obtained by quantitative real-time PCR of specific genes with a much larger microarray dataset. The technique permits, for the first time, the identification of genes present in only one dataset co-expressed with a target gene present exclusively in the other dataset, even when experimental conditions for the two datasets are not identical. With the rapidly increasing number of publically available large scale microarray datasets the latter is frequently the case. The method enables us to discover putative candidate genes involved in the biosynthesis of the (1,3;1,4)-beta-D-glucan polysaccharide found in plant cell walls.ConclusionWe show that the generalized singular value decomposition provides a viable tool for a combined analysis of two gene expression datasets with only partial overlap of both gene sets and experimental conditions. We illustrate how the decomposition can be optimized self-consistently by using a judicious choice of genes to define it. The ability of the technique to seamlessly define a concept of "co-expression" across both datasets provides an avenue for meaningful data integration. We believe that it will prove to be particularly useful for exploiting large, publicly available, microarray datasets for species with unsequenced genomes by complementing them with more limited in-house expression measurements.

Dataset Information

Inferring gene regulatory networks by singular value decomposition and gravitation field algorithm.

Publications

Inferring gene regulatory networks by singular value decomposition and gravitation field algorithm.

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