Gene Network Landscape of the Ciliate Tetrahymena thermophila

Abstract

BackgroundGenome-wide expression data of gene microarrays can be used to infer gene networks. At a cellular level, a gene network provides a picture of the modules in which genes are densely connected, and of the hub genes, which are highly connected with other genes. A gene network is useful to identify the genes involved in the same pathway, in a protein complex or that are co-regulated. In this study, we used different methods to find gene networks in the ciliate Tetrahymena thermophila, and describe some important properties of this network, such as modules and hubs.Methodology/Principal FindingsUsing 67 single channel microarrays, we constructed the Tetrahymena gene network (TGN) using three methods: the Pearson correlation coefficient (PCC), the Spearman correlation coefficient (SCC) and the context likelihood of relatedness (CLR) algorithm. The accuracy and coverage of the three networks were evaluated using four conserved protein complexes in yeast. The CLR network with a Z-score threshold 3.49 was determined to be the most robust. The TGN was partitioned, and 55 modules were found. In addition, analysis of the arbitrarily determined 1200 hubs showed that these hubs could be sorted into six groups according to their expression profiles. We also investigated human disease orthologs in Tetrahymena that are missing in yeast and provide evidence indicating that some of these are involved in the same process in Tetrahymena as in human.Conclusions/SignificanceThis study constructed a Tetrahymena gene network, provided new insights to the properties of this biological network, and presents an important resource to study Tetrahymena genes at the pathway level.

Phosphoproteomic Analysis of Protein Phosphorylation Networks in Tetrahymena thermophila, a Model Single-celled Organism

“…A phosphoprotein network was built on correlations (z-score, calculated with a context likelihood of relatedness algorithm) of pairwise phosphoprotein genes extracted from the published T. thermophila gene network (26). The correlation cutoff value that was used to establish the phosphoprotein network was the same as in a previous study (26). The Cytoscape software (version 2.6) was used for network visualization (45).…”

“…These results provide the first and most extensive data on S/T/Y phosphorylation currently available on T. thermophila and novel insights into the range of functions regulated by S/T/Y phosphorylation in T. thermophila. Recently, we reported a comprehensive transcriptome analysis of T. thermophila, with the aim of refining its genome annotation (25,26). In this study, integrated analysis of the T. thermophila phosphoproteome and transcriptome revealed the potential biological functions of many previously unannotated proteins.…”

Toxicogenomic investigation of Tetrahymena thermophila exposed to dichlorodiphenyltrichloroethane (DDT), tributyltin (TBT), and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)

“…We applied the context likelihood of relatedness (CLR) algorithm [26] with a Z-score threshold of 3.49 to construct a Tetrahymena gene-interaction network using data from 67 NimbleGen single channel microarrays, including 52 microarrays from Gorovsky's lab and Miao's lab, 11 from the Pearlman's lab and four from Liu's lab [21]. Three stages of the life cycle were involved in these microarrays, growth, starvation and conjugation.…”

“…Three stages of the life cycle were involved in these microarrays, growth, starvation and conjugation. For growth, cells were harvested when grown to 1×10 for use in constructing the gene-interaction network [21]. Subsequently, genes with enriched functions in TCDD set were selected as cores and genes that might interact with them were extracted, after which the interactions among the extracted genes were identified according to the network.…”

“…Recently, differentially expressed genes in T. thermophila exposed to DDT or TBT have been detected using genome-wide screening conducted by suppression subtractive hybridization [18,19]. Moreover, completion of the macronuclear sequencing project [16] and establishment of the first genome-wide microarray platform in T. thermophila [20] with the Tetrahymena Gene Expression Database (TGED, http://tged.ihb.ac.cn) [21] offers extensive resources for further functional genomic studies, including toxigenomics. Thus, there is an opportunity to make use of this unicellular model to study the toxicological mechanism of environmental hormones at the genomic level.…”