Experimental design trade-offs for gene regulatory network inference: an in silico study of the yeast Saccharomyces cerevisiae cell cycle

Time-series of high throughput gene sequencing data intended for gene regulatory network (GRN) inference are often short due to the high costs of sampling cell systems. Moreover, experimentalists lack a set of quantitative guidelines that prescribe the minimal number of samples required to infer a reliable GRN model. We study the temporal resolution of data vs quality of GRN inference in order to ultimately overcome this deficit. The evolution of a Markovian jump process model for the Ras/cAMP/PKA pathway of proteins and metabolites in the G1 phase of the Saccharomyces cerevisiae cell cycle is sampled at a number of different rates. For each time-series we infer a linear regression model of the GRN using the LASSO method. The inferred network topology is evaluated in terms of the area under the precision-recall curve AUPR. By plotting the AUPR against the number of samples, we show that the trade-off has a, roughly speaking, sigmoid shape. An optimal number of samples corresponds to values on the ridge of the sigmoid

Structural schemes of classical EXTs, LRX, and PERKs.

<p>Classical EXTs have an N-terminal signal peptide (green) followed only by EXT domain (red). LRXs have an N-terminal signal peptide (green) followed by a leucine-rich region (LRR, blue). The EXT domain (red) of LRXs is located at the C terminus. The EXT domain of PERKs is located at N terminus followed by a transmembrane domain (TMD, black) and a kinase domain (yellow).</p

Maximum Likelihood Analysis of LRXs.

<p>The evolutionary history was inferred by using the Maximum Likelihood method based on the JTT matrix-based model. The bootstrap consensus tree inferred from 1000 replicates is taken to represent the evolutionary history of the taxa analyzed. Branches corresponding to partitions reproduced in less than 50% bootstrap replicates are collapsed. The analysis involved 78 amino acid sequences. There were a total of 294 positions in the final dataset. The green-colored fan area (clades A and B) indicates LRXs from eudicot species. The yellow-colored fan area (clades C and D) indicates LRXs from monocot species. The blue-colored fan area indicates possible PEX clade. Previously reported PEXs were either marked with red “☆” or in parentheses.</p

Average number of YXY motif in classical and non-classical EXTs.

<p>The frequency was calculated as the total number of YXY repeats divided by the total number of classical and non-classical EXTs in chosen species.</p

Maximum Likelihood Analysis of PERKs.

<p>The evolutionary history was inferred by using the Maximum Likelihood method based on the JTT matrix-based model. The bootstrap consensus tree inferred from 1000 replicates is taken to represent the evolutionary history of the taxa analyzed. Branches corresponding to partitions reproduced in less than 50% bootstrap replicates are collapsed. The analysis involved 93 amino acid sequences. There were a total of 283 positions in the final dataset. A and B represent two major clades.</p

Protein sequences encoded by representative EXT gene classes in <i>Brassica rapa</i> and <i>Chlamydomonas reinhardtii</i>.

<p>Green colored sequences at the N terminus indicate predicted signal peptides. SP₃ (blue), SP₄ (red), SP₅ (purple), and YXY (dark red) repeats are also indicated. Sequences typical of AGPs, AP, PA, SP, TP, VP, and GP repeats, are also indicated (yellow).</p

The frequency of SP₃, SP₄, and SP₅ repeats in classical EXTs of selected genomes.

<p>The frequency was calculated by the total number of each type of repeat divided by the total number of SP₃, SP₄, and SP₅ adding together in each species.</p

Maximum Likelihood Analysis of FHs.

<p>The evolutionary history was inferred by using the Maximum Likelihood method based on the JTT matrix-based model. The bootstrap consensus tree inferred from 1000 replicates is taken to represent the evolutionary history of the taxa analyzed. Branches corresponding to partitions reproduced in less than 50% bootstrap replicates are collapsed. The analysis involved 73 amino acid sequences. There were a total of 377 positions in the final dataset.</p

Phylogenetic distribution of EXTs in selected plant genomes.

<p>(A) Dendrogram showing the evolutionary relationships of species selected representing major plant divisions. (B) The distribution of EXTs identified in this study and in the previous literature (Showalter et al. 2010, and unpublished data). EXTs are divided into seven subclasses including classical EXTs, short EXTs, LRXs, PERKs, FH EXTs, chimeric EXTs, and long chimeric EXTs.</p

Additional file 1: of Viral and metabolic controls on high rates of microbial sulfur and carbon cycling in wetland ecosystems

Table S1. Summary of samples. Sample names in this study are corresponded to samples names in our previous 16S rRNA gene study [9]. Genomic DNA (gDNA) concentrations obtained for each sample and total DNA retrieved are presented. (XLSX 10 kb