MiCoViTo: a tool for gene-centric comparison and visualization of yeast transcriptome states

Abstract

Background: Information obtained by DNA microarray technology gives a rough snapshot of the transcriptome state, i.e., the expression level of all the genes expressed in a cell population at any given time. One of the challenging questions raised by the tremendous amount of microarray data is to identify groups of co-regulated genes and to understand their role in cell functions.

Results: MiCoViTo (Microarray Comparison Visualization Tool) is a set of biologists' tools for exploring, comparing and visualizing changes in the yeast transcriptome by a gene-centric approach. A relational database includes data linked to genome expression and graphical output makes it easy to visualize clusters of co-expressed genes in the context of available biological information. To this aim, upload of personal data is possible and microarray data from fifty publications dedicated to S. cerevisiae are provided on-line. A web interface guides the biologist during the usage of this tool and is freely accessible at http://www.transcriptome.ens.fr/micovito/.

Conclusions: MiCoViTo offers an easy-to-read picture of local transcriptional changes connected to current biological knowledge. This should help biologists to mine yeast microarray data and better understand the underlying biology. We plan to add functional annotations from other organisms. That would allow inter-species comparison of transcriptomes via orthology tables.

Figure 1

MiCoViTo principle A) Neighbourhood comparison around a seed in two transcriptome states. The location of genes gives an idea of their expression compared to the seed gene. The X axis represents the neighbourhood levels computed in the first transcriptome state, the Y axis represents the neighbourhood levels computed in the second transcriptome state. Regions that are closer to the origin reflect more closely co-expressed genes (delimited by red dash lines). The white region is the area containing genes correlated in both microarray datasets while the blue area contains genes that are co-expressed only in one of the conditions. As we do not want to consider genes that are far away from the seed gene in both transcriptome states, the lower right part of the table is not analysed (grey region). B) Result of the comparison of S. cerevisiae transcriptome state time courses during a 30°C to 37°C temperature shift and during exposure to the reducing agent dithiotreitol (DTT) [29] available in the online tutorial. The comparison was performed using a structural constituent of a ribosome subunit (RPS8B/YER102W gene) as seed and Pearson distance as the distance metric. The step value used to define neigbourhood levels is 0.2 (see intervals 0–0.2, 0.2–0.4, ..., 1.2–1.4). Each group of genes located in a neighbourhood intersection is given in the form of a clickable pie chart constructed according to the MIPS functional classification catalogue [15].

Figure 2

Example of study A) Neighbourhood comparison using two distinct seeds and a single transcriptome state. The results depend on the relative position of the seed genes in the overall transcriptome. This example shows the best-case scenario: two genes close to each other, with a circular gradient of expression coherence. This leads to the definition of zone of interest, represented here in red, which contains genes that are close to both seed genes. These genes are the other partners of the cluster defined by seeds 1 and 2. B) Results of the neighbourhood comparison of the two distincts seeds CLN1/CLN2 (B2) and CLN1/CLB2 (B3) in the Cho et al. yeast cell cycle datasets [23]. CLN1 and CLN2 are both involved in the G1 phase whereas CLB2 is involved in the G2/M transition (B1). Each induced group of genes is represented in the form of a pie chart showing gene distribution in each cell cycle phase (color code is provided in B1 diagram, red: G1; dark green: S; orange: S/G2; blue: G2/M; light green: M/G1).