YEASTRACT+: a portal for cross-species comparative genomics of transcription regulation in yeasts

Abstract

The YEASTRACT+ information system (http://YEASTRACT-PLUS.org/) is a wide-scope tool for the analysis and prediction of transcription regulatory associations at the gene and genomic levels in yeasts of biotechnological or human health relevance. YEASTRACT+ is a new portal that integrates the previously existing YEASTRACT (http://www.yeastract.com/) and PathoYeastract (http://pathoyeastract.org/) databases and introduces the NCYeastract (Non-Conventional Yeastract) database (http://ncyeastract.org/), focused on the so-called non-conventional yeasts. The information in the YEASTRACT database, focused on Saccharomyces cerevisiae, was updated. PathoYeastract was extended to include two additional pathogenic yeast species: Candida parapsilosis and Candida tropicalis. Furthermore, the NCYeastract database was created, including five biotechnologically relevant yeast species: Zygosaccharomyces baillii, Kluyveromyces lactis, Kluyveromyces marxianus, Yarrowia lipolytica and Komagataella phaffii. The YEASTRACT+ portal gathers 289 706 unique documented regulatory associations between transcription factors (TF) and target genes and 420 DNA binding sites, considering 247 TFs from 10 yeast species. YEASTRACT+ continues to make available tools for the prediction of the TFs involved in the regulation of gene/genomic expression. In this release, these tools were upgraded to enable predictions based on orthologous regulatory associations described for other yeast species, including two new tools for cross-species transcription regulation comparison, based on multi-species promoter and TF regulatory network analyses.

Gene Regulatory Networks of Penicillium echinulatum 2HH and Penicillium oxalicum 114-2 Inferred by a Computational Biology Approach

“…Regulatory interactions from A. nidulans, N. crassa (Hu et al, 2018), and S. cerevisiae available in YEASTRACT+ (Monteiro et al, 2020) were collected and organized in tab-delimited files. All interactions are available in Supplementary Table 2.…”

“…So far, in the fungi scope, S. cerevisiae S288C, N. crassa OR74A, and A. nidulans FGSC A4 have in-depth studies for GRN reconstruction (Hu et al, 2018;Jackson et al, 2020), whereas, for the genus Penicillium, no global GRNs have been described. The reconstruction of GRN in S. cerevisiae was, in particular, facilitated by the YEASTRACT+ database, which gathers interaction information for this organism, comprising 12,228 interactions (Jackson et al, 2020;Monteiro et al, 2020). In this regard, curated data of A. nidulans and N. crassa regulatory interactions may be useful as a catalog for gene regulation studies in filamentous fungi, since 33 conserved regulatory interactions, supported by classical experiments were identified in both species (Hu et al, 2018).…”

Trans-acting genetic variation affects the expression of adjacent genes

“…In S. cerevisiae , adjacent genes tend to be regulated by similar sets of transcription factors (Hershberg et al, 2005) , likely because genes with similar functions tend to be located together in the genome (see below and (Cohen et al, 2000;Eldabagh et al, 2018) ). To examine whether paired hotspot effects may result from shared regulation by transcription factors, we gathered annotated transcription factor binding sites (TFBS; (Monteiro et al, 2020) ) in the intergenic region upstream of each gene and calculated the similarity of these TFBS annotations among all gene pairs. Adjacent genes had higher similarity in their TFBS profiles than non-adjacent genes (Median 0.294 vs 0.275, Wilcoxon test p < 2.2×10 -16 ), as expected (Hershberg et al, 2005) .…”

“…We used a curated collection of transcription factors annotated to regulate each gene in the yeast genome (Monteiro et al, 2020) . These data were binary, with a value of zero indicating that a given TF is not known to regulate a given gene, and a value of one indicating that it does.…”

Assessing regulatory features of the current transcriptional network of Saccharomyces cerevisiae

“…In this paper, we recovered the full network of transcriptional regulatory associations currently known for S. cerevisiae, as gathered in the latest YEASTRACT release 15 . Annotations in YEASTRACT were used to produce subnetworks that encompass associations supported by binding and/or expression evidence.…”