InterPro in 2017-beyond protein family and domain annotations

InterPro (http://www.ebi.ac.uk/interpro/) is a freely available database used to classify protein sequences into families and to predict the presence of important domains and sites. InterProScan is the underlying software that allows both protein and nucleic acid sequences to be searched against InterPro's predictive models, which are provided by its member databases. Here, we report recent developments with InterPro and its associated software, including the addition of two new databases (SFLD and CDD), and the functionality to include residue-level annotation and prediction of intrinsic disorder. These developments enrich the annotations provided by InterPro, increase the overall number of residues annotated and allow more specific functional inferences

Circadian clock mechanism driving mammalian photoperiodism.

The annual photoperiod cycle provides the critical environmental cue synchronizing rhythms of life in seasonal habitats. In 1936, Bünning proposed a circadian-basis for photoperiodic synchronization. Here, light-dark cycles entrain a circadian rhythm of photosensitivity, and the expression of summer or winter biology depends on whether light coincides with the phase of high photosensitivity. Formal studies support the universality of this so-called coincidence timer, but we lack understanding of the mechanisms involved. Here we show in mammals that coincidence timing takes place in the pars tuberalis of the pituitary, through a melatonin-dependent flip-flop switch between circadian transcriptional activation and repression. Long photoperiods produce short night-time melatonin signals, leading to induction of the circadian transcription factor BMAL2, in turn triggering summer biology through the eyes absent / thyrotrophin (EYA3 / TSH) pathway. Conversely, short photoperiods produce long melatonin signals, inducing circadian repressors including DEC1, in turn suppressing BMAL2 and the EYA3/TSH pathway, triggering winter biology. These actions are associated with progressive genome-wide changes in chromatin state, elaborating the effect of the circadian coincidence timer. Hence, circadian clock interactions with pituitary epigenetic pathways form the basis of the mammalian coincidence timer mechanism. Our results constitute a blueprint for circadian-based seasonal timekeeping in vertebrates

Spt6 is a maintenance factor for centromeric CENP-A

Replication and transcription of genomic DNA requires partial disassembly of nucleosomes to allow progression of polymerases. This presents both an opportunity to remodel the underlying chromatin and a danger of losing epigenetic information. Centromeric transcription is required for stable incorporation of the centromere-specific histone dCENP-A in M/G1 phase, which depends on the eviction of previously deposited H3/H3.3-placeholder nucleosomes. Here we demonstrate that the histone chaperone and transcription elongation factor Spt6 spatially and temporarily coincides with centromeric transcription and prevents the loss of old CENP-A nucleosomes in both Drosophila and human cells. Spt6 binds directly to dCENP-A and dCENP-A mutants carrying phosphomimetic residues alleviate this association. Retention of phosphomimetic dCENP-A mutants is reduced relative to wildtype, while non-phosphorylatable dCENP-A retention is increased and accumulates at the centromere. We conclude that Spt6 acts as a conserved CENP-A maintenance factor that ensures long-term stability of epigenetic centromere identity during transcription-mediated chromatin remodeling

The anti-bacterial iron-restriction defence mechanisms of egg white; the potential role of three lipocalin-like proteins in resistance against Salmonella

Salmonella enterica serovar Enteritidis (SE) is the most frequently-detected Salmonella in foodborne outbreaks in the European Union. Among such outbreaks, egg and egg products were identified as the most common vehicles of infection. Possibly, the major antibacterial property of egg white is iron restriction, which results from the presence of the iron-binding protein, ovotransferrin. To circumvent iron restriction, SE synthesise catecholate siderophores (i.e. enterobactin and salmochelin) that can chelate iron from host iron-binding proteins. Here, we highlight the role of lipocalin-like proteins found in egg white that could enhance egg-white iron restriction through sequestration of certain siderophores, including enterobactin. Indeed, it is now apparent that the egg-white lipocalin, Ex-FABP, can inhibit bacterial growth via its siderophore-binding capacity in vitro. However, it remains unclear whether ex-FABP performs such a function in egg white or during bird infection. Regarding the two other lipocalins of egg white (Cal-γ and α-1-glycoprotein), there is currently no evidence to indicate that they sequester siderophores

InterPro in 2019: improving coverage, classification and access to protein sequence annotations

The InterPro database (http://www.ebi.ac.uk/interpro/) classifies protein sequences into families and predicts the presence of functionally important domains and sites. Here, we report recent developments with InterPro (version 70.0) and its associated software, including an 18% growth in the size of the database in terms on new InterPro entries, updates to content, the inclusion of an additional entry type, refined modelling of discontinuous domains, and the development of a new programmatic interface and website. These developments extend and enrich the information provided by InterPro, and provide greater flexibility in terms of data access. We also show that InterPro's sequence coverage has kept pace with the growth of UniProtKB, and discuss how our evaluation of residue coverage may help guide future curation activities

Progress and Research Needs of Plant Biomass Degradation by Basidiomycete Fungi

Peer reviewe

Molecular signatures of the rediae, cercariae and adult stages in the complex life cycles of parasitic flatworms (Digenea: Psilostomatidae)

BACKGROUND: Parasitic flatworms (Trematoda: Digenea) represent one of the most remarkable examples of drastic morphological diversity among the stages within a life cycle. Which genes are responsible for extreme differences in anatomy, physiology, behavior, and ecology among the stages? Here we report a comparative transcriptomic analysis of parthenogenetic and amphimictic generations in two evolutionary informative species of Digenea belonging to the family Psilostomatidae. METHODS: In this study the transcriptomes of rediae, cercariae and adult worm stages of Psilotrema simillimum and Sphaeridiotrema pseudoglobulus, were sequenced and analyzed. High-quality transcriptomes were generated, and the reference sets of protein-coding genes were used for differential expression analysis in order to identify stage-specific genes. Comparative analysis of gene sets, their expression dynamics and Gene Ontology enrichment analysis were performed for three life stages within each species and between the two species.RESULTS: Reference transcriptomes for P. simillimum and S. pseudoglobulus include 21,433 and 46,424 sequences, respectively. Among 14,051 orthologous groups (OGs), 1354 are common and specific for two analyzed psilostomatid species, whereas 13 and 43 OGs were unique for P. simillimum and S. pseudoglobulus, respectively. In contrast to P. simillimum, where more than 60% of analyzed genes were active in the redia, cercaria and adult worm stages, in S. pseudoglobulus less than 40% of genes had such a ubiquitous expression pattern. In general, 7805 (36.41%) and 30,622 (65.96%) of genes were preferentially expressed in one of the analyzed stages of P. simillimum and S. pseudoglobulus, respectively. In both species 12 clusters of co-expressed genes were identified, and more than a half of the genes belonging to the reference sets were included into these clusters. Functional specialization of the life cycle stages was clearly supported by Gene Ontology enrichment analysis.CONCLUSIONS: During the life cycles of the two species studied, most of the genes change their expression levels considerably, consequently the molecular signature of a stage is not only a unique set of expressed genes, but also the specific levels of their expression. Our results indicate unexpectedly high level of plasticity in gene regulation between closely related species. Transcriptomes of P. simillimum and S. pseudoglobulus provide high quality reference resource for future evolutionary studies and comparative analyses

Defining new criteria for selection of cell-based intestinal models using publicly available databases.

BACKGROUND: The criteria for choosing relevant cell lines among a vast panel of available intestinal-derived lines exhibiting a wide range of functional properties are still ill-defined. The objective of this study was, therefore, to establish objective criteria for choosing relevant cell lines to assess their appropriateness as tumor models as well as for drug absorption studies. RESULTS: We made use of publicly available expression signatures and cell based functional assays to delineate differences between various intestinal colon carcinoma cell lines and normal intestinal epithelium. We have compared a panel of intestinal cell lines with patient-derived normal and tumor epithelium and classified them according to traits relating to oncogenic pathway activity, epithelial-mesenchymal transition (EMT) and stemness, migratory properties, proliferative activity, transporter expression profiles and chemosensitivity. For example, SW480 represent an EMT-high, migratory phenotype and scored highest in terms of signatures associated to worse overall survival and higher risk of recurrence based on patient derived databases. On the other hand, differentiated HT29 and T84 cells showed gene expression patterns closest to tumor bulk derived cells. Regarding drug absorption, we confirmed that differentiated Caco-2 cells are the model of choice for active uptake studies in the small intestine. Regarding chemosensitivity we were unable to confirm a recently proposed association of chemo-resistance with EMT traits. However, a novel signature was identified through mining of NCI60 GI50 values that allowed to rank the panel of intestinal cell lines according to their drug responsiveness to commonly used chemotherapeutics. CONCLUSIONS: This study presents a straightforward strategy to exploit publicly available gene expression data to guide the choice of cell-based models. While this approach does not overcome the major limitations of such models, introducing a rank order of selected features may allow selecting model cell lines that are more adapted and pertinent to the addressed biological question