Annotations that describe the function of sequences are enormously important to researchers during laboratory investigations and when making computational inferences. However, there has been little investigation into the data quality of sequence function annotations. Here we have developed a new method of estimating the error rate of curated sequence annotations, and applied this to the Gene Ontology (GO) sequence database (GOSeqLite). This method involved artificially adding errors to sequence annotations at known rates, and used regression to model the impact on the precision of annotations based on BLAST matched sequences.
Results
We estimated the error rate of curated GO sequence annotations in the GOSeqLite database (March 2006) at between 28% and 30%. Annotations made without use of sequence similarity based methods (non-ISS) had an estimated error rate of between 13% and 18%. Annotations made with the use of sequence similarity methodology (ISS) had an estimated error rate of 49%.
Conclusion
While the overall error rate is reasonably low, it would be prudent to treat all ISS annotations with caution. Electronic annotators that use ISS annotations as the basis of predictions are likely to have higher false prediction rates, and for this reason designers of these systems should consider avoiding ISS annotations where possible. Electronic annotators that use ISS annotations to make predictions should be viewed sceptically. We recommend that curators thoroughly review ISS annotations before accepting them as valid. Overall, users of curated sequence annotations from the GO database should feel assured that they are using a comparatively high quality source of information. 相似文献
Species from the Paracoccidioides complex are thermally dimorphic fungi and the causative agents of paracoccidioidomycosis, a deep fungal infection that is the most prevalent systemic mycosis in Latin America and represents the most important cause of death in immunocompetent individuals with systemic mycosis in Brazil. We previously described the identification of eight new families of DNA transposons in Paracoccidioides genomes. In this work, we aimed to identify potentially active retrotransposons in Paracoccidioides genomes.
Results
We identified five different retrotransposon families (four LTR-like and one LINE-like element) in the genomes of three Paracoccidioides isolates. Retrotransposons were present in all of the genomes analyzed. P. brasiliensis and P. lutzii species harbored the same retrotransposon lineages but differed in their copy numbers. In the Pb01, Pb03 and Pb18 genomes, the number of LTR retrotransposons was higher than the number of LINE-like elements, and the LINE-like element RtPc5 was transcribed in Paracoccidioides lutzii (Pb01) but could not be detected in P. brasiliensis (Pb03 and Pb18) by semi-quantitative RT-PCR.
Conclusion
Five new potentially active retrotransposons have been identified in the genomic assemblies of the Paracoccidioides species complex using a combined computational and experimental approach. The distribution across the two known species, P. brasiliensis and P. lutzii, and phylogenetics analysis indicate that these elements could have been acquired before speciation occurred. The presence of active retrotransposons in the genome may have implications regarding the evolution and genetic diversification of the Paracoccidioides genus.
Electronic supplementary material
The online version of this article (doi:10.1186/s12864-015-1564-7) contains supplementary material, which is available to authorized users. 相似文献
A large number of papers have been published on analysis of microarray data with particular emphasis on normalization of data,
detection of differentially expressed genes, clustering of genes and regulatory network. On other hand there are only few
studies on relation between expression level and composition of nucleotide/protein sequence, using expression data. There
is a need to understand why particular genes/proteins express more in particular conditions. In this study, we analyze 3468
genes of Saccharomyces cerevisiae obtained from Holstege et al., (1998) to understand the relationship between expression level and amino acid composition. 相似文献
There are few animal models of dengue infection, especially in immunocompetent mice. Here, we describe alterations found in adult immunocompetent mice inoculated with an adapted Dengue virus (DENV-3) strain. Infection of mice with the adapted DENV-3 caused inoculum-dependent lethality that was preceded by several hematological and biochemical changes and increased virus dissemination, features consistent with severe disease manifestation in humans. IFN-γ expression increased after DENV-3 infection of WT mice and this was preceded by increase in expression of IL-12 and IL-18. In DENV-3-inoculated IFN-γ(-/-) mice, there was enhanced lethality, which was preceded by severe disease manifestation and virus replication. Lack of IFN-γ production was associated with diminished NO-synthase 2 (NOS2) expression and higher susceptibility of NOS2(-/-) mice to DENV-3 infection. Therefore, mechanisms of protection to DENV-3 infection rely on IFN-γ-NOS2-NO-dependent control of viral replication and of disease severity, a pathway showed to be relevant for resistance to DENV infection in other experimental and clinical settings. Thus, the model of DENV-3 infection in immunocompetent mice described here represents a significant advance in animal models of severe dengue disease and may provide an important tool to the elucidation of immunopathogenesis of disease and of protective mechanisms associated with infection. 相似文献
Paracoccidioides brasiliensis is a temperature-dependent dimorphic fungus and the agent of paracoccidioidomycosis (PCM), which is prevalent in rural workers
of Latin American countries. Until a decade ago, most of the studies involving P. brasiliensis used clinical isolates, since environmental samples from soil are difficult to obtain. More recently, P. brasiliensis has been isolated from infected wild and domestic animals, especially from the nine-banded armadillo Dasypus novemcinctus in Brazil. Over the years, diversity within the species has been observed at several phenotypic levels. The present review
will discuss the reports focusing on genetic polymorphism, which culminated with the detection of P. brasiliensis phylogenetic species as a result of a multilocus study. Polymorphism in the PbGP43 gene is detailed. This gene encodes fungal glycoprotein gp43, a dominant P. brasiliensis antigen largely studied in the last two decades for its importance in diagnosis, immune protection, and adhesive properties
to extracellular matrix-associated proteins. Fungal traits associated with genetic groups are discussed. 相似文献
Low-lying coral reef islands are considered highly vulnerable to climate change, necessitating an improved understanding of when and why they form, and how the timing of formation varies within and among regions. Several testable models have been proposed that explain inter-regional variability as a function of sea-level history and, more recently, a reef platform size model has been proposed from the Maldives (central Indian Ocean) to explain intra-regional (intra-atoll) variability. Here we present chronostratigraphic data from Pipon Island, northern Great Barrier Reef (GBR), enabling us to test the applicability of existing regional island evolution models, and the platform size control hypothesis in a Pacific context. We show that reef platform infilling occurred rapidly (~4–5 mm yr−1) under a “bucket-fill” type scenario. Unusually, this infilling was dominated by terrigenous sedimentation, with platform filling and subsequent reef flat formation complete by ~5000 calibrated years BP (cal BP). Reef flat exposure as sea levels slowly fell post highstand facilitated a shift towards intertidal and subaerial-dominated sedimentation. Our data suggest, however, a lag of ~1500 yr before island initiation (at ~3200 cal BP), i.e. later than that reported from smaller and more evolutionarily mature reef platforms in the region. Our data thus support: (1) the hypothesis that platform size acts to influence the timing of platform filling and subsequent island development at intra-regional scales; and (2) the hypothesis that the low wooded islands of the northern GBR conform to a model of island formation above an elevated reef flat under falling sea levels.
Wnt/β-catenin signaling has come to the forefront of liver biology in recent years. This pathway regulates key pathophysiological events inherent to the liver including development, regeneration and cancer, by dictating several biological processes such as proliferation, apoptosis, differentiation, adhesion, zonation and metabolism in various cells of the liver. This review will examine the studies that have uncovered the relevant roles of Wnt/β-catenin signaling during the process of liver development. We will discuss the potential roles of Wnt/β-catenin signaling during the phases of development, including competence, hepatic induction, expansion and morphogenesis. In addition, we will discuss the role of negative and positive regulation of this pathway and how the temporal expression of Wnt/β-catenin can direct key processes during hepatic development. We will also identify some of the major deficits in the current understanding of the role of Wnt/β-catenin signaling in liver development in order to provide a perspective for future studies. Thus, this review will provide a contextual overview of the role of Wnt/β-catenin signaling during hepatic organogenesis.Key words: liver development, liver cancer, liver regeneration, Wnt signaling, proliferation, differentiationThe Wnt/β-catenin pathway is an evolutionarily well-conserved pathway that has proven to be essential to normal cellular processes such as development, growth, survival, regeneration and self-renewal.1–5 Its diverse functions also include the initiation and progression of cancer.6 In fact, one area in which this pathway has been extensively studied is in liver cancer.Mutations of Wnt/β-catenin pathway members in hepatocarcinogenesis are common. For example, 90–100% of hepatoblastomas contain mutations in adenomatous polyposis coli (APC), CTNNB1 and/or Axin1/2, which causes cytoplasmic and nuclear localization of β-catenin.7–9 Axin1 and β-catenin mutations have also been identified in approximately 25% of hepatocellular carcinomas,10–12 while overexpression of the frizzled-7 receptor13 and glycogen synthase kinase-3 (GSK-3) inactivation14 can also lead to aberrant β-catenin pathway activation. The dysregulation of this pathway in hepatic cancers makes it an attractive target for potential therapies, and experimental treatment in vivo has shown promising results. For example, inhibiting β-catenin expression by siRNA or R-Etodolac decreases proliferation and survival of human hepatoma cell lines.15,16 Since cancer recapitulates development, determining the timing of β-catenin activation during hepatogenesis will help us to better understand the inappropriate activation of this pathway in hepatocarcinogenesis.Recent work has elucidated the role of β-catenin signaling in the liver, and has highlighted its essential role in liver health and disease.17 In addition, emerging evidence suggests that this pathway plays a key role in liver organogenesis. 相似文献
One of the major challenges in post-genomic era is to provide functional annotations for large number of proteins arising
from genome sequencing projects. The function of many proteins depends on their interaction with small molecules or ligands.
ATP is one such important ligand that plays critical role as a coenzyme in the functionality of many proteins. There is a
need to develop method for identifying ATP interacting residues in a ATP binding proteins (ABPs), in order to understand mechanism
of protein-ligands interaction. 相似文献