27,196 research outputs found
No wisdom in the crowd: genome annotation at the time of big data - current status and future prospects
Science and engineering rely on the accumulation
and dissemination of knowledge to make discoveries
and create new designs. Discovery-driven genome
research rests on knowledge passed on via gene
annotations. In response to the deluge of sequencing
big data, standard annotation practice employs automated
procedures that rely on majority rules. We
argue this hinders progress through the generation
and propagation of errors, leading investigators into
blind alleys. More subtly, this inductive process discourages
the discovery of novelty, which remains
essential in biological research and reflects the nature
of biology itself. Annotation systems, rather than
being repositories of facts, should be tools that support
multiple modes of inference. By combining
deduction, induction and abduction, investigators can
generate hypotheses when accurate knowledge is
extracted from model databases. A key stance is to
depart from âthe sequence tells the structure tells the
functionâ fallacy, placing function first. We illustrate
our approach with examples of critical or unexpected
pathways, using MicroScope to demonstrate how
tools can be implemented following the principles we
advocate. We end with a challenge to the reader
Towards a proteomics meta-classification
that can serve as a foundation for more refined ontologies in the field of proteomics. Standard data sources classify proteins in terms of just one or two specific aspects. Thus SCOP (Structural Classification of Proteins) is described as classifying proteins on the basis of structural features; SWISSPROT annotates proteins on the basis of their structure and of parameters like post-translational modifications. Such data sources are connected to each other by pairwise term-to-term mappings. However, there are obstacles which stand in the way of combining them together to form a robust meta-classification of the needed sort. We discuss some formal ontological principles which
should be taken into account within the existing datasources in order to make such a metaclassification possible, taking into account also the Gene Ontology (GO) and its application to the annotation of proteins
Spectral analysis of gene expression profiles using gene networks
Microarrays have become extremely useful for analysing genetic phenomena, but
establishing a relation between microarray analysis results (typically a list
of genes) and their biological significance is often difficult. Currently, the
standard approach is to map a posteriori the results onto gene networks to
elucidate the functions perturbed at the level of pathways. However,
integrating a priori knowledge of the gene networks could help in the
statistical analysis of gene expression data and in their biological
interpretation. Here we propose a method to integrate a priori the knowledge of
a gene network in the analysis of gene expression data. The approach is based
on the spectral decomposition of gene expression profiles with respect to the
eigenfunctions of the graph, resulting in an attenuation of the high-frequency
components of the expression profiles with respect to the topology of the
graph. We show how to derive unsupervised and supervised classification
algorithms of expression profiles, resulting in classifiers with biological
relevance. We applied the method to the analysis of a set of expression
profiles from irradiated and non-irradiated yeast strains. It performed at
least as well as the usual classification but provides much more biologically
relevant results and allows a direct biological interpretation
The astacin metalloprotease moulting enzyme NAS-36 is required for normal cuticle ecdysis in free-living and parasitic nematodes
Nematodes represent one of the most abundant and species-rich groups of animals on the planet, with parasitic species causing chronic, debilitating infections in both livestock and humans worldwide. The prevalence and success of the nematodes is a direct consequence of the exceptionally protective properties of their cuticle. The synthesis of this cuticle is a complex multi-step process, which is repeated 4 times from hatchling to adult and has been investigated in detail in the free-living nematode, Caenorhabditis elegans. This process is known as moulting and involves numerous enzymes in the synthesis and degradation of the collagenous matrix. The nas-36 and nas-37 genes in C. elegans encode functionally conserved enzymes of the astacin metalloprotease family which, when mutated, result in a phenotype associated with the late-stage moulting defects, namely the inability to remove the preceding cuticle. Extensive genome searches in the gastrointestinal nematode of sheep, Haemonchus contortus, and in the filarial nematode of humans, Brugia malayi, identified NAS-36 but not NAS-37 homologues. Significantly, the nas-36 gene from B. malayi could successfully complement the moult defects associated with C. elegans nas-36, nas-37 and nas-36/nas-37 double mutants, suggesting a conserved function for NAS-36 between these diverse nematode species. This conservation between species was further indicated when the recombinant enzymes demonstrated a similar range of inhibitable metalloprotease activities
The Ah receptor: adaptive metabolism, ligand diversity, and the xenokine model
Author Posting. © American Chemical Society, 2020. This is an open access article published under an ACS AuthorChoice License. The definitive version was published in Chemical Research in Toxicology, 33(4), (2020): 860-879, doi:10.1021/acs.chemrestox.9b00476.The Ah receptor (AHR) has been studied for almost five decades. Yet, we still have many important questions about its role in normal physiology and development. Moreover, we still do not fully understand how this protein mediates the adverse effects of a variety of environmental pollutants, such as the polycyclic aromatic hydrocarbons (PAHs), the chlorinated dibenzo-p-dioxins (âdioxinsâ), and many polyhalogenated biphenyls. To provide a platform for future research, we provide the historical underpinnings of our current state of knowledge about AHR signal transduction, identify a few areas of needed research, and then develop concepts such as adaptive metabolism, ligand structural diversity, and the importance of proligands in receptor activation. We finish with a discussion of the cognate physiological role of the AHR, our perspective on why this receptor is so highly conserved, and how we might think about its cognate ligands in the future.This review is dedicated in memory of the career of Alan Poland, one of the truly great minds in pharmacology and toxicology. This work was supported by the National Institutes of Health Grants R35-ES028377, T32-ES007015, P30-CA014520, P42-ES007381, and U01-ES1026127, The UW SciMed GRS Program, and The Morgridge Foundation. The authors would like to thank Catherine Stanley of UW Media Solutions for her artwork
Functional foods : a conceptual model for assessing their safety and effectiveness
This report shows that the product-diet dilemma can be solved by developing a predictive model. The model integrates food intake data, dynamic consumption patterns and the production chain model and combines them with a risk-benefit approach
Transcriptome assembly and profiling of Candida auris reveals novel insights into biofilm-mediated resistance
Candida auris has emerged as a significant global nosocomial pathogen. This is primarily due to its antifungal resistance profile but also its capacity to form adherent biofilm communities on a range of clinically important substrates. While we have a comprehensive understanding of how other Candida species resist and respond to antifungal challenge within the sessile phenotype, our current understanding of C. auris biofilm-mediated resistance is lacking. In this study, we are the first to perform transcriptomic analysis of temporally developing C. auris biofilms, which were shown to exhibit phase- and antifungal class-dependent resistance profiles. A de novo transcriptome assembly was performed, where sequenced sample reads were assembled into an ~11.5-Mb transcriptome consisting of 5,848 genes. Differential expression (DE) analysis demonstrated that 791 and 464 genes were upregulated in biofilm formation and planktonic cells, respectively, with a minimum 2-fold change. Adhesin-related glycosylphosphatidylinositol (GPI)-anchored cell wall genes were upregulated at all time points of biofilm formation. As the biofilm developed into intermediate and mature stages, a number of genes encoding efflux pumps were upregulated, including ATP-binding cassette (ABC) and major facilitator superfamily (MFS) transporters. When we assessed efflux pump activity biochemically, biofilm efflux was greater than that of planktonic cells at 12 and 24 h. When these were inhibited, fluconazole sensitivity was enhanced 4- to 16-fold. This study demonstrates the importance of efflux-mediated resistance within complex C. auris communities and may explain the resistance of C. auris to a range of antimicrobial agents within the hospital environment
- âŠ