Is the crowd better as an assistant or a replacement in ontology engineering? An exploration through the lens of the Gene Ontology

Biomedical ontologies contain errors. Crowdsourcing, defined as taking a job traditionally performed by a designated agent and outsourcing it to an undefined large group of people, provides scalable access to humans. Therefore, the crowd has the potential overcome the limited accuracy and scalability found in current ontology quality assurance approaches. Crowd-based methods have identified errors in SNOMED CT, a large, clinical ontology, with an accuracy similar to that of experts, suggesting that crowdsourcing is indeed a feasible approach for identifying ontology errors. This work uses that same crowd-based methodology, as well as a panel of experts, to verify a subset of the Gene Ontology (200 relationships). Experts identified 16 errors, generally in relationships referencing acids and metals. The crowd performed poorly in identifying those errors, with an area under the receiver operating characteristic curve ranging from 0.44 to 0.73, depending on the methods configuration. However, when the crowd verified what experts considered to be easy relationships with useful definitions, they performed reasonably well. Notably, there are significantly fewer Google search results for Gene Ontology concepts than SNOMED CT concepts. This disparity may account for the difference in performance – fewer search results indicate a more difficult task for the worker. The number of Internet search results could serve as a method to assess which tasks are appropriate for the crowd. These results suggest that the crowd fits better as an expert assistant, helping experts with their verification by completing the easy tasks and allowing experts to focus on the difficult tasks, rather than an expert replacement

Comparative Analysis of Tandem Repeats from Hundreds of Species Reveals Unique Insights into Centromere Evolution

Centromeres are essential for chromosome segregation, yet their DNA sequences evolve rapidly. In most animals and plants that have been studied, centromeres contain megabase-scale arrays of tandem repeats. Despite their importance, very little is known about the degree to which centromere tandem repeats share common properties between different species across different phyla. We used bioinformatic methods to identify high-copy tandem repeats from 282 species using publicly available genomic sequence and our own data. The assumption that the most abundant tandem repeat is the centromere DNA was true for most species whose centromeres have been previously characterized, suggesting this is a general property of genomes. Our methods are compatible with all current sequencing technologies. Long Pacific Biosciences sequence reads allowed us to find tandem repeat monomers up to 1,419 bp. High-copy centromere tandem repeats were found in almost all animal and plant genomes, but repeat monomers were highly variable in sequence composition and in length. Furthermore, phylogenetic analysis of sequence homology showed little evidence of sequence conservation beyond ~50 million years of divergence. We find that despite an overall lack of sequence conservation, centromere tandem repeats from diverse species showed similar modes of evolution, including the appearance of higher order repeat structures in which several polymorphic monomers make up a larger repeating unit. While centromere position in most eukaryotes is epigenetically determined, our results indicate that tandem repeats are highly prevalent at centromeres of both animals and plants. This suggests a functional role for such repeats, perhaps in promoting concerted evolution of centromere DNA across chromosomes

Dietary omega-3 fatty acids aid in the modulation of inflammation and metabolic health

This article focuses on the role of omega-3 fatty acids as precursors for lipid signaling molecules known as oxylipins. Although omega-3 fatty acids are beneficial in autoimmune disorders, inflammatory diseases and heart disease, they are generally underrepresented in the American diet. A literature review confirms that the consumption of omega-3 fatty acids - whether in food sources such as walnuts, flax seeds and fatty fish (including salmon and sardines), or in supplements - is associated with decreased morbidity and mortality. This growing body of evidence, including the results of a recent study of patients with kidney disease, highlights the need to measure omega-3 fatty acids and their oxylipin products as markers of metabolic health and biomarkers of disease. In addition, there is substantial evidence of the need to increase the omega-3 fatty acid content of American diets to optimize metabolic health

2016_full_inf.tab

This dataset contains all of full text, full names and other metadata from ASHG 2016 Poster Presenters including their session and a predicted gender assigned based on their first name. <br><br>I claim absolutely no credit for generating any of the text within (and thank everyone who wrote abstracts for it)! I only claim credit for formatting this into a machine-readable file format. <br

Dietary omega-3 fatty acids aid in the modulation of inflammation and metabolic health

This article focuses on the role of omega-3 fatty acids as precursors for lipid signaling molecules known as oxylipins. Although omega-3 fatty acids are beneficial in autoimmune disorders, inflammatory diseases and heart disease, they are generally underrepresented in the American diet. A literature review confirms that the consumption of omega-3 fatty acids — whether in food sources such as walnuts, flax seeds and fatty fish (including salmon and sardines), or in supplements — is associated with decreased morbidity and mortality. This growing body of evidence, including the results of a recent study of patients with kidney disease, highlights the need to measure omega-3 fatty acids and their oxylipin products as markers of metabolic health and biomarkers of disease. In addition, there is substantial evidence of the need to increase the omega-3 fatty acid content of American diets to optimize metabolic health

Dietary omega-3 fatty acids aid in the modulation of inflammation and metabolic health

This article focuses on the role of omega-3 fatty acids as precursors for lipid signaling molecules known as oxylipins. Although omega-3 fatty acids are beneficial in autoimmune disorders, inflammatory diseases and heart disease, they are generally underrepresented in the American diet. A literature review confirms that the consumption of omega-3 fatty acids — whether in food sources such as walnuts, flax seeds and fatty fish (including salmon and sardines), or in supplements — is associated with decreased morbidity and mortality. This growing body of evidence, including the results of a recent study of patients with kidney disease, highlights the need to measure omega-3 fatty acids and their oxylipin products as markers of metabolic health and biomarkers of disease. In addition, there is substantial evidence of the need to increase the omega-3 fatty acid content of American diets to optimize metabolic health

High rate of adaptation of mammalian proteins that interact with <i>Plasmodium</i> and related parasites

<div><p><i>Plasmodium</i> parasites, along with their Piroplasm relatives, have caused malaria-like illnesses in terrestrial mammals for millions of years. Several <i>Plasmodium</i>-protective alleles have recently evolved in human populations, but little is known about host adaptation to blood parasites over deeper evolutionary timescales. In this work, we analyze mammalian adaptation in ~500 <i>Plasmodium</i>- or Piroplasm- interacting proteins (PPIPs) manually curated from the scientific literature. We show that (i) PPIPs are enriched for both immune functions and pleiotropy with other pathogens, and (ii) the rate of adaptation across mammals is significantly elevated in PPIPs, compared to carefully matched control proteins. PPIPs with high pathogen pleiotropy show the strongest signatures of adaptation, but this pattern is fully explained by their immune enrichment. Several pieces of evidence suggest that blood parasites specifically have imposed selection on PPIPs. First, even non-immune PPIPs that lack interactions with other pathogens have adapted at twice the rate of matched controls. Second, PPIP adaptation is linked to high expression in the liver, a critical organ in the parasite life cycle. Finally, our detailed investigation of alpha-spectrin, a major red blood cell membrane protein, shows that domains with particularly high rates of adaptation are those known to interact specifically with <i>P</i>. <i>falciparum</i>. Overall, we show that host proteins that interact with <i>Plasmodium</i> and Piroplasm parasites have experienced elevated rates of adaptation across mammals, and provide evidence that some of this adaptation has likely been driven by blood parasites.</p></div

Highly adaptive PPIPs have high expression in the liver.

<p>For both PPIPs and controls matched for total expression, the 5% of the gene set with the most adaptive codons (averaged across all branches) was compared to the remainder of the gene set. Expression is plotted as log₂(GTEx median RPKM + 1) for each set of genes and tissue. For matched controls, highly adaptive genes are expressed at low levels in all malaria-relevant tissues. This pattern differs for PPIPs, particularly in the liver. Significance was determined with the KS test. *** = p<0.001; ** = p <0.01, * = p <0.05; NS = not significant.</p

Top 20 GO functions enriched for PPIPs.

<p>Top 20 GO functions enriched for PPIPs.</p

PPIPs have experienced a significant excess of adaptive substitutions in mammals.

<p>All comparisons are made between PPIPs and carefully matched control proteins (<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1007023#sec013" target="_blank">Methods</a>, Permutation Tests). <b>(a)</b> Evolutionary constraint across great apes, as measured by the ratio of non-synonymous to synonymous polymorphisms, is equivalent in PPIPs and matched controls. The thick red line represents the cumulative density of pN/(pS+1) for PPIPs, whereas the cloud of thin blue lines represents the cumulative densities of 100 sets of matched controls. <b>(b)</b> Across 24 mammal species, the ratio of non-synonymous to synonymous substitutions is elevated in PPIPs versus matched controls. Lines as in (a). <b>(c)</b> BUSTED detects mammalian adaptation in 37% of PPIPs and, on average, 24% of matched controls. Error bars indicate the 95% range of the proportion of matched control genes with evidence of BUSTED adaptation, over 100 sets of matched controls. <b>(d)</b> Across the mammalian phylogeny (<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1007023#pgen.1007023.g001" target="_blank">Fig 1</a>), BS-REL tests identify PPIPs as evolving adaptively on a higher number of branches. Lines as in (a). <b>(e)</b> BS-REL tests identify a higher proportion of codons in PPIPs as evolving adaptively. Adaptive codons per gene are given as an average across all branches. Lines as in (a). <b>(f)</b> The ratio of adaptive codons in PPIPs versus matched controls increases (p = 7x10^-5) as the BUSTED threshold for including BS-REL estimates becomes more stringent. The solid line indicates the mean excess; the dashed line indicates the 1:1 expectation; gray shading indicates 95% confidence intervals. In all panels, *** = p<0.001; NS = p>0.05.</p