[show abstract][hide abstract] ABSTRACT: Here we assessed the use of domain families for predicting the functions of whole proteins. These 'functional families' (FunFams) were derived using a protocol that combines sequence clustering with supervised cluster evaluation, relying on available high-quality Gene Ontology (GO) annotation data in the latter step. In essence, the protocol groups domain sequences belonging to the same superfamily into families based on the GO annotations of their parent proteins. An initial test based on enzyme sequences confirmed that the FunFams resemble enzyme (domain) families much better than do families produced by sequence clustering alone. For the CAFA 2011 experiment, we further associated the FunFams with GO terms probabilistically. All target proteins were first submitted to domain superfamily assignment, followed by FunFam assignment and, eventually, function assignment. The latter included an integration step for multi-domain target proteins. The CAFA results put our domain-based approach among the top ten of 31 competing groups and 56 prediction methods, confirming that it outperforms simple pairwise whole-protein sequence comparisons.
[show abstract][hide abstract] ABSTRACT: Many Automatic Function Prediction (AFP) methods were developed to cope with an increasing growth of the number of gene sequences that are available from high throughput sequencing experiments. To support the development of AFP methods, it is essential to have community wide experiments for evaluating performance of existing AFP methods. Critical Assessment of Function Annotation (CAFA) is one such community experiment. The meeting of CAFA was held as a Special Interest Group (SIG) meeting at the Intelligent Systems in Molecular Biology (ISMB) conference in 2011. Here, we perform a detailed analysis of two sequence-based function prediction methods, PFP and ESG, which were developed in our lab, using the predictions submitted to CAFA.
We evaluate PFP and ESG using four different measures in comparison with BLAST, Prior, and GOtcha. In addition to the predictions submitted to CAFA, we further investigate performance of a different scoring function to rank order predictions by PFP as well as PFP/ESG predictions enriched with Priors that simply adds frequently occurring Gene Ontology terms as a part of predictions. Prediction accuracies of each method were also evaluated separately for different functional categories. Successful and unsuccessful predictions by PFP and ESG are also discussed in comparison with BLAST.
The in-depth analysis discussed here will complement the overall assessment by the CAFA organizers. Since PFP and ESG are based on sequence database search results, our analyses are not only useful for PFP and ESG users but will also shed light on the relationship of the sequence similarity space and functions that can be inferred from the sequences.
[show abstract][hide abstract] ABSTRACT: Although the ultrastructure of the schistosome esophageal gland was described >35 years ago, its role in the processing of ingested blood has never been established. The current study was prompted by our identification of MEG-4.1 expression in the gland and the observation of erythrocyte uncoating in the posterior esophagus.
The salient feature of the posterior esophagus, characterized by confocal and electron microscopy, is the enormous increase in membrane surface area provided by the plate-like extensions and basal invaginations of the lining syncytium, with unique crystalloid vesicles releasing their contents between the plates. The feeding process was shown by video microscopy to be divided into two phases, blood first accumulating in the anterior lumen before passing as a bolus to the posterior. There it streamed around a plug of material revealed by confocal microscopy as tethered leucocytes. These were present in far larger numbers than predicted from the volume of the lumen, and in varying states of damage and destruction. Intact erythrocytes were detected in the anterior esophagus but not observed thereafter, implying that their lysis occurred rapidly as they enter the posterior. Two further genes, MEGs 4.2 and 14, were shown to be expressed exclusively in the esophageal gland. Bioinformatics predicted that MEGs 4.1 and 4.2 possessed a common hydrophobic region with a shared motif, while antibodies to SjMEG-4.1 showed it was bound to leucocytes in the esophageal lumen. It was also predicted that MEGs 4.1 and 14 were heavily O-glycosylated and this was confirmed for the former by 2D-electrophoresis and Western blotting.
The esophageal gland and its products play a central role in the processing of ingested blood. The binding of host antibodies in the esophageal lumen shows that some constituents are antibody targets and could provide a new source of vaccine candidates.
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