PRED(TAP): a system for prediction of peptide binding to the human transporter associated with antigen processing

BACKGROUND: The transporter associated with antigen processing (TAP) is a critical component of the major histocompatibility complex (MHC) class I antigen processing and presentation pathway. TAP transports antigenic peptides into the endoplasmic reticulum where it loads them into the binding groove of MHC class I molecules. Because peptides must first be transported by TAP in order to be presented on MHC class I, TAP binding preferences should impact significantly on T-cell epitope selection. DESCRIPTION: PRED(TAP )is a computational system that predicts peptide binding to human TAP. It uses artificial neural networks and hidden Markov models as predictive engines. Extensive testing was performed to valid the prediction models. The results showed that PRED(TAP )was both sensitive and specific and had good predictive ability (area under the receiver operating characteristic curve Aroc>0.85). CONCLUSION: PRED(TAP )can be integrated with prediction systems for MHC class I binding peptides for improved performance of in silico prediction of T-cell epitopes. PRED(TAP )is available for public use at [1]

Contact Stress Prediction Model for Variable Hyperbolic Circular Arc Gear Based on the Optimized Kriging-Response Surface Model

In order to study the influence of design parameters (pressure angle, tooth width, tooth line radius, modulus, and moment) on contact stress of variable hyperbolic circular arc gear (VHCAG) and to obtain the best manufacturing parameters, The Kriging-Response Surface Model, a hybrid surrogate model with adaptive quantum particle swarm optimization (QPSO) algorithm was proposed to establish the expression prediction model for the relation between design parameters and contact stress. An intelligent quantum particle swarm optimization algorithm based on adaptive weight and natural selection is proposed to optimize the parameters of Gaussian variation function of the kriging surrogate model to improve its fitting accuracy. The global search ability of quantum particles is improved, and the accuracy and stability of the algorithm are improved by adjusting the weight of quantum particles adaptively and by optimizing the elimination iteration process, and the response relationship between design parameters and contact stress was established. The binomial response surface model of gear design parameters and contact stress is established based on the output obtained through the improved kriging model; this simplifies the complex expression of the kriging model. The effects of parameters and their cross-terms on contact stress are analysed based on the contact stress prediction model established by using the optimized Kriging-Response Surface Model hybrid surrogate model. The hybrid Kriging-Response Surface Model surrogate model lays a foundation for the research on the reliability and robust optimization of cylindrical gears with variable hyperbolic arc tooth profile

Big Data Analytics in Immunology: A Knowledge-Based Approach

With the vast amount of immunological data available, immunology research is entering the big data era. These data vary in granularity, quality, and complexity and are stored in various formats, including publications, technical reports, and databases. The challenge is to make the transition from data to actionable knowledge and wisdom and bridge the knowledge gap and application gap. We report a knowledge-based approach based on a framework called KB-builder that facilitates data mining by enabling fast development and deployment of web-accessible immunological data knowledge warehouses. Immunological knowledge discovery relies heavily on both the availability of accurate, up-to-date, and well-organized data and the proper analytics tools. We propose the use of knowledge-based approaches by developing knowledgebases combining well-annotated data with specialized analytical tools and integrating them into analytical workflow. A set of well-defined workflow types with rich summarization and visualization capacity facilitates the transformation from data to critical information and knowledge. By using KB-builder, we enabled streamlining of normally time-consuming processes of database development. The knowledgebases built using KB-builder will speed up rational vaccine design by providing accurate and well-annotated data coupled with tailored computational analysis tools and workflow

Protomelission is an early dasyclad alga and not a Cambrian bryozoan

The animal phyla and their associated body plans originate from a singular burst of evolution occurring during the Cambrian period, over 500 million years ago1. The phylum Bryozoa, the colonial ‘moss animals’, have been the exception: convincing skeletons of this biomineralizing clade have been absent from Cambrian strata, in part because potential bryozoan fossils are difficult to distinguish from the modular skeletons of other animal and algal groups2,3. At present, the strongest candidate4 is the phosphatic microfossil Protomelission5. Here we describe exceptionally preserved non-mineralized anatomy in Protomelission-like macrofossils from the Xiaoshiba Lagerstätte6. Taken alongside the detailed skeletal construction and the potential taphonomic origin of ‘zooid apertures’, we consider that Protomelission is better interpreted as the earliest dasycladalean green alga—emphasizing the ecological role of benthic photosynthesizers in early Cambrian communities. Under this interpretation, Protomelission cannot inform the origins of the bryozoan body plan; despite a growing number of promising candidates7,8,9, there remain no unequivocal bryozoans of Cambrian age

FLAVIdB: A data mining system for knowledge discovery in flaviviruses with direct applications in immunology and vaccinology

BACKGROUND: The flavivirus genus is unusually large, comprising more than 70 species, of which more than half are known human pathogens. It includes a set of clinically relevant infectious agents such as dengue, West Nile, yellow fever, and Japanese encephalitis viruses. Although these pathogens have been studied extensively, safe and efficient vaccines lack for the majority of the flaviviruses. RESULTS: We have assembled a database that combines antigenic data of flaviviruses, specialized analysis tools, and workflows for automated complex analyses focusing on applications in immunology and vaccinology. FLAVIdB contains 12,858 entries of flavivirus antigen sequences, 184 verified T-cell epitopes, 201 verified B-cell epitopes, and 4 representative molecular structures of the dengue virus envelope protein. FLAVIdB was assembled by collection, annotation, and integration of data from GenBank, GenPept, UniProt, IEDB, and PDB. The data were subject to extensive quality control (redundancy elimination, error detection, and vocabulary consolidation). Further annotation of selected functionally relevant features was performed by organizing information extracted from the literature. The database was incorporated into a web-accessible data mining system, combining specialized data analysis tools for integrated analysis of relevant data categories (protein sequences, macromolecular structures, and immune epitopes). The data mining system includes tools for variability and conservation analysis, T-cell epitope prediction, and characterization of neutralizing components of B-cell epitopes. FLAVIdB is accessible at cvc.dfci.harvard.edu/flavi/ CONCLUSION: FLAVIdB represents a new generation of databases in which data and tools are integrated into a data mining infrastructures specifically designed to aid rational vaccine design by discovery of vaccine targets

New multipodomerous appendages of stem-group euarthropods from the Cambrian (Stage 4) Guanshan Konservat-Lagerstätte.

Funder: Museum of Comparative Zoology, Harvard UniversityFunder: Herchel Smith Postdoctoral FellowshipStem-group euarthropods are important for understanding the early evolutionary and ecological history of the most species-rich animal phylum on Earth. Of particular interest are fossil taxa that occupy a phylogenetic position immediately crownwards of radiodonts, for this part of the euarthropod tree is associated with the appearance of several morphological features that characterize extant members of the group. Here, we report two new euarthropods from the Cambrian Stage 4 Guanshan Biota of South China. The fuxianhuiid Alacaris? sp. is represented by isolated appendages composed of a gnathobasic protopodite and an endite-bearing endopod of at least 20 podomeres. This material represents the youngest occurrence of the family Chengjiangocarididae, and its first record outside the Chengjiang and Xiaoshiba biotas. We also describe Lihuacaris ferox gen. et sp. nov. based on well-preserved and robust isolated appendages. Lihuacaris ferox exhibits an atypical combination of characters including an enlarged rectangular base, 11 endite-bearing podomeres and a hypertrophied distal element bearing 8-10 curved spines. Alacaris? sp. appendages display adaptations for macrophagy. Lihuacaris ferox appendages resemble the frontal appendages of radiodonts, as well as the post-oral endopods of chengjiangocaridid fuxianhuids and other deuteropods with well-documented raptorial/predatory habits. Lihuacaris ferox contributes towards the record of endemic biodiversity in the Guanshan Biota

Pathway analysis and transcriptomics improve protein identification by shotgun proteomics from samples comprising small number of cells - a benchmarking study

BACKGROUND: Proteomics research is enabled with the high-throughput technologies, but our ability to identify expressed proteome is limited in small samples. The coverage and consistency of proteome expression are critical problems in proteomics. Here, we propose pathway analysis and combination of microproteomics and transcriptomics analyses to improve mass-spectrometry protein identification from small size samples. RESULTS: Multiple proteomics runs using MCF-7 cell line detected 4,957 expressed proteins. About 80% of expressed proteins were present in MCF-7 transcripts data; highly expressed transcripts are more likely to have expressed proteins. Approximately 1,000 proteins were detected in each run of the small sample proteomics. These proteins were mapped to gene symbols and compared with gene sets representing canonical pathways, more than 4,000 genes were extracted from the enriched gene sets. The identified canonical pathways were largely overlapping between individual runs. Of identified pathways 182 were shared between three individual small sample runs. CONCLUSIONS: Current technologies enable us to directly detect 10% of expressed proteomes from small sample comprising as few as 50 cells. We used knowledge-based approaches to elucidate the missing proteome that can be verified by targeted proteomics. This knowledge-based approach includes pathway analysis and combination of gene expression and protein expression data for target prioritization. Genes present in both the enriched gene sets (canonical pathways collection) and in small sample proteomics data correspond to approximately 50% of expressed proteomes in larger sample proteomics data. In addition, 90% of targets from canonical pathways were estimated to be expressed. The comparison of proteomics and transcriptomics data, suggests that highly expressed transcripts have high probability of protein expression. However, approximately 10% of expressed proteins could not be matched with the expressed transcripts.The cost of this publication was funded by Vladimir Brusic. (Vladimir Brusic)Published versio

PRED(BALB/c): a system for the prediction of peptide binding to H2(d) molecules, a haplotype of the BALB/c mouse

PRED(BALB/c) is a computational system that predicts peptides binding to the major histocompatibility complex-2 (H2(d)) of the BALB/c mouse, an important laboratory model organism. The predictions include the complete set of H2(d) class I (H2-K(d), H2-L(d) and H2-D(d)) and class II (I-E(d) and I-A(d)) molecules. The prediction system utilizes quantitative matrices, which were rigorously validated using experimentally determined binders and non-binders and also by in vivo studies using viral proteins. The prediction performance of PRED(BALB/c) is of very high accuracy. To our knowledge, this is the first online server for the prediction of peptides binding to a complete set of major histocompatibility complex molecules in a model organism (H2(d) haplotype). PRED(BALB/c) is available at

Tandem duplication, circular permutation, molecular adaptation: how Solanaceae resist pests via inhibitors

<p>Abstract</p> <p>Background</p> <p>The Potato type II (Pot II) family of proteinase inhibitors plays critical roles in the defense system of plants from <it>Solanaceae </it>family against pests. To better understand the evolution of this family, we investigated the correlation between sequence and structural repeats within this family and the evolution and molecular adaptation of Pot II genes through computational analysis, using the putative ancestral domain sequence as the basic repeat unit.</p> <p>Results</p> <p>Our analysis discovered the following interesting findings in Pot II family. (1) We classified the structural domains in Pot II family into three types (original repeat domain, circularly permuted domain, the two-chain domain) according to the existence of two linkers between the two domain components, which clearly show the circular permutation relationship between the original repeat domain and circularly permuted domain. (2) The permuted domains appear more stable than original repeat domain, from available structural information. Therefore, we proposed a multiple-repeat sequence is likely to adopt the permuted domain from contiguous sequence segments, with the N- and C-termini forming a single non-contiguous structural domain, linking the bracelet of tandem repeats. (3) The analysis of nonsynonymous/synonymous substitution rates ratio in Pot II domain revealed heterogeneous selective pressures among amino acid sites: the reactive site is under positive Darwinian selection (providing different specificity to target varieties of proteinases) while the cysteine scaffold is under purifying selection (essential for maintaining the fold). (4) For multi-repeat Pot II genes from <it>Nicotiana </it>genus, the proteolytic processing site is under positive Darwinian selection (which may improve the cleavage efficiency).</p> <p>Conclusion</p> <p>This paper provides comprehensive analysis and characterization of Pot II family, and enlightens our understanding on the strategies (Gene and domain duplication, structural circular permutation and molecular adaptation) of <it>Solanaceae </it>plants for defending pathogenic attacks through the evolution of Pot II genes.</p