Discriminating antigen and non-antigen using proteome dissimilarity II:viral and fungal antigens

Immunogenicity arises via many synergistic mechanisms, yet the overall dissimilarity of pathogenic proteins versus the host proteome has been proposed as a key arbiter. We have previously explored this concept in relation to Bacterial antigens; here we extend our analysis to antigens of viral and fungal origin. Sets of known viral and fungal antigenic and non-antigenic protein sequences were compared to human and mouse proteomes. Both antigenic and non-antigenic sequences lacked human or mouse homologues. Observed distributions were compared using the non-parametric Mann-Whitney test. The statistical null hypothesis was accepted, indicating that antigen and non-antigens did not differ significantly. Likewise, we could not determine a threshold able meaningfully to separate non-antigen from antigen. We conclude that viral and fungal antigens cannot be predicted from pathogen genomes based solely on their dissimilarity to mammalian genomes.

A novel multilocus sequence typing scheme for the opportunistic pathogen Propionibacterium acnes and characterisation of type 1 cell surface-associated antigens

We have developed a novel multilocus sequence typing (MLST) scheme and database (http://pubmlst.org/pacnes/) for Propionibacterium acnes based on the analysis of seven core housekeeping genes. The scheme, which was validated against previously described antibody, single locus and random amplification of polymorphic DNA typing methods, displayed excellent resolution and differentiated 123 isolates into 37 sequence types (STs). An overall clonal population structure was detected with six eBURST groups representing the major clades I, II and III, along with two singletons. Two highly successful and global clonal lineages, ST6 (type IA) and ST10 (type IB1), representing 64?% of this current MLST isolate collection were identified. The ST6 clone and closely related single locus variants, which comprise a large clonal complex CC6, dominated isolates from patients with acne, and were also significantly associated with ophthalmic infections. Our data therefore support an association between acne and P. acnes strains from the type IA cluster and highlight the role of a widely disseminated clonal genotype in this condition. Characterization of type I cell surface-associated antigens that are not detected in ST10 or strains of type II and III identified two dermatan-sulphate-binding proteins with putative phase/antigenic variation signatures. We propose that the expression of these proteins by type IA organisms contributes to their role in the pathophysiology of acne and helps explain the recurrent nature of the disease. The MLST scheme and database described in this study should provide a valuable platform for future epidemiological and evolutionary studies of P. acnes.

Noise characterization and transmission evaluation of unrepeated Raman amplified DP-16QAM link

Impairments characterization and performance evaluation of Raman amplified unrepeated DP-16QAM transmissions are conducted. Experimental results indicate that small gain in forward direction enhance the system signal-to-noise ratio for longer reach without introducing noticeable penalty.

Identification of the HLA-DM/HLA-DR interface

Human leukocyte antigen (HLA)-DM is a critical participant in antigen presentation that catalyzes the dissociation of the Class II-associated Invariant chain-derived Peptide (CLIP) from the major histocompatibility complex (MHC) Class II molecules. There is competition amongst peptides for access to an MHC Class II groove and it has been hypothesised that DM functions as a 'peptide editor' that catalyzes the replacement of one peptide for another within the groove. It is established that the DM catalyst interacts directly with the MHC Class II but the precise location of the interface is unknown. Here, we combine previously described mutational data with molecular docking and energy minimisation simulations to identify a putative interaction site of >4000A2 which agrees with known point mutational data for both the DR and DM molecule. The docked structure is validated by comparison with experimental data and previously determined properties of protein-protein interfaces. A possible dissociation mechanism is suggested by the presence of an acidic cluster near the N terminus of the bound peptide.

73.7 Tb/s (96 x 3 x 256-Gb/s) mode-division-multiplexed DP-16QAM transmission with inline MM-EDFA

Transmission of a 73.7 Tb/s (96x3x256-Gb/s) DP-16QAM mode-division-multiplexed signal over 119km of few-mode fiber transmission line incorporating an inline multi mode EDFA and a phase plate based mode (de-)multiplexer is demonstrated. Data-aided 6x6 MIMO digital signal processing was used to demodulate the signal. The total demonstrated net capacity, taking into account 20% of FEC-overhead and 7.5% additional overhead (Ethernet and training sequences), is 57.6 Tb/s, corresponding to a spectral efficiency of 12 bits/s/Hz.

Mode-division-multiplexed 3x112-Gb/s DP-QPSK transmission over 80 km few-mode fiber with inline MM-EDFA and blind DSP

We show transmission of a 3x112-Gb/s DP-QPSK mode-division-multiplexed signal up to 80km, with and without multi-mode EDFA, using blind 6x6 MIMO digital signal processing. We show that the OSNR-penalty induced by mode-mixing in the multi-mode EDFA is negligible.

1THz-bandwidth polarization-diverse optical phase conjugation of 10x114Gb/s DP-QPSK WDM signals

Polarization diverse optical phase conjugation of a 1THz spectral-band 1.14Tb/s DP-QPSK WDM multiplex is demonstrated for the first time, showing a worst case Q2 penalty of 0.9dB over all conjugate wavelengths, polarizations and OSNR. © 2014 OSA.

The classification of HLA supertypes by GRID/CPCA and hierarchical clustering methods

Biological experiments often produce enormous amount of data, which are usually analyzed by data clustering. Cluster analysis refers to statistical methods that are used to assign data with similar properties into several smaller, more meaningful groups. Two commonly used clustering techniques are introduced in the following section: principal component analysis (PCA) and hierarchical clustering. PCA calculates the variance between variables and groups them into a few uncorrelated groups or principal components (PCs) that are orthogonal to each other. Hierarchical clustering is carried out by separating data into many clusters and merging similar clusters together. Here, we use an example of human leukocyte antigen (HLA) supertype classification to demonstrate the usage of the two methods. Two programs, Generating Optimal Linear Partial Least Square Estimations (GOLPE) and Sybyl, are used for PCA and hierarchical clustering, respectively. However, the reader should bear in mind that the methods have been incorporated into other software as well, such as SIMCA, statistiXL, and R.

VaxiJen:a server for prediction of protective antigens, tumour antigens and subunit vaccines

Background - Vaccine development in the post-genomic era often begins with the in silico screening of genome information, with the most probable protective antigens being predicted rather than requiring causative microorganisms to be grown. Despite the obvious advantages of this approach – such as speed and cost efficiency – its success remains dependent on the accuracy of antigen prediction. Most approaches use sequence alignment to identify antigens. This is problematic for several reasons. Some proteins lack obvious sequence similarity, although they may share similar structures and biological properties. The antigenicity of a sequence may be encoded in a subtle and recondite manner not amendable to direct identification by sequence alignment. The discovery of truly novel antigens will be frustrated by their lack of similarity to antigens of known provenance. To overcome the limitations of alignment-dependent methods, we propose a new alignment-free approach for antigen prediction, which is based on auto cross covariance (ACC) transformation of protein sequences into uniform vectors of principal amino acid properties. Results - Bacterial, viral and tumour protein datasets were used to derive models for prediction of whole protein antigenicity. Every set consisted of 100 known antigens and 100 non-antigens. The derived models were tested by internal leave-one-out cross-validation and external validation using test sets. An additional five training sets for each class of antigens were used to test the stability of the discrimination between antigens and non-antigens. The models performed well in both validations showing prediction accuracy of 70% to 89%. The models were implemented in a server, which we call VaxiJen. Conclusion - VaxiJen is the first server for alignment-independent prediction of protective antigens. It was developed to allow antigen classification solely based on the physicochemical properties of proteins without recourse to sequence alignment. The server can be used on its own or in combination with alignment-based prediction methods.

1.14Tb/s DP-QPSK WDM polarization-diverse optical phase conjugation

Optical phase conjugation (OPC) of a polarization-multiplexed comb of 10x114Gb/s DP-QPSK signals has been demonstrated for the first time, occupying a spectral bandwidth of >1THz (~9nm). The nonlinear element employed for the OPC was highly nonlinear fiber (HNLF) optimized for the suppression of stimulated Brillouin scattering (SBS) and configured in a bi-directional loop offering polarization diversity. Pump power (each way about the loop) and input signal power to the OPC subsystem were optimized at 29.7dBm and + 3dBm respectively producing a Q2 penalty of ≤0.9dB over all conjugate wavelengths, polarizations and output OSNR (up to 20dB).

73.7 Tb/s (96X3x256-Gb/s) mode-division-multiplexed DP-16QAM transmission with inline MM-EDFA

We show transmission of a 73.7 Tb/s (96x3x256-Gb/s) DP-16QAM modedivision- multiplexed signal over 119km of few-mode fiber with inline multi-mode EDFA, using 6x6 MIMO digital signal processing. The total demonstrated net capacity is 57.6 Tb/s (SE 12 bits/s/Hz). © 2012 OSA.

Transmission comparison of ultra-long Raman fibre laser based amplification with first and dual order Raman amplification using 10×118 Gbit/s DP-QPSK

Experimental investigations of 10×118 Gbit/s DP-QPSK WDM transmission using three types of distributed Raman amplification techniques are presented. Novel ultra-long Raman fibre laser based amplification with second order counter-propagated pumping is compared with conventional first order and dual order counter-pumped Raman amplification. We demonstrate that URFL based amplification can extend the transmission reach up to a distance of 7520 km in comparison with 5010 km and 6180 km using first order and dual order Raman amplification respectively. © 2014 IEEE.

112Gbit/s RF assisted dual-carrier DP-16-QAM in installed and new build WDM applications

The performance of a 112Gbit/s dual-carrier DP-16-QAM channel in various WDM configurations is characterized. Variations of the dispersion map, ROADM count and system length are experimentally evaluated and compared with numerical simulation. © 2012 OSA.

Peptide binding to the HLA-DRB1 supertype:a proteochemometrics analysis

A proteochemometrics approach was applied to a set of 2666 peptides binding to 12 HLA-DRB1 proteins. Sequences of both peptide and protein were described using three z-descriptors. Cross terms accounting for adjacent positions and for every second position in the peptides were included in the models, as well as cross terms for peptide/protein interactions. Models were derived based on combinations of different blocks of variables. These models had moderate goodness of fit, as expressed by r2, which ranged from 0.685 to 0.732; and good cross-validated predictive ability, as expressed by q2, which varied from 0.678 to 0.719. The external predictive ability was tested using a set of 356 HLA-DRB1 binders, which showed an r2(pred) in the range 0.364-0.530. Peptide and protein positions involved in the interactions were analyzed in terms of hydrophobicity, steric bulk and polarity.

Large-scale molecular dynamics simulations of HLA-A*0201 complexed with a tumor-specific antigenic peptide:can the α3 and β2m domains be neglected?

Large-scale massively parallel molecular dynamics (MD) simulations of the human class I major histo-compatibility complex (MHC) protein HLA-A*0201 bound to a decameric tumor-specific antigenic peptide GVY-DGREHTV were performed using a scalable MD code on high-performance computing platforms. Such computational capabilities put us in reach of simulations of various scales and complexities. The supercomputing resources available Large-scale massively parallel molecular dynamics (MD) simulations of the human class I major histocompatibility complex (MHC) protein HLA-A*0201 bound to a decameric tumor-specific antigenic peptide GVYDGREHTV were performed using a scalable MD code on high-performance computing platforms. Such computational capabilities put us in reach of simulations of various scales and complexities. The supercomputing resources available for this study allow us to compare directly differences in the behavior of very large molecular models; in this case, the entire extracellular portion of the peptide–MHC complex vs. the isolated peptide binding domain. Comparison of the results from the partial and the whole system simulations indicates that the peptide is less tightly bound in the partial system than in the whole system. From a detailed study of conformations, solvent-accessible surface area, the nature of the water network structure, and the binding energies, we conclude that, when considering the conformation of the α1–α2 domain, the α3 and β2m domains cannot be neglected. © 2004 Wiley Periodicals, Inc. J Comput Chem 25: 1803–1813, 2004