Camostat Does Not Inhibit the Proteolytic Activity of Neutrophil Serine Proteases.

Coronavirus disease 2019 (COVID-19) can lead to multi-organ failure influenced by comorbidities and age. Binding of the severe acute respiratory syndrome coronavirus 2 spike protein (SARS-CoV-2 S protein) to angiotensin-converting enzyme 2 (ACE2), along with proteolytic digestion of the S protein by furin and transmembrane protease serine subtype 2 (TMPRSS2), provokes internalization of SARS-CoV-2 into the host cell. Productive infection occurs through viral replication in the cytosol and cell-to-cell transmission. The catalytic activity of TMPRSS2 can be blocked by the trypsin-like serine protease inhibitor camostat, which impairs infection by SARS-CoV-2. At the site of infection, immune cells, such as neutrophils, infiltrate and become activated, releasing neutrophil serine proteases (NSPs), including cathepsin G (CatG), neutrophil elastase (NE), and proteinase 3 (PR3), which promote the mounting of a robust immune response. However, NSPs might be involved in infection and the severe outcome of COVID-19 since the uncontrolled proteolytic activity is responsible for many complications, including autoimmunity, chronic inflammatory disorders, cardiovascular diseases, and thrombosis. Here, we demonstrate that camostat does not inhibit the catalytic activity of CatG, NE, and PR3, indicating the need for additional selective serine protease inhibitors to reduce the risk of developing severe COVID-19.

APBioNet's annual International Conference on Bioinformatics (InCoB) returns to India in 2018.

InCoB, one of the largest annual bioinformatics conferences in the Asia-Pacific region since its launch in 2002, returned to New Delhi, India after 12 years, with a conference attendance of 314 delegates. The 2018 conference had sessions on Big Data and Algorithms, Next Generation Sequencing and Omics Science, Structure, Function and Interactions, Disease and Drug Discovery and Plant and Agricultural Bioinformatics. The conference also featured an industry track as well as panel discussions on Women in Bioinformatics and Democratization vs. Quality control in academic publishing. Asia Pacific Bioinformatics Interaction & Networking Society (APbians) was launched as an APBionet Special Interest Group. Of the 52 oral presentations made, 22 were accepted in supplemental issues of BMC Bioinformatics, BMC Genomics or BMC Medical Genomics and are briefly reviewed here. Next year's InCoB will be held in Jakarta, Indonesia from September 10-12, 2019.

Top soil physical and chemical properties in Kazakhstan across a north-south gradient.

Kazakhstan's soil properties have yet to be comprehensively characterized. We sampled 40 sites consisting of ten major soil types at spring (wet) and late-summer (dry) seasons. The sample locations range from semi-arid to arid with an annual mean air temperature from 1.2 to 10.7 °C and annual precipitation from less than 200 to around 400 mm. Overall topsoil total (STC), organic (SOC), and inorganic (SIC) carbon did not change significantly between spring and late summer. STC and SOC show a wave like pattern from north to south with two maxima in northern and southern Kazakhstan and one minimum in central Kazakhstan. With a few exceptions SIC content at northern sites is generally low, whereas at Lake Balkhash SIC can exceed 75% of STC. Independent of the seasons, SOC significantly differed among soil types. Total nitrogen content distribution among our sampling sites followed a similar pattern as SOC with significant differences between soil types occurring in northern, central and southern Kazakhstan.

A bioinformatics potpourri.

The 16th International Conference on Bioinformatics (InCoB) was held at Tsinghua University, Shenzhen from September 20 to 22, 2017. The annual conference of the Asia-Pacific Bioinformatics Network featured six keynotes, two invited talks, a panel discussion on big data driven bioinformatics and precision medicine, and 66 oral presentations of accepted research articles or posters. Fifty-seven articles comprising a topic assortment of algorithms, biomolecular networks, cancer and disease informatics, drug-target interactions and drug efficacy, gene regulation and expression, imaging, immunoinformatics, metagenomics, next generation sequencing for genomics and transcriptomics, ontologies, post-translational modification, and structural bioinformatics are the subject of this editorial for the InCoB2017 supplement issues in BMC Genomics, BMC Bioinformatics, BMC Systems Biology and BMC Medical Genomics. New Delhi will be the location of InCoB2018, scheduled for September 26-28, 2018.

Effects of a Single Escape Mutation on T Cell and HIV-1 Co-adaptation.

The mechanistic basis for the progressive accumulation of Y(135)F Nef mutant viruses in the HIV-1-infected population remains poorly understood. Y(135)F viruses carry the 2F mutation within RW8 and RF10, which are two HLA-A(∗)24:02-restricted superimposed Nef epitopes recognized by distinct and adaptable CD8(+) T cell responses. We combined comprehensive analysis of the T cell receptor repertoire and cross-reactive potential of wild-type or 2F RW8- and RF10-specific CD8(+) T cells with peptide-MHC complex stability and crystal structure studies. We find that, by affecting direct and water-mediated hydrogen bond networks within the peptide-MHC complex, the 2F mutation reduces both TCR and HLA binding. This suggests an advantage underlying the evolution of the 2F variant with decreased CD8(+) T cell efficacy. Our study provides a refined understanding of HIV-1 and CD8(+) T cell co-adaptation at the population level.

2016 update on APBioNet's annual international conference on bioinformatics (InCoB).

InCoB became since its inception in 2002 one of the largest annual bioinformatics conferences in the Asia-Pacific region with attendance ranging between 150 and 250 delegates depending on the venue location. InCoB 2016 in Singapore was attended by almost 220 delegates. This year, sessions on structural bioinformatics, sequence and sequencing, and next-generation sequencing fielded the highest number of oral presentation. Forty-four out 96 oral presentations were associated with an accepted manuscript in supplemental issues of BMC Bioinformatics, BMC Genomics, BMC Medical Genomics or BMC Systems Biology. Articles with a genomics focus are reviewed in this editorial. Next year's InCoB will be held in Shenzen, China from September 20 to 22, 2017.

Bioinformatics and systems biology research update from the 15th International Conference on Bioinformatics (InCoB2016).

The International Conference on Bioinformatics (InCoB) has been publishing peer-reviewed conference papers in BMC Bioinformatics since 2006. Of the 44 articles accepted for publication in supplement issues of BMC Bioinformatics, BMC Genomics, BMC Medical Genomics and BMC Systems Biology, 24 articles with a bioinformatics or systems biology focus are reviewed in this editorial. InCoB2017 is scheduled to be held in Shenzen, China, September 20-22, 2017.

GIW and InCoB, two premier bioinformatics conferences in Asia with a combined 40 years of history.

Knowledge discovery in bioinformatics thrives on joint and inclusive efforts of stakeholders. Similarly, knowledge dissemination is expected to be more effective and scalable through joint efforts. Therefore, the International Conference on Bioinformatics (InCoB) and the International Conference on Genome Informatics (GIW) were organized as a joint conference for the first time in 13 years of coexistence. The Asia-Pacific Bioinformatics Network (APBioNet) and the Japanese Society for Bioinformatics (JSBi) collaborated to host GIW/InCoB2015 in Tokyo, September 9-11, 2015. The joint endeavour yielded 51 research articles published in seven journals, 78 poster and 89 oral presentations, showcasing bioinformatics research in the Asia-Pacific region. Encouraged by the results and reduced organizational overheads, APBioNet will collaborate with other bioinformatics societies in organizing co-located bioinformatics research and training meetings in the future. InCoB2016 will be hosted in Singapore, September 21-23, 2016.

GIW and InCoB are advancing bioinformatics in the Asia-Pacific.

GIW/InCoB2015 the joint 26th International Conference on Genome Informatics (GIW) and 14th International Conference on Bioinformatics (InCoB) held in Tokyo, September 9-11, 2015 was attended by over 200 delegates. Fifty-one out of 89 oral presentations were based on research articles accepted for publication in four BMC journal supplements and three other journals. Sixteen articles in this supplement and six articles in the BMC Systems Biology GIW/InCoB2015 Supplement are covered by this introduction. The topics range from genome informatics, protein structure informatics, image analysis to biological networks and biomarker discovery.

InCoB2014: bioinformatics to tackle the data to knowledge challenge. Introduction.

Since 2006, the International Conference on Bioinformatics (InCoB) has been publishing selected papers in BMC Bioinformatics. Papers within the scope of the journal from the 13th InCoB July 31-2 August, 2014 in Sydney, Australia have been compiled in this supplement. These span protein and proteome informatics, structural bioinformatics, software development and bioimaging to pharmacoinformatics and disease informatics, representing the breadth of bioinformatics research in the Asia-Pacific.

InCoB2014: mining biological data from genomics for transforming industry and health.

The 13th International Conference on Bioinformatics (InCoB2014) was held for the first time in Australia, at Sydney, July 31-2 August, 2014. InCoB is the annual scientific gathering of the Asia-Pacific Bioinformatics Network (APBioNet), hosted since 2002 in the Asia-Pacific region. Of 106 full papers submitted to the BMC track of InCoB2014, 50 (47.2%) were accepted in BMC Bioinformatics, BMC Genomics and BMC Systems Biology supplements, with three papers in a new BMC Medical Genomics supplement. While the majority of presenters and authors were from Asia and Australia, the increasing number of US and European conference attendees augurs well for the international flavour of InCoB. Next year's InCoB will be held jointly with the Genome Informatics Workshop (GIW), September 9-11, 2015 in Tokyo, Japan, with a view to integrate bioinformatics communities in the region.

InCoB2014: Systems Biology update from the Asia-Pacific. Introduction.

Selected papers from the 13th International Conference on Bioinformatics (InCoB2014), July 31-2 August, 2014 in Sydney, Australia have been compiled in this supplement. These range from network analysis and gene regulatory networks to systems level biological analysis, providing the 2014 update to InCoB's computational systems biology research.

BlockLogo: visualization of peptide and sequence motif conservation.

BlockLogo is a web-server application for the visualization of protein and nucleotide fragments, continuous protein sequence motifs, and discontinuous sequence motifs using calculation of block entropy from multiple sequence alignments. The user input consists of a multiple sequence alignment, selection of motif positions, type of sequence, and output format definition. The output has BlockLogo along with the sequence logo, and a table of motif frequencies. We deployed BlockLogo as an online application and have demonstrated its utility through examples that show visualization of T-cell epitopes and B-cell epitopes (both continuous and discontinuous). Our additional example shows a visualization and analysis of structural motifs that determine the specificity of peptide binding to HLA-DR molecules. The BlockLogo server also employs selected experimentally validated prediction algorithms to enable on-the-fly prediction of MHC binding affinity to 15 common HLA class I and class II alleles as well as visual analysis of discontinuous epitopes from multiple sequence alignments. It enables the visualization and analysis of structural and functional motifs that are usually described as regular expressions. It provides a compact view of discontinuous motifs composed of distant positions within biological sequences. BlockLogo is available at: http://research4.dfci.harvard.edu/cvc/blocklogo/ and http://met-hilab.bu.edu/blocklogo/.

Tysnd1 deficiency in mice interferes with the peroxisomal localization of PTS2 enzymes, causing lipid metabolic abnormalities and male infertility.

Peroxisomes are subcellular organelles involved in lipid metabolic processes, including those of very-long-chain fatty acids and branched-chain fatty acids, among others. Peroxisome matrix proteins are synthesized in the cytoplasm. Targeting signals (PTS or peroxisomal targeting signal) at the C-terminus (PTS1) or N-terminus (PTS2) of peroxisomal matrix proteins mediate their import into the organelle. In the case of PTS2-containing proteins, the PTS2 signal is cleaved from the protein when transported into peroxisomes. The functional mechanism of PTS2 processing, however, is poorly understood. Previously we identified Tysnd1 (Trypsin domain containing 1) and biochemically characterized it as a peroxisomal cysteine endopeptidase that directly processes PTS2-containing prethiolase Acaa1 and PTS1-containing Acox1, Hsd17b4, and ScpX. The latter three enzymes are crucial components of the very-long-chain fatty acids ß-oxidation pathway. To clarify the in vivo functions and physiological role of Tysnd1, we analyzed the phenotype of Tysnd1(-/-) mice. Male Tysnd1(-/-) mice are infertile, and the epididymal sperms lack the acrosomal cap. These phenotypic features are most likely the result of changes in the molecular species composition of choline and ethanolamine plasmalogens. Tysnd1(-/-) mice also developed liver dysfunctions when the phytanic acid precursor phytol was orally administered. Phyh and Agps are known PTS2-containing proteins, but were identified as novel Tysnd1 substrates. Loss of Tysnd1 interferes with the peroxisomal localization of Acaa1, Phyh, and Agps, which might cause the mild Zellweger syndrome spectrum-resembling phenotypes. Our data established that peroxisomal processing protease Tysnd1 is necessary to mediate the physiological functions of PTS2-containing substrates.

Computational vaccinology and the ICoVax 2012 workshop.

Computational vaccinology or vaccine informatics is an interdisciplinary field that addresses scientific and clinical questions in vaccinology using computational and informatics approaches. Computational vaccinology overlaps with many other fields such as immunoinformatics, reverse vaccinology, postlicensure vaccine research, vaccinomics, literature mining, and systems vaccinology. The second ISV Pre-conference Computational Vaccinology Workshop (ICoVax 2012) was held on October 13, 2013 in Shanghai, China. A number of topics were presented in the workshop, including allergen predictions, prediction of linear T cell epitopes and functional conformational epitopes, prediction of protein-ligand binding regions, vaccine design using reverse vaccinology, and case studies in computational vaccinology. Although a significant progress has been made to date, a number of challenges still exist in the field. This Editorial provides a list of major challenges for the future of computational vaccinology and identifies developing themes that will expand and evolve over the next few years.

Molecular docking analysis of 2009-H1N1 and 2004-H5N1 influenza virus HLA-B*4405-restricted HA epitope candidates: implications for TCR cross-recognition and vaccine development.

BACKGROUND: The pandemic 2009-H1N1 influenza virus circulated in the human population and caused thousands deaths worldwide. Studies on pandemic influenza vaccines have shown that T cell recognition to conserved epitopes and cross-reactive T cell responses are important when new strains emerge, especially in the absence of antibody cross-reactivity. In this work, using HLA-B*4405 and DM1-TCR structure model, we systematically generated high confidence conserved 2009-H1N1 T cell epitope candidates and investigated their potential cross-reactivity against H5N1 avian flu virus. RESULTS: Molecular docking analysis of differential DM1-TCR recognition of the 2009-H1N1 epitope candidates yielded a mosaic epitope (KEKMNTEFW) and potential H5N1 HA cross-reactive epitopes that could be applied as multivalent peptide towards influenza A vaccine development. Structural models of TCR cross-recognition between 2009-H1N1 and 2004-H5N1 revealed steric and topological effects of TCR contact residue mutations on TCR binding affinity. CONCLUSIONS: The results are novel with regard to HA epitopes and useful for developing possible vaccination strategies against the rapidly changing influenza viruses. Yet, the challenge of identifying epitope candidates that result in heterologous T cell immunity under natural influenza infection conditions can only be overcome if more structural data on the TCR repertoire become available.