Bernard de Bono | The University of Auckland (original) (raw)

Papers by Bernard de Bono

The Journal of Physiology, May 30, 2014

We outline an extension of phylogenetic studies of protein interaction networks to take into acco... more We outline an extension of phylogenetic studies of protein interaction networks to take into account biophysical constraints to interaction imposed by tissues regulating these networks and we define these constraints explicitly as a means to track the evolution of tissue structure and function objectively. r For biophysical constraints that are associated at the lowest spatial scales with molecular diffusion within and between cells that are less than 100 μm apart, we define a cylinder of 40 μm radius centred on a small vessel as the primary functional tissue unit (pFTU). r Molecular transport and communication between distributed or contiguous pFTUs via the endothelial or epithelial vessels is characterised at the level of secondary functional tissue units (sFTUs). sFTUs represent units of physiological function that are replicated multiple times in a whole organ. r Non-dimensional analysis, which expresses the relative importance of biophysical processes, provides the metrics to quantify and compare the function of FTUs for phylogenetic analysis. r We lay the ground for a systematic approach to the measurement of tissue structure and function, based on biophysical principles, at the level of primary and secondary FTUs.

Reactome, located at http://www.reactome.org is a curated, peer-reviewed resource of human biolog... more Reactome, located at http://www.reactome.org is a curated, peer-reviewed resource of human biological processes. Given the genetic makeup of an organism, the complete set of possible reactions constitutes its reactome. The basic unit of the Reactome database is a reaction; reactions are then grouped into causal chains to form pathways. The Reactome data model allows us to represent many diverse processes in the human system, including the pathways of intermediary metabolism, regulatory pathways, and signal transduction, and high-level processes, such as the cell cycle. Reactome provides a qualitative framework, on which quantitative data can be superimposed. Tools have been developed to facilitate custom data entry and annotation by expert biologists, and to allow visualization and exploration of the finished dataset as an interactive process map. Although our primary curational domain is pathways from Homo sapiens, we regularly create electronic projections of human pathways onto other organisms via putative orthologs, thus making Reactome relevant to model organism research communities. The database is publicly available under open source terms, which allows both its content and its software infrastructure to be freely used and redistributed.

Database, 2017

Neurodegenerative disorders such as Parkinson's and Alzheimer's disease are devastating and costl... more Neurodegenerative disorders such as Parkinson's and Alzheimer's disease are devastating and costly illnesses, a source of major global burden. In order to provide successful interventions for patients and reduce costs, both causes and pathological processes need to be understood. The ApiNATOMY project aims to contribute to our understanding of neurodegenerative disorders by manually curating and abstracting data from the vast body of literature amassed on these illnesses. As curation is labour-intensive, we aimed to speed up the process by automatically highlighting those parts of the PDF document of primary importance to the curator. Using techniques similar to those of summarisation, we developed an algorithm that relies on linguistic, semantic and spatial features. Employing this algorithm on a test set manually corrected for tool imprecision, we achieved a macro F 1-measure of 0.51, which is an increase of 132% compared to the best bag-of-words baseline model. A user based evaluation was also conducted to assess the usefulness of the methodology on 40 unseen publications, which reveals that in 85% of cases all highlighted sentences are relevant to the curation task and in about 65% of the cases, the highlights are sufficient to support the knowledge curation task without needing to consult the full text. In conclusion, we believe that these are promising results for a step in automating the recognition of curation-relevant sentences. Refining our approach to pre-digest papers will lead to faster processing and cost reduction in the curation process.

Interface Focus, Apr 6, 2016

One contribution of 12 to a theme issue 'The Human Physiome: a necessary key to the creative dest... more One contribution of 12 to a theme issue 'The Human Physiome: a necessary key to the creative destruction of medicine'.

Genomics, Apr 1, 2005

We have compiled an online database of known human defense genes: the Immunogenetic Related Infor... more We have compiled an online database of known human defense genes: the Immunogenetic Related Information Source (IRIS). As of October 1, 2004, there are 1562 immune genes recorded in IRIS, representing 7% of the human genome. This resource contains searchable information including chromosomal location, sequence data, and a curated functional annotation for each entry. We used IRIS as a basis for analyzing the composition and characteristics of the immune genome, such as gene clustering, polymorphism, and relationship to disease. High protein sequence similarity correlated inversely with distance between immune genes, consistent with clustering of duplicated loci. We also found that, even though some immune genes exhibit high levels of polymorphism, such as MHC class I, the range of levels of polymorphism in immune genes is similar to that of nonimmune genes. Approximately 20% of immune genes have a known disease association. IRIS

Reactome, Mar 11, 2008

The contents of this document may be freely copied and distributed in any media, provided the aut... more The contents of this document may be freely copied and distributed in any media, provided the authors, plus the institutions, are credited, as stated under the terms of Creative Commons Attribution 4.0 International (CC BY 4.0) License. For more information see our license.

Journal of Biomedical Semantics, 2013

Background: Histology information management relies on complex knowledge derived from morphologic... more Background: Histology information management relies on complex knowledge derived from morphological tissue analyses. These approaches have not significantly facilitated the general integration of tissue-and molecular-level knowledge across the board in support of a systematic classification of tissue function, as well as the coherent multi-scale study of physiology. Our work aims to support directly these integrative goals. Results: We describe, for the first time, the precise biophysical and topological characteristics of functional units of tissue. Such a unit consists of a three-dimensional block of cells centred around a capillary, such that each cell in this block is within diffusion distance from any other cell in the same block. We refer to this block as a functional tissue unit. As a means of simplifying the knowledge representation of this unit, and rendering this knowledge more amenable to automated reasoning and classification, we developed a simple descriptor of its cellular content and anatomical location, which we refer to as a primary tissue motif. In particular, a primary motif captures the set of cellular participants of diffusion-mediated interactions brokered by secreted products to create a tissue-level molecular network. Conclusions: Multi-organ communication, therefore, may be interpreted in terms of interactions between molecular networks housed by interconnected functional tissue units. By extension, a functional picture of an organ, or its tissue components, may be rationally assembled using a collection of these functional tissue units as building blocks. In our work, we outline the biophysical rationale for a rigorous definition of a unit of functional tissue organization, and demonstrate the application of primary motifs in tissue classification. In so doing, we acknowledge (i) the fundamental role of capillaries in directing and radically informing tissue architecture, as well as (ii) the importance of taking into full account the critical influence of neighbouring cellular environments when studying complex developmental and pathological phenomena.

European Journal of Immunology, Aug 1, 2008

Sialic acid binding immunoglobulin-like lectins (Siglec) are important components of immune recog... more Sialic acid binding immunoglobulin-like lectins (Siglec) are important components of immune recognition. The organization of Siglec genes in different species is consistent with rapid selection imposed by pathogens. We studied SIGLEC11 genes in human, rodent, dog, cow and non-human primates. The lineages of SIGLEC11 genes in these species have undergone dynamic gene duplication and conversion, forming a potential inhibitory (SIGLEC11)/activating (SIGLEC16) receptor pair in chimpanzee and humans. A cDNA encoding human Siglec-16, currently classed as a pseudogene in the databases (SIGLECP16), is expressed in various cell lines and tissues. A polymorphism screen for the two alleles (wild type and four-base pair deletion, 4bpDelta) of SIGLEC16 found their frequencies to be 50% amongst the UK population. A search for donor sequences for SIGLEC16 revealed a subfamily of activating Siglec with charged transmembrane domains predicted to associate with ITAM-encoding adaptor proteins. In support of this, Siglec-16 was expressed at the cell surface in the presence of DAP12, but not the FcRgamma chain. Using antisera specific to the cytoplasmic tail of Siglec-16, we identified Siglec-16 expression in CD14(+) tissue macrophages and in normal human brain, cancerous oesophagus and lung. This is the first activating human Siglec receptor found to have functional and non-functional alleles within the population.

Reactome, Sep 4, 2007

Immunogenetics, Apr 1, 2009

Seminars in Immunology, Aug 1, 2003

A better description of the immune system can be afforded if the latest developments in bioinform... more A better description of the immune system can be afforded if the latest developments in bioinformatics are applied to integrate sequence with structure and function. Clear guidelines for the upgrade of the bioinformatic capability of the immunogenetics laboratory are discussed in the light of more powerful methods to detect homology, combined approaches to predict the three dimensional properties of a protein and a robust strategy to represent the biological role of a gene.

Blood, Nov 16, 2008

In this study, we demonstrate the suitability of the vertebrate Danio rerio (zebrafish) for funct... more In this study, we demonstrate the suitability of the vertebrate Danio rerio (zebrafish) for functional screening of novel platelet genes in vivo by reverse genetics. Comparative transcript analysis of platelets and their precursor cell, the megakaryocyte, together with nucleated blood cell elements, endothelial cells, and erythroblasts, identified novel platelet membrane proteins with hitherto unknown roles in thrombus formation. We determined the phenotype induced by antisense morpholino oligonucleotide (MO)-based knockdown of 5 of these genes in a laser-induced arterial thrombosis model. To validate the model, the genes for platelet glycoprotein (GP) IIb and the coagulation protein factor VIII were targeted. MO-injected fish showed normal thrombus initiation but severely impaired thrombus growth, consistent with the mouse knockout phenotypes, and concomitant knockdown of both resulted in spontaneous bleeding. Knock-down of 4 of the 5 novel platelet proteins altered arterial thrombosis, as demonstrated by modified kinetics of thrombus initiation and/or development. We identified a putative role for BAMBI and LRRC32 in promotion and DCBLD2 and ESAM in inhibition of thrombus formation. We conclude that phenotypic analysis of MOinjected zebrafish is a fast and powerful method for initial screening of novel platelet proteins for function in thrombosis.

Trends in Biochemical Sciences, 2001