Paul P. Gardner

Paul P. Gardner
University of Otago · Department of Biochemistry

PhD

About

189
Publications
28,659
Reads
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6,974
Citations
Additional affiliations
January 2018 - present
University of Otago
Position
  • Professor (Associate)
June 2011 - January 2018
University of Canterbury
Position
  • Professor (Associate)
July 2007 - April 2011
Wellcome Sanger Institute
Position
  • Senior Researcher
Education
April 2000 - April 2003
Massey University
Field of study
  • Biomathematics
February 1996 - November 2000
Massey University
Field of study
  • Mathematics

Publications

Publications (189)
Preprint
Motivation Almost all cellular processes require protein-protein interactions. Common interaction types include binding, post-translational modifications, and catalysis. However, existing prediction tools do not take these interaction types into account and do not scale well on proteome-wide prediction. Results Here we show that a random forest cl...
Article
Full-text available
Background Computational biology provides software tools for testing and making inferences about biological data. In the face of increasing volumes of data, heuristic methods that trade software speed for accuracy may be employed. We have studied these trade-offs using the results of a large number of independent software benchmarks, and evaluated...
Article
Full-text available
Most research articles presenting new data analysis methods claim that “the new method performs better than existing methods,” but the veracity of such statements is questionable. Our manuscript discusses and illustrates consequences of the optimistic bias occurring during the evaluation of novel data analysis methods, that is, all biases resulting...
Article
Full-text available
Recombinant protein production is a key process in generating proteins of interest in the pharmaceutical industry and biomedical research. However, about 50% of recombinant proteins fail to be expressed in a variety of host cells. Here we show that the accessibility of translation initiation sites modelled using the mRNA base-unpairing across the B...
Article
We recently developed a high-throughput functional genomics approach, named ‘SorTn-seq’, to identify factors affecting expression of any gene of interest in bacteria. Our approach facilitates high-throughput screening of complex mutant pools, a task previously hindered by a lack of suitable techniques. SorTn-seq combines high-density, Tn5-like tran...
Article
Some Serratia entomophila isolates have been successfully exploited in biopesticides due to their ability to cause amber disease in larvae of the Aotearoa (New Zealand) endemic pasture pest, Costelytra giveni. Anti‐feeding prophage and ABC toxin complex virulence determinants are encoded by a 153‐kb single‐copy conjugative plasmid (pADAP; amber dis...
Article
Full-text available
Experiments that are planned using accurate prediction algorithms will mitigate failures in recombinant protein production. We have developed TISIGNER (https://tisigner.com) with the aim of addressing technical challenges to recombinant protein production. We offer three web services, TIsigner (Translation Initiation coding region designer), SoDoPE...
Article
Full-text available
Bacteria harbour multiple innate defences and adaptive CRISPR–Cas systems that provide immunity against bacteriophages and mobile genetic elements. Although some bacteria modulate defences in response to population density, stress and metabolic state, a lack of high-throughput methods to systematically reveal regulators has hampered efforts to unde...
Preprint
Most research articles presenting new data analysis methods claim that “the new method performs better than existing methods”, but the veracity of such statements is questionable. Our manuscript discusses and illustrates consequences of the optimistic bias occurring during the evaluation of novel data analysis methods, that is, all biases resulting...
Preprint
Full-text available
Motivation Signal peptides are responsible for protein transport and secretion and are ubiquitous to all forms of life. The annotation of signal peptides is important for understanding protein translocation and toxin secretion, optimising recombinant protein expression, as well as for disease diagnosis and metagenomics. Results Here we explore the...
Article
Full-text available
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Article
Full-text available
The tuatara (Sphenodon punctatus)—the only living member of the reptilian order Rhynchocephalia (Sphenodontia), once widespread across Gondwana1,2—is an iconic species that is endemic to New Zealand2,3. A key link to the now-extinct stem reptiles (from which dinosaurs, modern reptiles, birds and mammals evolved), the tuatara provides key insights i...
Preprint
Full-text available
Planning experiments using accurate prediction algorithms could mitigate failures in recombinant protein production. We have developed TISIGNER.com with the aim of addressing the technical challenges in recombinant protein production. We offer two web services, TIsigner (Translation Initiation coding region designer) and SoDoPE (Soluble Domain for...
Article
Full-text available
Motivation: Recombinant protein production is a widely used technique in the biotechnology and biomedical industries, yet only a quarter of target proteins are soluble and can therefore be purified. Results: We have discovered that global structural flexibility, which can be modeled by normalised B-factors, accurately predicts the solubility of...
Article
Full-text available
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Article
Full-text available
Background The giant squid (Architeuthis dux; Steenstrup, 1857) is an enigmatic giant mollusc with a circumglobal distribution in the deep ocean, except in the high Arctic and Antarctic waters. The elusiveness of the species makes it difficult to study. Thus, having a genome assembled for this deep-sea–dwelling species will allow several pending ev...
Article
Full-text available
CRISPR–Cas systems provide bacteria with adaptive immunity against bacteriophages1. However, DNA modification2,3, the production of anti-CRISPR proteins4,5 and potentially other strategies enable phages to evade CRISPR–Cas. Here, we discovered a Serratia jumbo phage that evades type I CRISPR–Cas systems, but is sensitive to type III immunity. Jumbo...
Preprint
Full-text available
The tuatara (Sphenodon punctatus), the only living member of the archaic reptilian order Rhynchocephalia (Sphenodontia) once widespread across Gondwana, is an iconic and enigmatic terrestrial vertebrate endemic to New Zealand. A key link to the now extinct stem reptiles from which dinosaurs, modern reptiles, birds and mammals evolved, the tuatara p...
Preprint
Full-text available
CRISPR-Cas systems provide bacteria with adaptive immunity against bacteriophages. However, DNA modification, the production of anti-CRISPR proteins and potentially other strategies enable phages to evade CRISPR-Cas. Here we discovered a Serratia jumbophage that evaded type I CRISPR-Cas systems, but was sensitive to type III immunity. Jumbophage in...
Preprint
Full-text available
Recombinant protein production in microbial systems is well-established, yet half of these experiments have failed in the expression phase. Failures are expected for 'difficult-to-express' proteins, but for others, codon bias, mRNA folding, avoidance, and G+C content have been suggested to explain observed levels of protein expression. However, det...
Article
Full-text available
In computational biology and other sciences, researchers are frequently faced with a choice between several computational methods for performing data analyses. Benchmarking studies aim to rigorously compare the performance of different methods using well-characterized benchmark datasets, to determine the strengths of each method or to provide recom...
Article
Full-text available
A core question in evolutionary biology is whether convergent phenotypic evolution is driven by convergent molecular changes in proteins or regulatory regions. We combined phylogenomic, developmental, and epigenomic analysis of 11 new genomes of paleognathous birds, including an extinct moa, to show that convergent evolution of regulatory regions,...
Article
Understanding how new genes originate and integrate into cellular networks is key to understanding evolution. Bacteria present unique opportunities for both the natural history and experimental study of gene origins, due to their large effective population sizes, rapid generation times, and ease of genetic manipulation. Bacterial small non-coding R...
Article
Full-text available
Campylobacter jejuni is the most common cause of bacterial diarrheal disease in the world. Clinical outcomes of infection can range from asymptomatic infection to life-threatening extraintestinal infections. This variability in outcomes for infected patients has raised questions as to whether genetic differences between C. jejuni isolates contribut...
Article
Full-text available
Metagenomic and meta-barcode DNA sequencing has rapidly become a widely-used technique for investigating a range of questions, particularly related to health and environmental monitoring. There has also been a proliferation of bioinformatic tools for analysing metagenomic and amplicon datasets, which makes selecting adequate tools a significant cha...
Preprint
Full-text available
The reactions of functional molecules like proteins and RNAs to mutation affect both host cell viability and biomolecular evolution. These molecules are considered robust if function is maintained despite mutations. Proteins and RNAs have different structural and functional characteristics that affect their robustness, and to date, comparisons betw...
Preprint
Full-text available
Environmental DNA sequencing has rapidly become a widely-used technique for investigating a range of questions, particularly related to health and environmental monitoring. There has also been a proliferation of bioinformatic tools for analysing metagenomic and amplicon datasets, which makes selecting adequate tools a significant challenge. A numbe...
Article
Full-text available
Emerging pathogens are a major threat to public health, however understanding how pathogens adapt to new niches remains a challenge. New methods are urgently required to provide functional insights into pathogens from the massive genomic data sets now being generated from routine pathogen surveillance for epidemiological purposes. Here, we measure...
Data
Invasiveness index assigned to validation strains of Salmonella. (TIF)
Data
Phylogeny of the Salmonella serovars used in this study. The tree was constructed in RAxML using a core gene alignment produced by Roary. Invasive serovars are highlighted in red. (TIF)
Data
Genes in S. Typhimurium ST313 above (intact, purple) or below (attenuated, green) bitscore threshold defined by random forest model for detecting gene degradation associated with invasive isolates. Genes for which homology to the reference sequence was not detected (usually due to extreme truncation) are marked in orange. (TIF)
Data
Additional details on training and testing of the random forest model. (PDF)
Data
Bitscore values from the genes from the genes fimD and fimH combined are better predictors of phenotype than either gene individually. (TIF)
Data
Invasiveness scores for S. Typhimurium ST313 isolates. A: RAxML tree of all ST313 isolates included in the study, annotated with invasiveness ranking and lineage. B: Invasiveness index for all ST313 isolates. C: Proportion of isolates carrying HACs in ST313 compared to other sequence types. (TIF)
Data
Accession numbers of Salmonella enterica serovars used in this study. (XLSX)
Data
Counts of high-impact (DBS in the top quartile) independent mutations in each top predictor gene for each strain. (XLSX)
Data
Metadata and invasiveness indices for S. Enteritidis iNTS strains. (XLSX)
Data
Top predictor genes. (XLSX)
Data
Metadata and invasiveness indices for S. Typhimurium iNTS strains. (XLSX)
Article
Full-text available
DNA based techniques are increasingly used for measuring the biodiversity (species presence, identity, abundance and community composition) of terrestrial and aquatic ecosystems. While there are numerous reviews of molecular methods and bioinformatic steps, there has been little consideration of the methods used to collect samples upon which these...
Article
Full-text available
Mammalian diversification has coincided with a rapid proliferation of various types of non-coding RNAs, including members of both snRNAs and snoRNAs. The significance of this expansion however remains obscure. While some ncRNA copy-number expansions have been linked to functionally tractable effects, such events may equally likely be neutral, perha...
Preprint
Full-text available
Emerging pathogens are a major threat to public health, however understanding how pathogens adapt to new niches remains a challenge. New methods are urgently required to provide functional insights into pathogens from the massive genomic data sets now being generated from routine pathogen surveillance for epidemiological purposes. Here, we measure...
Preprint
Full-text available
The relative roles of regulatory and protein evolution in the origin and loss of convergent phenotypic traits is a core question in evolutionary biology. Here we combine phylogenomic, epigenomic and developmental data to show that convergent evolution of regulatory regions, but not protein-coding genes, is associated with flightlessness in palaeogn...
Article
Full-text available
Neisseria meningitidis causes meningococcal disease but is frequently carried in the throats of healthy individuals; the factors that determine whether invasive disease develops are not completely understood. We carried out detailed studies of isolates, collected from patients and their household contacts, to identify differences between commensal...
Article
Full-text available
Background The New Zealand collembolan genus Holacanthella contains the largest species of springtails (Collembola) in the world. Using Illumina technology we have sequenced and assembled a draft genome and transcriptome from Holacanthella duospinosa (Salmon). We have used this annotated assembly to investigate the genetic basis of a range of trait...
Article
Full-text available
Legionella is a highly diverse genus of intracellular bacterial pathogens that cause Legionnaire’s disease (LD), an often severe form of pneumonia. Two L. micdadei sp. clinical isolates, obtained from patients hospitalized with LD from geographically distinct areas, were sequenced using PacBio SMRT cell technology, identifying incomplete phage regi...
Article
Full-text available
Pseudomonas syringae pv. actinidiae (Psa), the causal agent of kiwifruit canker, is one of the most devastating plant diseases of recent times. We have generated two mini-Tn5-based random insertion libraries of Psa ICMP 18884. The first, a ‘phenotype of interest’ (POI) library, consists of 10,368 independent mutants gridded into 96-well plates. By...
Data
Distribution of transposon insertion sites across the Psa chromosome and plasmid. The scatter plots show the insertion index, computed for each protein-coding gene as a function of position on the Psa chromosome (left) and plasmid (right). In brief, the insertion index for each gene is computed using the count of unique transposon insertion sites i...
Data
Vector map of pKRCPN2. pKRCPN2 harbors the mini-Tn5-based transposon Tn-DS1028uidAKm, which itself carries a uidA (β-glucuronidase; GUS) reporter gene and kanamycin resistance cassette (kan2) for the tracking and selection of Psa transposon mutants, respectively. pKRCPN2 also carries a tetracycline resistance gene (TcR) and an R6Kγ origin of replic...
Data
List of Psa transposon mutants identified in this study. (DOCX)
Data
Flow diagram detailing generation of the Psa mutant of interest (MOI) and phenotype of interest (POI) libraries. The final concentration of kanamycin (Km) used in King’s B (KB) agar and liquid media was 50 μg/mL. (TIF)
Data
Example of transposon insertion sites across the Psa chromosome. (A) a region of the Psa genome adjacent to the origin of replication; (B) a region from the conserved effector locus of the Psa genome. Transposon insertion sites are denoted by grey vertical lines, predicted coding regions as yellow bars and HrpL boxes by light blue triangles. The im...
Data
Transposon insertion settings and statistics. (DOCX)
Article
Full-text available
Toxin-antitoxin (TA) systems are gene modules that appear to be horizontally mobile across a wide range of prokaryotes. It has been proposed that type I TA systems, with an antisense RNA-antitoxin, are less mobile than other TAs that rely on direct toxin-antitoxin binding but no direct comparisons have been made. We searched for type I, II and III...
Preprint
Full-text available
Computational biology has provided widely used and powerful software tools for testing and making inferences about biological data. In the face of increasing volumes of data, heuristic methods that trade software speed for mathematical completeness must be employed. We are interested in whether trade-offs between speed and accuracy are reasonable....
Article
Full-text available
Motivation: The aim of this study is to assess the performance of RNA-RNA interaction prediction tools for all domains of life. Results: Minimum free energy (MFE) and alignment methods constitute most of the current RNA interaction prediction algorithms. The MFE tools that include accessibility (i.e. RNAup, IntaRNA and RNAplex) to the final pred...
Data