Three of our undergraduate students gave poster presentations in the last month. Arjun Sharma (Biochemistry & Biomedical Sciences 3rd year) outlined his work on developing the Comprehensive Antibiotic Resistance Database’s (arpcard.mcmaster.ca) CARD*Shark text mining algorithms at the Michael G. DeGroote Institute for Infectious Disease Research (IIDR) Trainee Day while Kirill Pankov (Biomedical Discovery & Commercialization 4th year) presented the results of his summer NSERC Undergraduate Student Research Award (USRA) research in the Laboratory of Dr. Joanna Wilson into the origin of Cnidarian P450 enzymes, work he is continuing in our lab as part of his thesis research. Mohammad Khan (Biomedical Discovery & Commercialization 4th year), a thesis student in the Laboratory of Dr. Eric Brown that collaborates with our group, also presented a poster at IIDR Trainee Day on his work on chemical-genetic interaction database design.
Sharma, A.N., S. Doshi, A.R. Raphenya, B. Alcock, B.M. Dave, B.A. Lago, K.K. Tsang, & A.G. McArthur. 2016. CARDShark: Computer-assisted biocuration of the Comprehensive Antibiotic Resistance Database. Poster presentation at the 2016 Michael G. DeGroote Institute for Infectious Disease Research (IIDR) Trainee Day, Hamilton, Ontario, Canada.
Pankov, K., A.G. McArthur & J.Y. Wilson. 2016. The Cytochrome P450 (CYP) superfamily in the Cnidarian phylum. Poster presentation at the 2016 Undergraduate Student Research Awards (USRA) Poster Session, Hamilton, Ontario, Canada.
Khan, M.A., S. French, B. Aubie, A.G McArthur & E.D. Brown. 2016. Challenging common screening filters through analysis of a chemical-genetic screening database. Poster presentation at the 2016 Michael G. DeGroote Institute for Infectious Disease Research (IIDR) Trainee Day, Hamilton, Ontario, Canada.
YphC and YsxC are GTPases in Bacillus subtilis that facilitate the assembly of the 50S ribosomal subunit, however their roles in this process are still uncharacterized. To explore their function, we used strains in which the only copy of the yphC or ysxC genes were under the control of an inducible promoter. Under depletion conditions, they accumulated incomplete ribosomal subunits that we named 45SYphC and 44.5SYsxC particles. Quantitative mass spectrometry analysis and the 5-6 Å resolution cryo-EM maps of the 45SYphC and 44.5SYsxC particles revealed that the two GTPases participate in the maturation of the central protuberance, GTPase associated region and key RNA helices in the A, P and E functional sites of the 50S subunit. We observed that YphC and YsxC bind specifically to the two immature particles, suggesting that they represent either on-pathway intermediates or that their structure has not significantly diverged from that of the actual substrate. These results describe the nature of these immature particles, a widely used tool to study the assembly process of the ribosome. They also provide the first insights into the function of YphC and YsxC in 50S subunit assembly and are consistent with this process occurring through multiple parallel pathways, as it has been described for the 30S subunit.
A cross-national research consortia co-led by McMaster’s Andrew McArthur is receiving two of 16 federal grants to further develop a big data solution to the growing problem of antimicrobial resistance (AMR). The government’s investment, totaling more than $4M, is the result of Genome Canada’s 2015 Bioinformatics and Computational Biology Competition, a partnership with the Canadian Institutes of Health Research (CIHR). McArthur and his colleagues will receive $500,000 over two years. McArthur will work closely with researchers from the University of British Columbia, Simon Fraser University, Dalhousie University and the Public Health Agency of Canada to design and develop novel software and database systems that will empower public health agencies and the agri-food sector to rapidly respond to threats posed by infectious disease outbreaks and food-borne illnesses.
Kara Tsang (graduate, McMaster BDC) – Kara did her BiomedDC 4A15 thesis in the lab, focused on Pseudomonas resistome prediction and cystic fibrosis-associated metagenomic sequencing and starts September 2016 as MSc student in the area of clinical AMR analytics, particularly metagenomics. Her work will be part of our recently funded Genome Canada grants, as well as part of McMaster’s clinical genome sequencing efforts.
Krishna Srinivasan (graduate, McMaster Biology) – Krishna just finished his undergraduate degree in McMaster’s Biology department, with a thesis in environmental toxicology. He starts as a MSc student September 2016, collaborating with the Jenny lab (UAlabama) on our recently funded NIH grant examining the role of MTF-1 in lens development and cataractogenesis.
McArthur, A.G., B. Jia, A.R. Raphenya, P. Guo, K. Tsang, B. Dave, B. Alcock, B. Lago, N. Waglechner, & G.D. Wright. 2016. The Comprehensive Antibiotic Resistance Database – A Platform for Antimicrobial Resistance Surveillance. Invited presentation at the 2nd Conference Rapid Microbial NGS and Bioinformatics: Translation Into Practice, Hamburg, Germany.
Antimicrobial resistance (AMR) is among the most pressing public health crises of the 21st Century. Despite the importance of resistance to health, this field has been slow to take advantage of genome scale tools. Phenotype based criteria dominate the epidemiology of antibiotic action and effectiveness. There is a poor understanding of which antibiotic resistance genes are in circulation, which a threat, and how clinicians and public health workers can manage the crisis of resistance. However, DNA sequencing is rapidly decreasing in cost and as such we are on the cusp of an age of high-throughput molecular epidemiology. What are needed are tools for rapid, accurate analysis of DNA sequence data for the genetic underpinnings of antibiotic resistance. In an effort to address this problem, we have created the Comprehensive Antibiotic Resistance Database (card.mcmaster.ca). This database is a rigorously curated collection of known antibiotics, targets, and resistance determinants. It integrates disparate molecular and sequence data, provides a unique organizing principle in the form of the Antibiotic Resistance Ontology (ARO), and can quickly identify putative antibiotic resistance genes in raw genome sequences using the novel Resistance Gene Identifier (RGI). Here we review the current state of the CARD, particularly recent advances in the curation of resistance determinants and the structure of the ARO. We will also present our plans for development of semi- and fully-automated text mining algorithms for curation of broader AMR data, construction of meta-models for improved AMR phenotype prediction, and release of portable command-line genome analysis tools.
* presenter underlined, trainees in bold
Congratulations to Kara Tsang and Zachary Lin on completion of their Biomedical Discovery and Commercialization (BDC) 4A15 thesis research! Both Kara & Zachary presented their research results at the 2016 BDC Engage Symposium.
Zachary Lin: Adapting Galaxy bioinformatics to outbreak- associated Clostridium difficile
Kara Tsang: The translation of biocuration to metagenomic analysis for combatting multi-drug resistant Pseudomonas aeruginosa
Combatting Antibiotic Resistance Using Surveillance – click on the image to watch the 10 minute video. More details here.
The completion of the human genome project in 2001 sparked the beginning of a sequencing revolution with applications that are only now being realized by researchers. The decreasing cost of DNA sequencing has ignited a continuous generation of genomic data with a limited number of researchers able to manipulate the output. Consequentially the demand to examine this genetic information has forced bioinformaticians to improve the analytical tools involved in sequence analysis. Galaxy is a user-friendly analytical platform where researchers without a computational background can navigate their way through an investigation and use various analytical tools and workflows to assist them with their genomic research (1). Galaxy enables the addition of novel software into the environment by individual users to fill in the gaps of tools that haven’t been created by the Galaxy team. This project will focus on a particular analytical gap concerning tools related to antibiotic resistance, phylogenetics, and bacterial virulence. Currently, the proposed software to be adapted to the galaxy setting includes a resistance gene identifier (RGI) associated with the comprehensive antibiotic resistance database (CARD) (2), a single nucleotide polymorphism identifier (BANSP) , and novel virulence factor identification software associated with the virulence factor database (VFDB) (3). The combination of Galaxy’s existing ToolShed and these unique additions will create a comprehensive analytical environment that can be applied to realistic situations. One such situation that this project will concentrate on refers specifically to the outbreaks of Clostridium difficile (C. diff) in the health care system.
The loss of effective antimicrobials is reducing the ability to protect the global population from infectious diseases, leading to profound impacts on the healthcare system, international trade, agriculture, and environment. The field of antibiotic drug discovery and the monitoring of the dynamic and new antibiotic resistance elements have yet to fully exploit the power of the genome revolution. The curation and directed development of the Comprehensive Antibiotic Database (CARD) will advance the understanding of the genetics, genomics, and threat severity of antibiotic resistance, while simultaneously improving its ability to accurately predict and screen for antibiotic resistance genes within raw genomes. Strategically advancing the Antibiotic Resistance Ontology (ARO), the unique organizing principle of the CARD, allows the value of big data in disparate realms of research to be used and understood by the multidisciplinary efforts working to combat the emergence and prevalence of the ESKAPE pathogens, a critical driving force of the global health crisis.