Tuesday, 15 August 2017

High risk human papilloma viruses (HPVs) are present in benign prostate tissues before development of HPV associated prostate cancer

Glenn WK, Ngan CC, Amos TG, Edwards RJ, Swift J, Lutze-Mann L, Shang F, Whitaker NJ & Lawson JS (2017): High risk human papilloma viruses (HPVs) are present in benign prostate tissues before development of HPV associated prostate cancer. Infectious Agents and Cancer 12:46.

Abstract

Background. Although high risk HPVs are associated with an increased risk of prostate cancer it is not known if they have a causal role. The purpose of this study is to investigate the potential role of human papilloma viruses (HPVs) in prostate cancer. The aims are (i) to investigate the presence and confirm the identity of high risk HPVs in benign prostate tissues prior to the development of HPV positive prostate cancer in the same patients, and (ii) to determine if HPVs are biologically active.

Methods. We used polymerase chain reaction (PCR) to identify HPVs in specimens from 52 Australian men with benign prostate biopsies who 1 to 10 years later developed prostate cancer. Immunohistochemistry (IHC) was used to assess the expression of HPV E7 oncoproteins, cytokeratin and prostate specific antigen (PSA).

We used RNASeq data from The Cancer Genome Atlas (TCGA) to identify possible HPV RNA sequences in prostate cancer.

Results. HPV screening using standard PCR was conducted on 28 of the 52 sets of benign and later prostate cancers. HPV L1 genes were identified in 13 (46%) benign and 8 (29%) of 28 later prostate cancers in the same patients. HPV E7 genes were identified in 23 (82%) benign and 19 (68%) of 28 subsequent prostate cancers in the same patients. The same HPV types were present in both the benign and subsequent prostate cancers in 9 sets of specimens. HPV type 16 was identified in 15% of benign and 3% of prostate cancers. HPV type 18 was identified in 26% of benign and 16% of prostate cancers. Small numbers of HPV types 45, 47, 76 and 115 were also identified.

High confidence RNA-Seq evidence for high risk HPV types 16 and 18 was identified in 12 (2%) of the 502 TCGA prostate cancer transcriptomes.

High risk HPV E7 oncoprotein was positively expressed in 23 (82%) of 28 benign prostate specimens but only in 8 (29%) of 28 of the later prostate cancer specimens. This difference is statistically significant (p = 0.001). Prostate specific antigen (PSA) was more highly expressed in 26 (50%) of 52 prostate cancer specimens as compared to prior benign prostate specimens in the same patients.

Conclusions. High risk HPVs are present in benign prostate tissues prior to the development of HPV positive prostate cancer. There is a significantly higher expression of HPV E7 oncoproteins in benign prostate tissues as compared to late prostate cancer that subsequently developed in the same patients. This observation suggests that HPV oncogenic activity is an early phenomenon in a majority of prostate oncogenesis. TCGA RNA-Seq data suggests that HPV is biologically active in some prostate tumour samples.

Emeritus Professor Jim Lawson has this to say about the study:

“Human papilloma viruses are the cause of cervical cancer in women. These viruses are sexually transmitted. Infections by human papilloma viruses can be prevented by effective vaccines including the Australian developed Gardosil.

Scientists from the University of New South Wales, Sydney, Australia, have identified high risk human papilloma viruses in normal prostate tissues 2 to 12 years before the development of human papilloma virus positive prostate cancer. While the scientists do not claim this is evidence that human papilloma viruses are a direct cause of prostate cancer, they advise that it is prudent for both men and women to act with caution.

Human papilloma viruses are present in semen in over 15% of men and can be readily transmitted during sexual activities.

Vaccines such as the Australian developed Gardosil, are safe and effective in preventing infections by human papilloma viruses. The University of New South Wales scientists strongly encourage both young men and women to prevent human papilloma virus infections by vaccination at a young age.”

Tuesday, 11 July 2017

The SLiMEnrich Shiny App is now live

SLiMEnrich

Sobia’s first Shiny App is now up and running for final pre-publication testing on our new EdwardsLab RShiny server. Please feel free to try it out. Any comments and suggestions can be posted here, by email, or via the GitHub issues page.

The SLiMEnrich App allows users to predict Domain-Motif Interactions (DMIs) from Protein-Protein Interaction data (PPI) and to estimate the background distribution of expected DMI by chance through a randomisation approach. The walkthrough has more details.

SLiMEnrich can be used to:

  • Estimate the enrichment of SLiM-mediated DMI in a given PPI dataset.
  • Generate predictions for DMI-mediated from a PPI dataset. Predictions are based on known SLiM-Domain interactions.
  • Estimate the False Positive Rate of those DMI predictions.
  • With a bit of imagination, SLiMEnrich can be adapted to generate and assess predictions for other kinds of interactions. See docs for details.

    SLiMEnrich is available via the SLiMEnrich RShiny webserver and can be downloaded for local running from the SLiMEnrich GitHub repo.

    Tuesday, 4 July 2017

    GEN2017: Mitochondrial variation and heteroplasmy in Australian and Hawai’ian cane toads

    If you were attending this year’s Annual Conference of the Genetics Society of Australasia with the NZ Society for Biochemistry & Molecular Biology, hopefully you made it to the oral presentation of Lee Ann Rollins. Although we do not yet have enough PacBio data for a pure long read assembly of the nuclear genome, the mitochondrion is another matter!

    Mitochondrial variation and heteroplasmy in Australian and Hawai’ian cane toads.

    Lee A Rollins[1], Mark F Richardson[1], Daniel M Selechnik[2], Andrea J West[1], Timothy G Amos[3], Richard J Edwards[3] & Richard Shine[2]

    1. School of Life and Environmental Sciences, Centre for Integrative Ecology, Deakin University, Geelong, VIC, Australia
    2. School of Life and Environmental Sciences, University of Sydney, Sydney, NSW, Australia
    3. School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW, Australia

    Abstract

    Background/Aims. Invasive species can adapt to new environments despite low levels of standing genetic diversity due to small founding numbers or sequential introductions. The iconic Australian cane toad was sourced from an introduced population in Hawai’i and conflicting evidence exists regarding the level of genetic diversity across these invasions.

    Methods. We extracted mitochondrial sequence data from the genome of one individual sequenced using the PacBio RSII and Illumina X10 platforms. From these data, we assembled and annotated the mitochondrial genome. RNAseq data from 18 individuals collected from Hawai’i and 68 individuals from Australia were aligned to the reference sequence. We quantified polymorphism across samples and heteroplasmy (multiple mitochondrial haplotypes within individuals).

    Results. A complete, annotated mitochondrial reference genome was constructed consisting of 18154 base pairs (bp), the largest reported bufonid mitochondrial genome. We aligned RNAseq data to the entire reference sequence, with the exception of a 347bp region containing several 104bp repeats. We identified 16 polymorphisms (17 haplotypes); one haplotype was common to 65 individuals sampled in both introductions. Heteroplasmy was detected at most polymorphic sites and also at multiple sites where the predominant haplotype was common to all individuals.

    Conclusions. Mitochondrial diversity is low in Australian and Hawai’ian cane toads. Our findings add to the growing body of evidence that heteroplasmy may be ubiquitous across taxa. Selection within heteroplasmic individuals (recently demonstrated in expanding populations) may provide an important source of variation in genetically depauperate populations.

    Funding. Australian Research Council DE150101393 (LAR) and FL120100074 (RS)

    Friday, 30 June 2017

    Research Snapshot - June 2017

    Research interests in the Edwards lab stem from a fascination with the molecular basis of evolutionary change and how we can harness the genetic sequence patterns left behind to make useful predictions about contemporary biological systems. We are a bioinformatics lab but like to incorporate bench data through collaboration wherever possible.

    Main Research

    The core research in the lab is broadly divided into three main themes:

    1. Short Linear Motifs (SLiMs)

    SLiMs are short regions of proteins that mediate interactions with other proteins. A major focus of the lab is the computational prediction of SLiMs from protein sequences. This research originated with Rich’s postdoctoral research, during which he developed a sequence analysis methods for the rational design of biologically active short peptides. He subsequently developed SLiMDisc, one of the first algorithms for successfully predicting novel SLiMs from sequence data - and coined the term “SLiM” into the bargain. This subsequently lead to the development of SLiMFinder, the first SLiM prediction algorithm able to estimate the statistical significance of motif predictions. SLiMFinder greatly increased the reliability of predictions. SLiMFinder has since spawned a number of motif discovery tools and webservers and is still arguably the most successful SLiM prediction tool on benchmarking data.

    Current research is looking to develop these SLiM prediction tools further and apply them to important biological questions. Of particular interest is the molecular mimicry employed by viruses to interact with host proteins and the role of SLiMs in other diseases, such as cancer. Other work is concerned with the evolutionary dynamics of SLiMs within protein interaction networks.

    2. The evolution of novel functions.

    Previous work in the lab has focused on the evolution of functional specificity following gene duplication. Since moving to UNSW, activities have shifted more towards the use of PacBio long read sequencing and other cutting-edge sequencing technologies, working closely with the Ramaciotti Centre for Genomics. We are collaborating with industrial and academic partners to de novo sequence, assemble, annotate and interrogate the genomes of a selection of microbes with interesting metabolic abilities. Most notably, we have an ARC Linkage Grant with Microbiogen Pty Ltd. to understand how a strain of Saccharomyces cerevisiae has evolved to efficiently use xylose as a sole carbon source: something vital for second generation biofuel production that wild yeast cannot do. This project combines detailed molecular characterisation of highly adapted yeast strains with “molecular palaeontology” to trace the evolutionary process and identify functionally significant loci under selection.

    3. Whole genome sequencing and assembly.

    Following our experiences with de novo whole genome assembly in yeast, the lab is getting involved in an increasing number of genome sequencing projects. The biggest of these is leading the bioinformatics and assembly effort in a consortium to sequence the cane toad genome. The lab is also leading the BABS Genome project to sequence iconic Australian species for use in teaching and public engagement.

    Previous Research

    The lab has been involved in a number of interdisciplinary collaborative projects applying bioinformatics tools and molecular evolution theory to experimental biology, often using large genomic, transcriptomic and/or proteomic datasets. These projects often involved the development of bespoke bioinformatics pipelines and a number of open source bioinformatics tools have been generated as a result. Please see the Publications and Lab software pages for more detail, or get in touch if something catches your eye and you want to find out more.

    Tuesday, 20 June 2017

    UNSW Genome Annotation Workshop cancelled

    Regrettably, due to unforeseen circumstances, EMBL-ABR’s Monica Munoz-Torres Australian tour has been cancelled. As a result, the planned UNSW Genome Annotation Workshop will no longer be going ahead. We hope to organise something similar in future, so will leave the registration page up for a bit longer to get a list of interested parties.

    Sunday, 21 May 2017

    The 2017 BABS Genome Competition is on

    BABS researchers are involved in sequencing the genomes of a number of iconic Australian species. These include the koala, the cane toad, and Sandy the Dingo (winner of the PacBio World’s Most Interesting Genome competition). Now, we’re asking: what next?

    This year, BABS has launched a new initiative: the BABS Genome Project. We will be using the latest sequencing technologies at the Ramaciotti Centre for Genomics to sequence a brand new genome of an Australian organism. Students and staff of BABS3291 Genes, Genomes and Evolution, will be the first scientists in the world to analyse the data.

    Australia has some of the most interesting - and deadly! - animals on earth. If you could sequence one, which would it be? Let us know at the BABS Genome survey. If you are a BABS student and give us the reason for your selection, you could win one of five $50 gift cards.

    Wednesday, 10 May 2017

    UNSW Genome Annotation Workshop

    NOTE: Regrettably, this event has now been cancelled. We hope to organise something similar in future and will be in touch with registered individuals to gauge interest.

    We are pleased to announce that we are hosting Monica Munoz-Torres from the Berkeley Bioinformatics Open-Source Projects group (BBOP) at Lawrence Berkeley National Laboratory as part of her EMBL-ABR Australian tour, sponsored by the School of Biotechnology and Biomolecular Sciences (BABS) and NSW Systems Biology Initiative (SBI).

    In addition to a BABS seminar (details to follow), Monica will be giving a one-day Primer on Genome Annotation workshop at UNSW, with a particular emphasis on collaborative genome annotation using WebApollo.

    • When: 0900-1700, July 7th, 2017
    • Where: Red Centre, UNSW, Sydney, Australia
    • Contact: richard.edwards@unsw.edu.au

    You can pre-register for the workshop here or fill in the form below. Places are limited to 30 participants. We will be in touch to let you know if you have a place. Formal registration will require a $20 registration fee.