Injection site vaccinology of a recombinant vaccinia-based vector reveals diverse innate immune signatures

Poxvirus systems have been extensively used as vaccine vectors. Herein a RNA-Seq analysis of intramuscular injection sites provided detailed insights into host innate immune responses, as well as expression of vector and recombinant immunogen genes, after vaccination with a new multiplication defective, vaccinia-based vector, Sementis Copenhagen Vector. Chikungunya and Zika virus immunogen mRNA and protein expression was associated with necrosing skeletal muscle cells surrounded by mixed cellular infiltrates. The multiple adjuvant signatures at 12 hours post-vaccination were dominated by TLR3, 4 and 9, STING, MAVS, PKR and the inflammasome. Th1 cytokine signatures were dominated by IFNγ, TNF and IL1β, and chemokine signatures by CCL5 and CXCL12. Multiple signatures associated with dendritic cell stimulation were evident. By day seven, vaccine transcripts were absent, and cell death, neutrophil, macrophage and inflammation annotations had abated. No compelling arthritis signatures were identified. Such injection site vaccinology approaches should inform refinements in poxvirus-based vector design.Jessamine E. Hazlewood, Troy Dumenil, Thuy T. Le, Andrii Slonchak, Stephen H. Kazakoff, Ann-Marie Patch ... et al

Genetic and genomic analysis of the tree legume Pongamia pinnata as a feedstock for biofuels

The tree legume Pongamia {Pongamia pinnata (L.) Pierre [syn. Millettia pinnata (L.) Panigrahi]} is emerging as an important biofuels feedstock. It produces about 30 kg per tree per year of seeds, containing up to 55% oil (w/v), of which approximately 50% is oleic acid (C18:1). The capacity for biological N fixation places Pongamia in a more sustainable position than current nonlegume biofuel feedstocks. Also due to its drought and salinity tolerance, Pongamia can grow on marginal land not destined for production of food. As part of the effort to domesticate Pongamia our research group at The University of Queensland has started to develop specific genetic and genomic tools. Much of the preliminary work to date has focused on characterizing the genetic diversity of wild populations. This diversity is reflective of the outcrossing reproductive biology of Pongamia and necessitates the requirement to develop clonal propagation protocols. Both the chloroplast and mitochondrial genomes of Pongamia have been sequenced and annotated (152,968 and 425,718 bp, respectively), with similarities to previously characterized legume organelle genomes. Many nuclear genes associated with oil biosynthesis and nodulation in Pongamia have been characterized. The continued application of genetic and genomic tools will support the deployment of Pongamia as a sustainable biofuel feedstock

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation; analyses timings and patterns of tumour evolution; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity; and evaluates a range of more-specialized features of cancer genomes