Detailed Molecular and Immune Marker Profiling of Archival Prostate Cancer Samples Reveals an Inverse Association between TMPRSS2:ERG Fusion Status and Immune Cell Infiltration

Prostate cancer is a significant global health issue and limitations to current patient management pathways often result in over- or under-treatment. New ways to stratify patients are urgently needed. We conducted a feasibility study of such novel assessments looking for associations between genomic changes and lymphocyte infiltration. An innovative workflow utilizing an in-house targeted sequencing panel, immune cell profiling using an image analysis pipeline, RNA-Seq, and exome sequencing in select cases was tested. Gene fusions were profiled by RNA-seq in 27/27 cases and a significantly higher TIL count was noted in tumors without a TMPRSS2:ERG fusion compared to those with the fusion (P = 0.01). Although this finding was not replicated in a larger validation set (n=436) of The Cancer Genome Atlas images, there was a trend in the same direction. Differential expression analysis of TIL-High and TIL-Low tumors revealed the enrichment of both innate and adaptive immune response pathways. Mutations in mismatch repair genes (MLH1 and MSH6 mutations in 1/27 cases) were identified. We describe a potential immune escape mechanism in TMPRSS2:ERG fusion positive tumors. Detailed profiling, as shown here, can provide novel insights into tumor biology. Likely differences with findings with other cohorts are related to methods used to define region of interest, but this warrants further study in a larger cohort

Visualizing Chimeric RNA

Chimeric RNA molecules, or fusion transcripts, are transcripts where exons from two or more different genes are fused into one transcript. These have the potential to encode novel proteins, and might play roles in the development of cancer. Advantages in high throughput RNA sequencing have made it easier to detect fusion transcripts, but the software used to detect fusions from sequencing data often yield a high false discovery rate. To evaluate which of the chimeric RNA molecules observed in cancer cells are relevant for the development of the disease, good prioritization of the results is important. This will be helped by a visualization framework that automatically integrates RNA data with known genomic features. In this thesis, we have developed an R package that automates the creation of chimeric RNA visualizations. The package, named chimeraviz, implements a unified format for representing fusion transcripts, and can take input from nine different fusion-finder tools. The package provides sorting and filtering functions, as well as multiple visualizations of chimeric RNA molecules that improves upon what has been seen in the literature previously

Strategy for Detection and High-Resolution Characterization of Authigenic Carbonate Cold Seep Habitats Using Ships and Autonomous Underwater Vehicles on Glacially Influenced Terrain

Cold seep habitats with authigenic carbonates and associated chemosynthetic communities in glacially influenced terrains constitute an important part of the benthic ecosystems, but they are difficult to detect in large-scale seabed surveys. The areas they occupy are normally small, and survey platforms and sensors allowing high-resolution spatial characterization are necessary. We have developed a cold seep habitat mapping strategy that involves both ship and autonomous underwater vehicle (AUV) as platforms for multibeam echosounder, synthetic aperture sonar (SAS) and a digital photo system. Water column data from the shipborne multibeam echosounder data are initially used to detect gas flares resulting from fluid flow from the seabed. The next phase involves mapping of flare areas by SAS, mounted on an AUV. This yields an acoustic image with a resolution up to 2 cm over a swath of c. 350 m, allowing detection of seep-related features on the seabed. The last phase involves digital photographing of the seabed, with the AUV moving close to the seabed, allowing recognition of bubble streams, seep-related features and giving a first order documentation of the fauna. The strategy was applied to a 3775 km2 large area on the continental shelf, northern Norway. This is a passive continental margin, with thick deposits of oil- and gas-bearing sedimentary rocks. Extensive faulting and tilting of layers provide potential conduits for fluid flow. The seabed is glacially influenced with a highly variable backscatter reflectivity. More than 200 gas flares have been identified, and a similar number of cold seep habitats have been characterized in high spatial detail. Two case studies are shown. In the first area, there is a close spatial relation between active gas seepage and carbonate crust fields. The second case study shows that carbonate crust fields are not necessarily spatially associated with currently active seeps, but represent dormant or formerly active gas expulsion. An important finding is that the bathymetric resolution of shipborne multibeam echosounders will often be too low to detect cold seep habitats. This means that a nested multi-resolution approach involving a multitude of platforms and sensors is required to provide the full pictur

On the use of the HUGIN 1000 HUS Autonomous Underwater Vehicle for high resolution zooplankton measurements

This paper evaluates and tests the HUGIN 1000 HUS AUV as a carrier platform for the Laser Optical Plankton Counter (LOPC). The LOPC was mounted outside on top of the carrier platform, and the tests confirm that this concept did not create turbulence and zooplankton avoidance. A negligible velocity difference between the flow passing through the sampling tube and the AUV speed was detected. The abundance recorded by the LOPC onboard HUGIN 1000 HUS was within the same order of magnitude compared to the zooplankton abundance from traditional net-based measurements. Our results showed zooplankton abundance in the range of 70 to 180 individuals m-3, while other, traditional net-based measurements have indicated 27 - 332 individuals m-3 from the same area and same depth layer. Note that these numbers are minimum and maximum values observed from a vast number of samples. The mean is approximately 200 individuals m-3. The results provide new and unique high-resolution biological data of deep-water copepod communities. The application of AUVs in marine ecological research introduces advanced methodology with potential to address new scientific questions in deep water habitats

Formation of a large submarine crack during the final stage of retrogressive mass wasting on the continental slope offshore northern Norway

High-resolution swath-bathymetry data integrated with sub-bottom profiles and single-channel seismics reveal an 18 km long, up to 1000 m wide and 10-15 m deep crack located approx. 4 km upslope from a slide scar on the continental slope off northern Norway. This crack is formed by subsidence of the sea-floor sediments to a depth of 120 m due to downslope movement of a ~80 km2 large sediment slab that represents the final stage of retrogressive mass wasting in this area. From its morphological freshness, the crack this is inferred to have formed sometime during the last 13 cal. ka BP. These findings add to our understanding of the origin of sea floor cracks on passive continental margins where explanations as slip of normal faults or gas expulsion from the dissociation of gas hydrates previously have been suggested for the formation of cracks in similar settings