The scale of comparative genomics data frequently overwhelms current data visualization methods on conventional (desktop) displays. This paper describes two types of solution that take advantage of wall-sized high-resolution displays (WHirDs), which have orders of magnitude more display real estate (i.e., pixels) than desktop displays. The first allows users to view detailed graphics of copy number variation (CNV) that were output by existing software. A WHirD's resolution allowed a 10× increase in the granularity of bioinformatics output that was feasible for users to visually analyze, and this revealed a pattern that had previously been smoothed out from the underlying data. The second involved interactive visualization software that was innovative because it uses a music score metaphor to lay out CNV data, overcomes a perceptual distortion caused by amplification/deletion thresholds, uses filtering to reduce graphical data overload, and is the first comparative genomics visualization software that is designed to leverage a WHirD's real estate. In a field evaluation, a clinical user discovered a fundamental error in the way their data had been processed, and established confidence in the software by using it to 'find' known genetic patterns in hepatitis C-driven hepatocellular cancer.
):A1-A306 A191 BSG abstracts dependent-magnetic resonance imaging (BOLD-MRI) was used to quantify changes in renal oxygenation. Tissue expression and distribution of RLN receptor (RXFP1) was determined by qPCR and immunofluorescence. Expression of vasoconstrictor genes was quantified by qPCR array. Results RXFP1 was detected on glomerular podocytes, renal pericytes, and endothelial cells of the renal, segmental and interlobar arteries of cirrhotic rats. In CCl 4 cirrhosis, acute i.v. RLN (4µg) induced a 50% increase in RBF after 60 minutes (p < 0.01 vs. placebo, n = 6). BOLD-MRI showed increased tissue oxygenation at the same timepoint in renal cortex and medulla. Extended s.c. RLN increased RBF by 54% in CCl 4 (p < 0.01 vs. placebo, n = 8) and 57% in BDL (p < 0.001 vs. placebo, n = 5) and increased GFR by 138% in CCl 4 (p < 0.01 vs. placebo, n = 8) and 103% in BDL (p < 0.05 vs. placebo, n = 5). Mean arterial pressure was unaffected by RLN. L-NAME (250mg/L) orally (p.o.) abrogated the effect of RLN on RBF and GFR. The relative expression of vasoconstrictor genes in the kidney was markedly reduced by RLN treatment. Conclusion RLN increases RBF in experimental cirrhosis. Crucially, RLN also improves renal function and oxygenation but does not induce systemic hypotension even in decompensated disease. The effects of RLN are mediated via augmentation of NO and downregulation of vasoconstrictor genes known to be important in the pathogenesis of HRS. RLN has potential as a treatment for HRS and further translational studies are warranted. Disclosure of Interest None Declared.
IntroductionCurative therapies improve overall survival by more than 60 months on a small proportion of patients with HCC however the majority of patients are diagnosed with non curable, mostly multi-focal HCC.There are two theories for the development of multifocal HCC. First is intrahepatic metastasis where the new cancer would inherit genetic properties from the index cancer. Second is de novo development of HCC where both cancers are expected to have genetically diverse properties.We aimed to evaluate the presence and frequency of intrahepatic metastasis versus de novo carcinogenesis in HCV related multi-focal HCC.MethodsWe studied DNA copy number profiles of 70 HCV-related hepatocellular cancers found in 19 surgically removed liver specimens from 18 patients.Differences in copy number patterns were objectively analysed using Pearson’s correlations between normalised, non-smoothed, non-segmented ratios (n = 27,180 per each sample). Fisher r to z to r transformation was used in calculation of the average coefficients.ResultsLivers containing 2 or 3 nodules (n = 10 livers) had an average cancer correlation coefficient of 0.395 and only 20% of them (n = 2/10) harboured cancers with coefficients >0.5. Livers containing 4 or more nodules (n = 9 livers) had an average cancer correlation coefficient of 0.620 and 89% of them (n = 8/9) harboured cancers with coefficients >0.5.The higher correlation coefficient may indicate that livers with a larger number of nodules are more likely to harbour genetically similar cancers then liver with a smaller number of nodules. This implies that intrahepatic metastasis starts to occur at a more advanced stage of liver disease and that de novo carcinogenesis takes place at an earlier stage.ConclusionThis study confirms that both processes exist. The occurrence of de novo carcinogenesis leads to emergence of genetically diverse cancers within the same liver. Our data suggests that this occurs at an earlier stage of multifocal spread. Intrahepatic metastasis leads to occurrence of genetically similar cancers within the same liver. This possibly occurs when HCC’s are more established. More cases are needed to validate the sequence of events in hepatocarcinogenesis. This is knowledge is clinically relevant as cancers with diverse genetic profiles are practically more difficult to manage.Disclosure of InterestW. Fateen: None Declared, H. Wood: None Declared, S. Berri Employee of: Illumina, J. Wyatt: None Declared, M. El- Meteini: None Declared, C. Millson: None Declared, P. Quirke: None Declared
IntroductionARFI elastography (virtual touch quantification,VTq™) is a well validated technique for non-invasive assessment of liver fibrosis in viral hepatitis. The interpretation of shear velocity readings in active autoimmune liver disease (AILD) may be affected by a number of factors. However, few studies have specifically examined the effect of inflammation on liver stiffness (LS) in this group. We report the results of a preliminary study in which LS and histology have been sampled simultaneously from the same region of liver tissue in a large cohort with active AILD.MethodsOur local database of 101 patients with AILD (63 autoimmune hepatitis AICH +/- overlap, 38 cholestatic-PBC or PSC) was investigated. LS estimation by ARFI was performed using a standard validated protocol by a single operator. Biopsies were performed from the same region of liver using an 18 G Biopince™ needle, immediately after LS measurement. Clinical, biochemical, ultrasonic and histopathological data were collated retrospectively. ARFI/histological variance (AHV) was defined as a difference of more than 1 Metavir or 2 Ishak stages from that predicted by ARFI, according to standard calibration. 1 ResultsSixty one ARFI + liver biopsies performed at the same session were identified out of a total of 164 ARFI and 114 liver biopsies. Patients included group 1: 37 active AICH (diagnosis/flare on therapy); group 2: 7 AICH remission; and group 3: 17 cholestatic liver disease. Co-pathology was seen in 8. Standard ARFI quality measures were validated in 93%. Mean ARFI shear velocities were significantly higher in group 1 compared with 2 and 3–2.41, 1.29 and 1.64 m/sec, respectively (p = 0.001). AHV occurred in 44.1, 28.6 and 29.4%, AHV prevalence was 41% overall, with 100% in group 1 and 88% overall reflecting overestimation of fibrosis. Across all groups, Ishak necro-inflammatory grade was strongly correlated with both ARFI shear velocity (r = 0.58,p <0.0001) and also AHV (r = 0.35, p = 0.006) by Spearman analysis. ALT showed a weaker correlation with AHV (r = 0.25, p = 0.06).ConclusionThese data show that variance between ARFI shear velocity and histology is common in active AILD, usually overestimating predicted fibrosis stage. Strong positive correlations were seen between histological inflammatory grade with both shear velocity and AHV, suggesting that inflammation is implicated in the observed increase in LS in this group. Confirmation of this association in further studies would suggest a potential role for ARFI elastography in monitoring resolution of inflammation during treatment of AILD.Reference1 D. Sherman, et al. J Hepatol 2014;60(Suppl 1):S413.Disclosure of InterestNone Declared
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