Fios Genomics (United Kingdom)

A WSe2 field effect transistor integrated with a lead zirconium titanate (PZT) pyroelectric device has been designed, fabricated, and tested and is described as the integrated pyroelectric device. The integrated device has been compared to a standalone pyroelectric device, which consists of PZT sandwiched between platinum electrodes. A pyroelectric coefficient of 1.755 × 10−4 C/m2K has been realized for our thin-film PZT (650 nm). The integrated device amplifies the output of the standalone device by over ten orders of magnitude as the current density calculated for the devices is 16 nA/mm2 and 1 nA/mm2, respectively. The interplay between the pyro- and ferro-induced polarization of the integrated device has been studied. From our observations, the ferroelectric gating controls directly the drain-source current output of the integrated device, showing anti-clockwise hysteresis behavior. The device shows promise for application in infrared sensing.

Obstructive sleep apnoea (OSA), a condition characterised by intermittent hypoxia and reoxygenation during sleep, is associated with an increased risk of adverse pregnancy outcomes including gestational diabetes and hypertensive disorders of pregnancy. The biological mechanisms of these associations are poorly understood. The impact of OSA on placental function has not been well characterised. We performed 3' mRNA sequencing on placenta from women with obesity and OSA (n=11) and women with obesity and no OSA (n=9). After correcting for multiple testing, there were no statistically significant differences in gene expression between OSA and no OSA groups (adjusted p<0.05). In unadjusted analyses, 101 genes were differentially expressed in OSA compared to no OSA placentae (p<0.01). In Reactome pathway and GO term analysis, this included downregulation of genes involved in O-linked glycosylation (B3GNT5 and B3GNT8) and Wnt signalling (TRABD2B and FRZB) pathways. In gene set enrichment analysis, genes within 24 pathways had a non-random distribution in OSA compared to no OSA placentae (adjusted p<0.05). This included an increase in genes relating to the reversible hydration of carbon dioxide in OSA placentae, a potential novel mechanism contributing to the development of adverse pregnancy outcomes in women with OSA. There is overall similarity in the placental transcriptome of women with obesity who do and do not have OSA during pregnancy. Alterations in the reversible hydration of carbon dioxide are a potential mechanism contributing to the development of adverse pregnancy outcomes in maternal OSA, however this finding requires validation in larger cohorts.

Here we describe a collaboration between industry, the National Health Service (NHS) and academia that sought to demonstrate how early understanding of both pharmacology and genomics can improve strategies for the development of precision medicines. Diseased tissue ethically acquired from patients suffering from chronic obstructive pulmonary disease (COPD), was used to investigate inter-patient variability in drug efficacy using ex vivo organocultures of fresh lung tissue as the test system. The reduction in inflammatory cytokines in the presence of various test drugs was used as the measure of drug efficacy and the individual patient responses were then matched against genotype and microRNA profiles in an attempt to identify unique predictors of drug responsiveness. Our findings suggest that genetic variation in CYP2E1 and SMAD3 genes may partly explain the observed variation in drug response.

Introduction: Prostate cancer (PrCa) is the second leading cause of cancer death in men. Despite having a lower tumor mutation burden (TMB) than most tumor types (1), multiple gene fusions such as TMPRSS2-ERG have been characterized in prostate cancer and have been linked to aggressive disease (1). Individual tumor samples may contain multiple fusions and it is unknown whether these fusions could increase tumor immunogenicity. Here we investigated the effects of fusion burden on the expression of key molecular and immune effectors in prostate cancer specimens representing different stages of disease progression and androgen sensitivity (hormone sensitive vs metastatic castrate resistant prostate cancer (mCRPC)).Methods: 187 prostate samples taken from different stages of PrCa including Early/intermediate (n:30), late (n:112) and metastatic disease (n:9) were interrogated by RNASeq and assessed for mutation burden (mutations/MB of the genome) and fusion burden (number of fusions/10,000 genes profiled in each sample). To characterize the immune microenvironment, stromal TILS, % immune infiltrate, CD8+ T-cells, and PDL-1 expression were assessed by immunohistochemistry (IHC). Key molecular and immune gene signatures derived from the expression data were clustered according to disease stage, mutation or fusion burden, and hormone sensitive vs mCRPC disease (determined by mCRPC score from (2)).Results and Conclusion: TMB was very low across all samples analyzed (0.01-1.2 mutations per MB) while fusion burden ranged from 0 to 34 fusions/10,000 genes (up to 70 fusion(s) per sample) and was inversely correlated to TMB and not associated with disease stage. High fusion burden across samples correlated with high cell cycle progression and AR signaling (P<0.0001), ERG and ETS transcriptional activity (P<0.005) along with a modest increase in stromal TILs, % immune infiltrate and PDL-1 expression on immune cells. Fusion burden also correlated with immune signatures representing activation of M1 macrophages, checkpoint inhibitors, and T-cell activity (IFNγ-induced and T-effector signatures) (P<0.0001) whilst inversely correlating with an immune suppressor signature (P<0.01). High fusion burden also correlated with a high mCRPC score (P<0.0001), representing the most aggressive disease. Samples with a high mCRPC score also had gene signature scores suggesting high AR signaling, PI3K signaling, cell cycle progression and class I antigen presentation, and low expression of neuroendocrine tumor markers, NK cell and immune suppressor signatures. Our data suggest that high fusion burden may be associated more closely with immunogenicity and disease prognosis than TMB in PrCa and that tumors with high fusion burden could be potential candidates for immunotherapy. References(1) Chalmers et al. (2017), Genome Medicine Apr 19: 9(1):34 9:34.(2) Sharma N.L et al. (2013), Cancer Cell: Jan 14: 23(1):35-47.Note: This abstract was not presented at the meeting.Citation Format: Marie Wagle, Kobe Yuen, Edward E. Kadel, Thomas Holcomb, Shrividhya Srinivasan, Joseph Castillo, Dan Halligan, Adrian Carr, Max Bylesjo, Julian Augley, Simone Daminelli, Mark Kockx, Yannick Waumans, Jennifer Giltnane, Zineb Mounir. Association of tumor fusion burden with immune presence and androgen sensitivity in prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2149.

Summaryheatmaply is an R package for easily creating interactive cluster heatmaps that can be shared online as a stand-alone HTML file. Interactivity includes a tooltip display of values when hovering over cells, as well as the ability to zoom in to specific sections of the figure from the data matrix, the side dendrograms, or annotated labels. Thanks to the synergistic relationship between heatmaply and other R packages, the user is empowered by a refined control over the statistical and visual aspects of the heatmap layout.Availability and implementationThe heatmaply package is available under the GPL-2 Open Source license. It comes with a detailed vignette, and is freely available from: http://cran.r-project.org/package=heatmaply.Supplementary informationSupplementary data are available at Bioinformatics online.

A device for a low-to-intermediate level of gesture recognition which uses a passive thermal-infrared (PIR) sensor array is described. The detection system which discriminates between a small number of simple dynamic gestures, such as ‘hand swiping’ in different directions and at varying velocities. The technology is low powered, in terms of energy consumption and computational power. The sensor enables a gesture sensing input, for mobile device application areas, where hands-free operation can be useful and where low-power consumption is essential.

Metabonomics aims to identify and quantify all small-molecule metabolites in biologically relevant samples using high-throughput techniques such as NMR and chromatography/mass spectrometry. This generates high-dimensional data sets with properties that require specialized approaches to data analysis. This chapter describes multivariate statistics and analysis tools to extract meaningful information from metabonomic data sets. The focus is on the use and interpretation of latent variable methods such as principal component analysis (PCA), partial least squares/projections to latent structures (PLS), and orthogonal PLS (OPLS). Descriptions of the key steps of the multivariate data analyses are provided with demonstrations from example data.

A sensing device for a touchless, hand gesture, user interface based on an inexpensive passive infrared pyroelectric detector array is presented. The 2 x 2 element sensor responds to changing infrared radiation generated by hand movement over the array. The sensing range is from a few millimetres to tens of centimetres. The low power consumption (