ORCID Profile
0000-0002-7922-3236
Current Organisations
Macquarie University Faculty of Science and Engineering
,
Macquarie University
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Publisher: Springer Science and Business Media LLC
Date: 24-06-2020
Publisher: IOP Publishing
Date: 04-2010
Publisher: Springer Science and Business Media LLC
Date: 05-02-2020
DOI: 10.1038/S41586-020-1969-6
Abstract: 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 1–3 . 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 ex le, 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 4 identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation 5,6 analyses timings and patterns of tumour evolution 7 describes the erse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity 8,9 and evaluates a range of more-specialized features of cancer genomes 8,10–18 .
Publisher: Springer Nature Switzerland
Date: 2023
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 2022
Publisher: Hindawi Limited
Date: 2012
DOI: 10.1155/2012/893040
Abstract: A model with its conductivity varying highly across a very thin layer will be considered. It is related to a stable phantom model, which is invented to generate a certain apparent conductivity inside a region surrounded by a thin cylinder with holes. The thin cylinder is an insulator and both inside and outside the thin cylinderare filled with the same saline. The injected current can enter only through the holes adopted to the thin cylinder. The model has a high contrast of conductivity discontinuity across the thin cylinder and the thickness of the layer and the size of holes are very small compared to the domain of the model problem. Numerical methods for such a model require a very fine mesh near the thin layer to resolve the conductivity discontinuity. In this work, an efficient numerical method for such a model problem is proposed by employing a uniform mesh, which need not resolve the conductivity discontinuity. The discrete problem is then solved by an iterative method, where the solution is improved by solving a simple discrete problem with a uniform conductivity. At each iteration, the right-hand side is updated by integrating the previous iterate over the thin cylinder. This process results in a certain smoothing effect on microscopic structures and our discrete model can provide a more practical tool for simulating the apparent conductivity. The convergence of the iterative method is analyzed regarding the contrast in the conductivity and the relative thickness of the layer. In numerical experiments, solutions of our method are compared to reference solutions obtained from COMSOL, where very fine meshes are used to resolve the conductivity discontinuity in the model. Errors of the voltage in L 2 norm follow O(h) asymptotically and the current density matches quitewell those from the reference solution for a sufficiently small mesh size h . The experimental results present a promising feature of our approach for simulating the apparent conductivity related to changes in microscopic cellular structures.
Publisher: IOP Publishing
Date: 04-2010
Publisher: IOP Publishing
Date: 04-2010
Publisher: IEEE
Date: 11-2021
Publisher: IEEE
Date: 11-2021
Publisher: Springer International Publishing
Date: 2022
Publisher: Wiley
Date: 06-2021
DOI: 10.1002/CPZ1.178
Abstract: Platelets are small but very abundant blood cells that play a key role in hemostasis, contributing to thrombus formation at sites of injury. The ability of platelets to perform this function, as well as functions in immunity and inflammation, is dependent on the presence of cell surface glycoproteins and changes in their quantity and conformation after platelet stimulation. In this article, we describe the characterization of platelet surface markers and platelet function using platelet‐specific fluorescent probes and flow cytometry. Unlike traditional platelet tests, immunophenotypic analysis of platelets by flow cytometry allows the analysis of platelet function in s les with very low platelet counts as often encountered in clinical situations. © 2021 Wiley Periodicals LLC. Basic Protocol 1 : Immunophenotyping of platelet surface receptors Alternate Protocol : Fix‐first method for immunophenotyping of platelet surface receptors Basic Protocol 2 : Determination of platelet activation using P‐selectin expression and/or PAC1 binding Basic Protocol 3 : Determination of procoagulant platelets using annexin V binding or antibodies specific for coagulation factor V/Va or X/Xa Support Protocol : Preparation of isolated platelets
Publisher: IEEE
Date: 05-2011
Publisher: Elsevier BV
Date: 12-2011
Publisher: IEEE
Date: 05-2011
Publisher: Public Library of Science (PLoS)
Date: 17-04-2015
Publisher: Proceedings of the National Academy of Sciences
Date: 26-03-2012
Abstract: Evolutionary change in gene expression is generally considered to be a major driver of phenotypic differences between species. We investigated innate immune ersification by analyzing interspecies differences in the transcriptional responses of primary human and mouse macrophages to the Toll-like receptor (TLR)–4 agonist lipopolysaccharide (LPS). By using a custom platform permitting cross-species interrogation coupled with deep sequencing of mRNA 5′ ends, we identified extensive ergence in LPS-regulated orthologous gene expression between humans and mice (24% of orthologues were identified as “ ergently regulated”). We further demonstrate concordant regulation of human-specific LPS target genes in primary pig macrophages. Divergently regulated orthologues were enriched for genes encoding cellular “inputs” such as cell surface receptors (e.g., TLR6, IL-7Rα) and functional “outputs” such as inflammatory cytokines/chemokines (e.g., CCL20, CXCL13). Conversely, intracellular signaling components linking inputs to outputs were typically concordantly regulated. Functional consequences of ergent gene regulation were confirmed by showing LPS pretreatment boosts subsequent TLR6 responses in mouse but not human macrophages, in keeping with mouse-specific TLR6 induction. Divergently regulated genes were associated with a large dynamic range of gene expression, and specific promoter architectural features (TATA box enrichment, CpG island depletion). Surprisingly, regulatory ergence was also associated with enhanced interspecies promoter conservation. Thus, the genes controlled by complex, highly conserved promoters that facilitate dynamic regulation are also the most susceptible to evolutionary change.
Publisher: Public Library of Science (PLoS)
Date: 25-11-2019
Publisher: Cold Spring Harbor Laboratory
Date: 07-2020
Abstract: Long noncoding RNAs (lncRNAs) constitute the majority of transcripts in the mammalian genomes, and yet, their functions remain largely unknown. As part of the FANTOM6 project, we systematically knocked down the expression of 285 lncRNAs in human dermal fibroblasts and quantified cellular growth, morphological changes, and transcriptomic responses using Capped Analysis of Gene Expression (CAGE). Antisense oligonucleotides targeting the same lncRNAs exhibited global concordance, and the molecular phenotype, measured by CAGE, recapitulated the observed cellular phenotypes while providing additional insights on the affected genes and pathways. Here, we disseminate the largest-to-date lncRNA knockdown data set with molecular phenotyping (over 1000 CAGE deep-sequencing libraries) for further exploration and highlight functional roles for ZNF213-AS1 and lnc-KHDC3L-2 .
Publisher: Wiley
Date: 02-02-2021
DOI: 10.1002/MRM.28685
Abstract: To establish high‐frequency magnetic resonance electrical properties tomography (MREPT) as a novel contrast mechanism for the assessment of glioblastomas using a rat brain tumor model. Six F98 intracranial tumor bearing rats were imaged longitudinally 8, 11 and 14 days after tumor cell inoculation. Conductivity and mean diffusivity maps were generated using MREPT and Diffusion Tensor Imaging. These maps were co‐registered with T 2 ‐weighted images and volumes of interests (VOIs) were segmented from the normal brain, ventricles, edema, viable tumor, tumor rim, and tumor core regions. Longitudinal changes in conductivity and mean diffusivity (MD) values were compared in these regions. A correlation analysis was also performed between conductivity and mean diffusivity values. The conductivity of ventricles, edematous area and tumor regions (tumor rim, viable tumor, tumor core) was significantly higher ( P .01) compared to the contralateral cortex. The conductivity of the tumor increased over time while MD from the tumor did not change. A marginal positive correlation was noted between conductivity and MD values for tumor rim and viable tumor, whereas this correlation was negative for the tumor core. We demonstrate a novel contrast mechanism based on ionic concentration and mobility, which may aid in providing complementary information to water diffusion in probing the microenvironment of brain tumors.
Publisher: Springer Science and Business Media LLC
Date: 05-2011
Publisher: Wiley
Date: 19-11-2018
DOI: 10.1002/MRM.27534
Publisher: IOP Publishing
Date: 04-2010
Publisher: Springer International Publishing
Date: 2022
DOI: 10.1007/978-3-031-03873-0_8
Abstract: This chapter explains the magnetic resonance electrical impedance tomography (MREPT) technique used to image electrical properties at high frequencies. The chapter describes the MREPT data acquisition methods, current state-of-the-art image reconstruction algorithms, and experiments with phantoms, animals, and humans.
Publisher: IEEE
Date: 12-2018
Publisher: Springer International Publishing
Date: 2022
DOI: 10.1007/978-3-031-03873-0_3
Abstract: In this chapter, we will discuss the basic principles of signal generation and image formation in magnetic resonance imaging (MRI). We will start with a description of nuclear magnetic resonance (NMR) phenomenon and then gradually arrive at the mathematical expressions for MRI signal in spatial domain and k-space domain. Then we describe the image reconstruction methods typically used in MRI, the signal-to-noise ratio calculation methods in MRI, and common MR image formats. A key focus of the contents of this chapter is on the formation of phase images in MRI. We do not intend to provide a comprehensive overview of MRI. Instead, the contents are intended for readers interested in performing research in electromagnetic properties mapping using MRI. Nevertheless, considering the generality of the contents, any reader interested in developing a quick understanding of the physical and mathematical background of MRI can find this chapter helpful.
Publisher: The Royal Society
Date: 08-2018
DOI: 10.1098/RSOB.180011
Abstract: The promoters of immediate early genes (IEGs) are rapidly activated in response to an external stimulus. These genes, also known as primary response genes, have been identified in a range of cell types, under erse extracellular signals and using varying experimental protocols. Whereas genomic dissection on a case-by-case basis has not resulted in a comprehensive catalogue of IEGs, a rigorous meta-analysis of eight genome-wide FANTOM5 CAGE (cap analysis of gene expression) time course datasets reveals successive waves of promoter activation in IEGs, recapitulating known relationships between cell types and stimuli: we obtain a set of 57 (42 protein-coding) candidate IEGs possessing promoters that consistently drive a rapid but transient increase in expression over time. These genes show significant enrichment for known IEGs reported previously, pathways associated with the immediate early response, and include a number of non-coding RNAs with roles in proliferation and differentiation. Surprisingly, we also find strong conservation of the ordering of activation for these genes, such that 77 pairwise promoter activation orderings are conserved. Using the leverage of comprehensive CAGE time series data across cell types, we also document the extensive alternative promoter usage by such genes, which is likely to have been a barrier to their discovery until now. The common activation ordering of the core set of early-responding genes we identify may indicate conserved underlying regulatory mechanisms. By contrast, the considerably larger number of transiently activated genes that are specific to each cell type and stimulus illustrates the breadth of the primary response.
Publisher: Springer Science and Business Media LLC
Date: 09-2007
DOI: 10.1038/NG0907-1174B
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 11-2009
Publisher: Springer International Publishing
Date: 2022
DOI: 10.1007/978-3-031-03873-0_1
Abstract: The electromagnetic properties of body tissues depend on numerous factors, the most important of which are ionic concentrations and, particularly in the low-frequency regime, membrane density and geometry. In this chapter, the characteristics of these properties and their spectra are introduced. The properties measured by different types of MR-based methods are described.
Publisher: Springer Science and Business Media LLC
Date: 16-09-2019
DOI: 10.1007/S11307-019-01429-Z
Abstract: Purpose: To establish multi-modal imaging for the assessment of kidney pH, perfusion, and clearance rate using magnetic resonance imaging (MRI) and multispectral optoacoustic tomography (MSOT) in healthy mice. Kidney pH and perfusion values were measured on a pixel-by-pixel basis using the MRI acidoCEST and FAIR-EPI methods. Kidney filtration rate was measured by analyzing the renal clearance rate of IRdye 800 using MSOT. To test the effect of one imaging method on the other, a set of 3 animals were imaged with MSOT followed by MRI, and a second set of 3 animals were imaged with MRI followed by MSOT. In a subsequent study, the reproducibility of pH, perfusion, and renal clearance measurements were tested by imaging 4 animals twice, separated by 4 days. The contrast agents used for acidoCEST based pH measurements influenced the results of MSOT. Specifically, the exponential decay time from the kidney cortex, as measured by MSOT, was significantly altered when MRI was performed prior to MSOT. However, no significant difference in the cortex to pelvis area under the curve (AUC) was noted. When the order of experiments was reversed, no significant differences were noted in the pH or perfusion values. Reproducibility measurements demonstrated similar pH and cortex to pelvis AUC however, perfusion values were significantly different with the cortex values being higher and the pelvic values being lower in the second imaging time. We demonstrate that using a combination of MRI and MSOT, physiological measurements of pH, blood flow, and clearance rates can be measured in the mouse kidney in the same imaging session.
Publisher: IOP Publishing
Date: 10-05-2005
DOI: 10.1088/0967-3334/26/4/014
Abstract: In this paper, we have shown a simple procedure to detect anomalies in the lungs region by electrical impedance tomography. The main aim of the present study is to investigate the possibility of anomaly detection by using neural networks. Radial basis function neural networks are used as classifiers to classify the anomaly as belonging to the anterior or posterior region of the left lung or the right lung. The neural networks are trained and tested with the simulated data obtained by solving the mathematical model equation governing current flow through the simulated thoracic region. The equation solution and model simulation are done with FEMLAB. The effect of adding a higher number of neurons to the hidden layer can be clearly seen by the reduction in classification error. The study shows that there is interaction between the size (radius) and conductivity of anomalies and for some combination of these two factors the classification error of neural networks will be very small.
Publisher: IOP Publishing
Date: 04-2010
Publisher: IEEE
Date: 05-2011
Publisher: IEEE
Date: 05-2011
Publisher: IEEE
Date: 12-2018
Publisher: Public Library of Science (PLoS)
Date: 18-01-2011
Publisher: IOP Publishing
Date: 06-08-2009
DOI: 10.1088/0967-3334/30/9/007
Abstract: Magnetic resonance electrical impedance tomography (MREIT) is a new bio-imaging modality providing cross-sectional conductivity images from measurements of internal magnetic flux densities produced by externally injected currents. Recent experimental results of postmortem and in vivo imaging of the canine brain demonstrated its feasibility by showing conductivity images with meaningful contrast among different brain tissues. MREIT image reconstructions involve a series of data processing steps such as k-space data handling, phase unwrapping, image segmentation, meshing, modelling, finite element computation, denoising and so on. To facilitate experimental studies, we need a software tool that automates these data processing steps. In this paper, we summarize such an MREIT software package called CoReHA (conductivity reconstructor using harmonic algorithms). Performing imaging experiments of the postmortem canine abdomen, we demonstrate how CoReHA can be utilized in MREIT. The abdomen with a relatively large field of view and various organs imposes new technical challenges when it is chosen as an imaging domain. Summarizing a few improvements in the experimental MREIT technique, we report our first conductivity images of the postmortem canine abdomen. Illustrating reconstructed conductivity images, we discuss how they discern different organs including the kidney, spleen, stomach and small intestine. We elaborate, as an ex le, that conductivity images of the kidney show clear contrast among cortex, internal medulla, renal pelvis and urethra. We end this paper with a brief discussion on future work using different animal models.
Publisher: Springer Science and Business Media LLC
Date: 02-2011
Publisher: Springer Science and Business Media LLC
Date: 03-2014
DOI: 10.1038/NATURE13182
Publisher: IEEE
Date: 08-2008
Publisher: Springer Science and Business Media LLC
Date: 27-05-2012
DOI: 10.1038/NG.2293
Publisher: IEEE
Date: 07-2017
Publisher: IEEE
Date: 09-2009
Publisher: Wiley
Date: 05-03-2018
DOI: 10.1002/MRM.27145
Publisher: IOP Publishing
Date: 16-03-2011
DOI: 10.1088/0031-9155/56/7/022
Abstract: Magnetic resonance electrical impedance tomography (MREIT) aims to produce high-resolution cross-sectional images of conductivity distribution inside the human body. Injected current into an imaging object induces a distribution of internal magnetic flux density, which is measured by using an MRI scanner. We can reconstruct a conductivity image based on its relation with the measured magnetic flux density. In this paper, we explain the contrast mechanism in MREIT by performing and analyzing a series of numerical simulations and imaging experiments. We built a stable conductivity phantom including a hollow insulating cylinder with holes. Filling both inside and outside the hollow cylinder with the same saline, we controlled ion mobilities to create a conductivity contrast without being affected by the ion diffusion process. From numerical simulations and imaging experiments, we found that slopes of induced magnetic flux densities change with hole diameters and therefore conductivity contrasts. Associating the hole diameter with apparent conductivity of the region inside the hollow cylinder with holes, we could experimentally validate the contrast mechanism in MREIT. Interpreting reconstructed apparent conductivity images of the phantom as ion mobility images, we discuss the meaning of the apparent conductivity seen by a certain probing method. In designing MREIT imaging experiments, the ion mobility imaging method using the proposed stable conductivity phantom will enable us to estimate a distinguishable conductivity contrast for a given set of imaging parameters.
Publisher: American Association for Cancer Research (AACR)
Date: 15-11-2019
DOI: 10.1158/0008-5472.CAN-19-0037
Abstract: This study provides a useful model for MITF-low melanomas and MITF-independent cell populations that can be used to study the mechanisms that drive these tumors as well as identify potential therapeutic options.
Publisher: Wiley
Date: 25-03-2011
DOI: 10.1002/MRM.22872
Abstract: Latest experimental results in magnetic resonance electrical impedance tomography (MREIT) demonstrated high-resolution in vivo conductivity imaging of animal and human subjects using imaging currents of 5 to 9 mA. Externally injected imaging currents induce magnetic flux density distributions, which are affected by a conductivity distribution. Since we extract the induced magnetic flux density images from MR phase images, it is essential to reduce noise in the phase images. In vivo human and disease model animal experiments require reduction of imaging current litudes and scan times. In this article, we investigate a multi-echo based MREIT pulse sequence where we utilize a remaining time after the first echo within one TR to obtain more echo signals. It also allows us to prolong the total current injection time. From phantom and animal imaging experiments, we found that this method significantly reduces the noise level in measured magnetic flux density images. We describe experimental validation of the multi-echo sequence by comparing its performance with a single-echo method using 3 mA imaging currents. The proposed method will be advantageous for an imaging region with long T2 values such as the brain and knee. Depending on T2 values, we suggest using two or three echoes in future experimental studies.
Location: Australia
No related grants have been discovered for Atul Singh Minhas.