Project description:RNA sequencing of human leukemia The goals of this project are to obtain a comprehensive study of mutations and gene expression in human acute myeloid leukemia (AML). Methods: AML cells were thawed. DNA and RNA (polyA) was extracted and sequences were obtained with an Illumina HiSeq 2000 sequencer.
Project description:RNA sequencing of human leukemia The goals of this project are to obtain a comprehensive study of mutations and gene expression in human acute myeloid leukemia (AML). Methods: AML cells were thawed. DNA and RNA (polyA) was extracted and sequences were obtained with an illumina HiSeq 2000 sequencer. Results are pending.
Project description:RNA sequencing of human leukemia The goals of this project are to obtain a comprehensive study of mutations and gene expression in human acute myeloid leukemia (AML). Methods: AML cells were thawed. DNA and RNA (polyA) was extracted and sequences were obtained with an illumina HiSeq 2000 sequencer. Results are pending.
Project description:RNA sequencing of human leukemia The goals of this project are to obtain a comprehensive study of mutations and gene expression in human acute myeloid leukemia (AML). Methods: AML cells were thawed. DNA and RNA (polyA) was extracted and sequences were obtained with an illumina HiSeq 2000 sequencer. Results are pending.
Project description:RNA sequencing of human leukemia The goals of this project are to obtain a comprehensive study of mutations and gene expression in human acute myeloid leukemia (AML). Methods: AML cells were thawed. DNA and RNA (polyA) was extracted and sequences were obtained with an illumina HiSeq 2000 sequencer. Results are pending.
Project description:This is a continuation of the Chordoma Sequencing Project. All cancers arise due to somatically acquired abnormalities in DNA sequence. Systematic sequencing of cancer genomes allows acquisition of complete catalogues of all classes of somatic mutation present in cancer. These mutation catalogues will allow identification of the somatically mutated cancer genes that are operative and characterise patterns of somatic mutation that may reflect previous exogenous and endogenous mutagenic exposures. In this application, we aim to perform whole genome sequencing on 10 chordoma matched genome pairs. RNA Sequencing/Methylation and SNP6 and an additional sequencing of three cancer cell lines will be added to this work.
Project description:Normal Karyotype acute myeloid leukemia (NK-AML) represents approximately 50% of all cases of AML which patients develop. Most AML cell lines are highly abnormal and therefore not good models for investigating NK-AML biology a novel AML cell line, CG-SH, was recently estabished and here we characterize the gene expression and mutations present through high-throughput sequencing of RNA and genomic DNA using a HiSeq 2000 The overall design of the experiment was to characterize, at single base pair resolution, all of the genetic defects present in a novel normal karyotype cell line, CG-SH
Project description:The paper describes a model of acute myeloid leukaemia.
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This model is described in the article:
Optimal control of acute myeloid leukaemia
Jesse A. Sharp, Alexander P Browning, Tarunendu Mapder, Kevin Burrage, Matthew J Simpson
Journal of Theoretical Biology 470 (2019) 30–42
Abstract:
Acute myeloid leukaemia (AML) is a blood cancer affecting haematopoietic stem cells. AML is routinely treated with chemotherapy, and so it is of great interest to develop optimal chemotherapy treatment strategies. In this work, we incorporate an immune response into a stem cell model of AML, since we find that previous models lacking an immune response are inappropriate for deriving optimal control strategies. Using optimal control theory, we produce continuous controls and bang-bang controls, corre- sponding to a range of objectives and parameter choices. Through example calculations, we provide a practical approach to applying optimal control using Pontryagin’s Maximum Principle. In particular, we describe and explore factors that have a profound influence on numerical convergence. We find that the convergence behaviour is sensitive to the method of control updating, the nature of the control, and to the relative weighting of terms in the objective function. All codes we use to implement optimal control are made available.
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Project description:We exploited the extensive genomic diversity of the Leucegene cohort of primary human AML specimens to provide an overview of the human AML surfaceome. Due to high cell number requirements, surface proteomics has been underexploited in AML so far, although surface proteome analysis of AML cell lines and small cohorts of primary human AML specimens paved the way for antigen identification23-25. Herein, we compared global and surface proteomic datasets generated from primary human AML specimens and show that surfaceome analysis uniquely identifies a larger subset of cell surface proteins compared to global proteomics. We therefore built a cohort of 100 primary human AML specimens that was subjected to surface proteome analysis and served as a primary dataset for antigen identification. A significant portion of the cohort also underwent single-cell RNA sequencing, which allowed the exploration of antigen expression at the population level and the selection of AML antigens expressed by primitive blasts. These analyses led to the identification of novel AML antigens expressed by the majority of AML specimens of the cohort, of antigens overexpressed by specific AML subgroups, as well as of previously uncovered potential leukemia stem cell (LSC) markers, and represents the first large-scale surface proteomic study in AML.