Mudassar Iqbal

Mudassar Iqbal
The University of Manchester · Faculty of Biology, Medicine and Health

PhD

About

78
Publications
5,370
Reads
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624
Citations
Introduction
Mudassar Iqbal currently works in the Division of Informatics, Imaging and Data Sciences, Faculty of Biology, Medicine and Health, University of Manchester. Mudassar does research in Computational and Systems Biology. Their current project is 'Deciphering the role of p63 in secondary palate development using systems biology.'
Additional affiliations
April 2011 - January 2014
University of Nottingham
Position
  • Research Associate
November 2008 - March 2011
The University of Warwick
Position
  • Research Associate
November 2004 - October 2008
University of Kent
Position
  • PhD Student

Publications

Publications (78)
Article
The physiology and pathology of the skin are influenced by daily oscillations driven by a master clock located in the brain, and peripheral clocks in individual cells. The pathogenesis of psoriasis is circadian‐rhythmic, with flares of disease and symptoms such as itch typically being worse in the evening / night‐time. Patients with psoriasis have...
Article
Full-text available
The glucocorticoid receptor (GR) is a nuclear receptor critical to the regulation of energy metabolism and inflammation. The actions of GR are dependent on cell type and context. Here, we demonstrate the role of liver lineage-determining factor hepatocyte nuclear factor 4A (HNF4A) in defining liver specificity of GR action. In mouse liver, the HNF4...
Article
Many biological studies of transcriptional control mechanisms produce lists of genes and non-coding genomic intervals from corresponding gene expression and epigenomic assays. In higher organisms, such as eukaryotes, genes may be regulated by distal elements, with these elements lying 10s–100s of kilobases away from a gene transcription start site....
Article
Full-text available
The circadian clock component NR1D1 (REVERBα) is considered a dominant regulator of lipid metabolism, with global Nr1d1 deletion driving dysregulation of white adipose tissue (WAT) lipogenesis and obesity. However, a similar phenotype is not observed under adipocyte-selective deletion ( Nr1d1 Flox2-6 :Adipoq Cre ), and transcriptional pro1ling demo...
Article
Full-text available
Many biological studies of transcriptional control mechanisms produce lists of genes and non-coding genomic intervals from corresponding gene expression and epigenomic assays. In higher organisms, such as eukaryotes, genes may be regulated by distal elements, with these elements lying 10s–100s of kilobases away from a gene transcription start site....
Preprint
Full-text available
The glucocorticoid receptor (GR) is a nuclear hormone receptor critical to the regulation of energy metabolism and the inflammatory response. The actions of GR are highly dependent on cell type and environmental context. Here, we demonstrate the necessity for liver lineage-determining factor hepatocyte nuclear factor 4A (HNF4A) in defining liver-sp...
Article
Full-text available
Chronic hepatitis B virus (HBV) infection is a major cause of liver disease and cancer worldwide for which there are no curative therapies. The major challenge in curing infection is eradicating or silencing the covalent closed circular DNA (cccDNA) form of the viral genome. The circadian factors BMAL1/CLOCK and REV-ERB are master regulators of the...
Article
Full-text available
The nuclear receptor REVERBα is a core component of the circadian clock and proposed to be a dominant regulator of hepatic lipid metabolism. Using antibody-independent ChIP-sequencing of REVERBα in mouse liver, we reveal a high-confidence cistrome and define direct target genes. REVERBα-binding sites are highly enriched for consensus RORE or RevDR2...
Preprint
Full-text available
The circadian clock component REVERBα is considered a dominant regulator of lipid metabolism, with global Reverbα deletion driving dysregulation of white adipose tissue (WAT) lipogenesis and obesity. However, a similar phenotype is not observed under adipocyte-selective deletion ( Reverbα Flox2-6 Adipo Cre ), and transcriptional profiling demonstra...
Article
Full-text available
Glucocorticoids (GCs) act through the glucocorticoid receptor (GR, also known as NR3C1) to regulate immunity, energy metabolism and tissue repair. Upon ligand binding, activated GR mediates cellular effects by regulating gene expression, but some GR effects can occur rapidly without new transcription. Here, we show that GCs rapidly inhibit cell mig...
Article
Full-text available
Efficient mitochondrial function is required in tissues with high energy demand such as the heart, and mitochondrial dysfunction is associated with cardiovascular disease. Expression of mitochondrial proteins is tightly regulated in response to internal and external stimuli. Here we identify a novel mechanism regulating mitochondrial content and fu...
Article
Full-text available
The circadian clock regulates many aspects of immunity. Bacterial infections are affected by time of day, but the mechanisms involved remain undefined. Here we show that loss of the core clock protein BMAL1 in macrophages confers protection against pneumococcal pneumonia. Infected mice show both reduced weight loss and lower bacterial burden in cir...
Preprint
Full-text available
Embryonic stem cells (ESCs) are pluripotent in nature, meaning that they have the capacity to differentiate into any cell in the body. However, to do so they must transition through a series of intermediate cell states before becoming terminally differentiated. A lot is known about how ESCs maintain their pluripotent state but comparatively less ab...
Article
Full-text available
The glucocorticoid receptor (GR) is a major drug target in inflammatory disease. However, chronic glucocorticoid (GC) treatment leads to disordered energy metabolism, including increased weight gain, adiposity, and hepatosteatosis — all programs modulated by the circadian clock. We demonstrated that while antiinflammatory GC actions were maintained...
Article
Embryonic stem cells (ESCs) must transition through a series of intermediate cell states before becoming terminally differentiated. Here, we investigated the early events in this transition by determining the changes in the open chromatin landscape as naive mouse ESCs transition to epiblast-like cells (EpiLCs). Motif enrichment analysis of the newl...
Article
Full-text available
We have developed a machine learning approach to predict stimulation-dependent enhancer-promoter interactions using evidence from changes in genomic protein occupancy over time. The occupancy of estrogen receptor alpha (ERα), RNA polymerase (Pol II) and histone marks H2AZ and H3K4me3 were measured over time using ChIP-Seq experiments in MCF7 cells...
Data
Performance of the enhancer-gene (300 bp upstream + gene) model on even chromosomes - all combinations Figure shows the comparison of performance of the NB model on even chromosomes (test data) measured by Precision-TPR and MAP scores. The Precision-TPR curves show the accuracy of the predictions with the highest 10%, 20%, 30% scores i.e. posterior...
Data
Performance of the enhancer-gene (1,500 bp upstream + gene) model on even chromosomes - all combinations Figure shows the comparison of performance of the NB model on even chromosomes (test data) measured by Precision-TPR and MAP scores. The Precision-TPR curves show the accuracy of the predictions with the highest 10%, 20%, 30% scores i.e. posteri...
Data
Complete list of predictions of the model
Data
Process of merging individual MACS-called peaks Cartoon shows the process of merging individual MACS-called peaks with the objective of finding approximate locations of time persistent ER-α bindings. In the process MACS-detected time varying peaks from [0], 5, . . . , 320 min time points (0 is optional and by default not included) which co-occur at...
Data
Histograms of positive and negative features between genes (1,500 bp upstream + gene) and enhancers—odd chromosomes The graphs (A–D) show positive (green) and negative (yellow) distributions of correlations between time series of 300 bp-upstream-extended- gene regions and enhancer bodies for ER- α, PolII, H2AZ and H3K4me3 collected across all odd c...
Data
Performance of the enhancer-gene (300 bp upstream + gene) model on odd chromosomes - all combinations Figure shows the comparison of performance of the NB model on odd chromosomes (training data) measured by Precision-TPR and MAP scores. The Precision-TPR curves show the accuracy of the predictions with the highest 10%, 20%, 30% scores i.e., poster...
Data
Joint clustering of PolII and ER with AP Figure shows the clustering of the joint time course of Pol II and ER-α at enhancers with Affinity Propagation. The clustering involves only the time series which individually possess a sum of at least 200 tags across all time point.
Data
Performance of the enhancer-gene (300 p upstream + gene) model on even chromosomes—varying number of time points Figure shows the comparison of performance of the NB model on even chromosomes (test data) with correlation-based features calculated using the first (a) 8, (b) 6, (c) 4 time points of our logarithmically spaced time course data. The per...
Data
Histograms of positive and negative features between genes (300 bp upstream + gene) and enhancers—all chromosomes The graphs (A–D) show positive (green) and negative (yellow) distributions of correlations between time series of 300 bp-upstream-extended- gene regions and enhancer bodies for ER- α, PolII, H2AZ and H3K4me3 collected across all 23 chro...
Data
Performance of the enhancer-gene (1,500 bp upstream + gene) model on odd chromosomes - all combinations Figure shows the comparison of performance of the NB model on odd chromosomes (training data) measured by Precision-TPR and MAP scores. The Precision-TPR curves show the accuracy of the predictions with the highest 10%, 20%, 30% scores i.e. poste...
Data
Performance on odd chromosomes for alternative MACS parametrisation; (1e−07, λ local off ) vs (1e−05, λ local on) The first column of the figure shows the performance of the NB model on all odd chromosomes. The model was trained on the stringent time persistent merged MACS-called peaks (i.e., distal ER-α bindings) from the scan with the p- value of...
Data
Performance on even chromosomes for alternative MACS parametrisation; (1e−07, λ local off) vs (1e−05, λ local on) The first column of the figure shows the performance of the NB model on all even chromosomes. The model was trained on the stringent time persistent merged MACS-called peaks (i.e., distal ER-α bindings) from the scan with the p-value of...
Data
Histograms of positive and negative features between genes (300 bp upstream + gene) and enhancers (lambda on, 10e−05)—odd chromosomes The graphs (a, b, c, d) show positive (green) and negative (yellow) distributions of correlations between time series of 300 bp-upstream-extended- gene regions and enhancer bodies (MACS: λ local on, p-value 10e−05) f...
Article
Full-text available
The glucocorticoid receptor (GR) is essential for the stress response in mammals. We investigated potential non-transcriptional roles of GR in cellular stress response using fission yeast as a model.We surprisingly discovered marked heat stress resistance in yeast ectopically expressing human GR, which required expression of both the N-terminal tra...
Article
Full-text available
The bacterial Lux system is used as a gene expression reporter. It is fast, sensitive and non-destructive, enabling high frequency measurements. Originally developed for bacterial cells, it has also been adapted for eukaryotic cells, and can be used for whole cell biosensors, or in real time with live animals without the need for euthanasia. Howeve...
Data
The file S1 Text contains detailed methods of the computational modelling, including reactions mechanisms and related velocity derivations, and details for parameter estimation for all three reactions (Fre, LuxAB, and LuxEC), including relevant sub-models, additional figures for model data fits, diagnostic figures for MCMC methods, details of poste...
Article
Full-text available
Motivation: Regulation of gene expression in prokaryotes involves complex co-regulatory mechanisms involving large numbers of transcriptional regulatory proteins and their target genes. Uncovering these genome-scale interactions constitutes a major bottleneck in systems biology. Sparse latent factor models, assuming activity of transcription facto...
Preprint
Full-text available
We have developed a machine learning approach to predict context specific enhancer-promoter interactions using evidence from changes in genomic protein occupancy over time. The occupancy of estrogen receptor alpha (ERα), RNA polymerase (Pol II) and histone marks H2AZ and H3K4me3 were measured over time using ChIP-Seq experiments in MCF7 cells stimu...
Preprint
Full-text available
We have developed a machine learning approach to predict context specific enhancer-promoter interactions using evidence from changes in genomic protein occupancy over time. The occupancy of estrogen receptor alpha (ERα), RNA polymerase (Pol II) and histone marks H2AZ and H3K4me3 were measured over time using ChIP-Seq experiments in MCF7 cells stimu...
Preprint
Full-text available
The bacterial Lux system is used as a gene expression reporter. It is fast, sensitive and non-destructive, enabling high frequency measurements. Originally developed for bacterial cells, it has been adapted for eukaryotic cells, and can be used for whole cell biosensors, or in real time with live animals without the need for slaughter. However, cor...
Article
Full-text available
In plants, the generation of new cell types and tissues depends on coordinated and oriented formative cell divisions. The plasma membrane-localized receptor kinase ARABIDOPSIS CRINKLY 4 (ACR4) is part of a mechanism controlling formative cell divisions in the Arabidopsis root. Despite its important role in plant development, very little is known ab...
Article
Full-text available
Zinc is essential for life, but toxic in excess. Thus all cells must control their internal zinc concentration. We used a systems approach, alternating rounds of experiments and models, to further elucidate the zinc control systems in Escherichia coli. We measured the response to zinc of the main specific zinc import and export systems in the wild-...
Article
Full-text available
Tight junctions (TJs) link adjacent cells and are critical for maintenance of apical-basolateral polarity in epithelial monolayers. The TJ protein occludin functions in disparate processes, including wound healing and Hepatitis C Virus infection. Little is known about steady-state occludin trafficking into and out of the plasma membrane. Therefore,...
Article
Proteins interact with each other to perform an array of cellular functions. A systems-level knowledge of protein interaction networks, as well as the underlying domain-domain interactions, constitutes a major goal in systems biology. In this mini-review, we discuss some background to the problem of inference of domain-domain interactions and brief...
Article
Full-text available
Determining transcriptional regulator activities is a major focus of systems biology, providing key insight into regulatory mechanisms and co-regulators. For organisms such as Escherichia coli, transcriptional regulator binding site data can be integrated with expression data to infer transcriptional regulator activities. However, for most organism...
Article
Full-text available
Following successful completion of the Brassica rapa sequencing project, the next step is to investigate functions of individual genes/proteins. For Arabidopsis thaliana, large amounts of protein-protein interaction (PPI) data are available from the major PPI databases (DBs). It is known that Brassica crop species are closely related to A. thaliana...
Article
Full-text available
During the lifetime of a fermenter culture, the soil bacterium S. coelicolor undergoes a major metabolic switch from exponential growth to antibiotic production. We have studied gene expression patterns during this switch, using a specifically designed Affymetrix genechip and a high-resolution time-series of fermenter-grown samples. Surprisingly, w...
Article
Full-text available
Background: During the lifetime of a fermenter culture, the soil bacterium S. coelicolor undergoes a major metabolic switch from exponential growth to antibiotic production. We have studied gene expression patterns during this switch, using a specifically designed Affymetrix genechip and a high-resolution time-series of fermenter-grown samples.
Data
Validation of the expression data by qRT-PCR. Black lines show the array data, red lines indicate the corresponding PCR measurements.
Data
Description of individual genes in the clusters shown in Figures 2, 3, 4, 5, 6, 7, 8, 9. The columns specify the SCO gene identifier, the gene name (if available), a brief description of the gene's function and the normalized expression value of the corresponding microarray probe set for each time point.
Chapter
Full-text available
We propose a new hybrid data mining method for predicting protein-protein interactions combining Likelihood-Ratio with rule induction algorithms. In essence, the new method consists of using a rule induction algorithm to discover rules representing partitions of the data, and then the discovered rules are interpreted as “bins” which are used to com...
Article
Full-text available
Cellular processes often hinge upon specific interactions among proteins, and knowledge of these processes at a system level constitutes a major goal of proteomics. In particular, a greater understanding of protein-protein interactions can be gained via a more detailed investigation of the protein domain interactions that mediate the interactions o...
Conference Paper
Full-text available
Many processes in the cell involve interaction among the proteins and determination of the networks of such interactions is of immense importance towards the complete understanding of cellular functions. As the experimental techniques for this purpose are expensive and potentially erroneous, there are many computational methods being put forward fo...
Conference Paper
Full-text available
In this paper we present an estimation of distribution par- ticle swarm optimization algorithm that borrows ideas from recent de- velopments in ant colony optimization which can be considered an es- timation of distribution algorithm. In the classical particle swarm opti- mization algorithm, particles exploit their individual memory to explore the...