Mahmoud Ahmed

Institute of Cancer Research · Division of Genetics and Epidemiology

Background: Transcription factor binding to the regulatory region of a gene induces or represses its gene expression. Transcription factors share their binding sites with other factors, co-factors and/or DNA-binding proteins. These proteins form complexes which bind to the DNA as one-units. The binding of two factors to a shared site does not alwa...

Screening for potential cancer therapies using existing large datasets of drug perturbations requires expertise and resources not available to all. This is often a barrier for lab scientists to tap into these valuable resources. To address these issues, one can take advantage of prior knowledge especially those coded in standard formats such as cau...

Differentiating 3T3-L1 pre-adipocytes are a mixture of non-identical culture cells. It is vital to identify the cell types that respond to the induction stimulus to understand the pre-adipocyte potential and the mature adipocyte behavior. To test this hypothesis, we deconvoluted the gene expression profiles of the cell culture of MDI-induced 3T3-L1...

We previously showed that some adipogenic transcription factors such as CEBPB and PPARG directly and indirectly regulate autophagy gene expression in adipogenesis. The order and effect of these events are undetermined. In this study, we modeled the gene expression, DNA-binding of transcriptional regulators, and histone modifications during adipocyt...

Background Real-time quantitative PCR (qPCR) is a broadly used technique in the biomedical research. Currently, few different analysis models are used to determine the quality of data and to quantify the mRNA level across the experimental conditions. Methods We developed an R package to implement methods for quality assessment, analysis and testin...

Transcription factor binding to a gene regulatory region induces or represses its expression. Binding and expression target analysis (BETA) integrates the binding and gene expression data to predict this function. First, the regulatory potential of the factor is modeled based on the distance of its binding sites from the transcription start sites i...

Breast cancer is a common tumor type among women, with a high fatality due to metastasis. Metastasis suppressors encode proteins that inhibit the metastatic cascade independent of the primary tumor growth. Raf kinase inhibitory protein (RKIP) is one of the promising metastasis suppressor candidates. RKIP is reduced or lost in aggressive variants of...

The human genome project galvanized the scientific community around an ambitious goal. Upon completion, the project delivered several discoveries, and a new era of research commenced. More importantly, novel technologies and analysis methods materialized during the project period. The cost reduction allowed many more labs to generate high-throughpu...

Ob/ob mice are leptin-deficient animals with uninhibited food intake and susceptibility to gain weight and develop type 2 diabetes. The mice have been used to study obesity and diabetes. We generated a dataset of different tissue gene expressions from wild-type and ob/ob mice with a normal diet (ND) or high-fat diet (HFD). The gene expression was p...

Obesity is a widespread health issue worldwide. Therefore, evaluating existing pharmaceuticals and developing new effective strategies to mitigate the problem is essential. Although literature reviews of a broad range of interventions for managing obesity exist, a recent evaluation of the efficacy of orlistat is lacking. This meta-analysis aims to...

Transcription factor binding to a gene regulatory region induces or represses its expression. Binding and expression target analysis (BETA) integrates the binding and gene expression data to predict this function. First, the regulatory potential of the factor is modeled based on the distance of its binding sites from the transcription start sites i...

Metastasis is associated with poor prognosis and is the major cause of death in cancer patients. The epithelial to mesenchymal transition (EMT) is essential for cancer cells to acquire a highly migratory phenotype. Metabolic reprogramming is required to meet the energy demands during this process. Recent studies have indicated that autophagy is inv...

Intervertebral disc degeneration (IVDD) is a prevalent cause of low back pain. IVDD is characterized by abnormal expression of extracellular matrix components such as collagen and aggrecan. In addition, it results in dysfunctional growth, senescence, and death of intervertebral cells. The biological pathways involved in the development and progress...

Cancer expands clonally, capitalizing on the variations between growing cells. Cancer cells specialize in one or more functions to gain an advantage. This study examined the prediction that cells would be vulnerable to drugs that perturb their specific tasks. We analyzed the correlation between gene expression and the response to drug perturbations...

Researchers use ChIP binding data to identify potential transcription factor binding sites. Similarly, they use gene expression data from sequencing or microarrays to quantify the effect of the transcription factor overexpression or knockdown on its targets. Therefore, the integration of the binding and expression data can be used to improve the un...

Breast cancer is the most prevalent type of cancer among women, and the vast majority of deaths are due to metastasis. Effective cancer therapies require an understanding of the underlying mechanisms and regulatory pathways of genes involved in metastasis. We applied text mining and a manual literature search to extract known interactions between s...

Screening for potential cancer therapies using existing large datasets of drug perturbations requires expertise and resources not available to all. This is often a barrier for lab scientists to tap into these valuable resources. To address these issues, one can take advantage of prior knowledge especially those coded in standard formats such as cau...

Backgound Autophagy controls levels of cellular components during normal and stress conditions; thus, it is a pivotal process for the maintenance of cell homeostasis. In cancer, autophagy protects cells from cancerous transformations that can result from genomic instability induced by reactive oxygen species or other damaged components, but it can...

Drug screening strategies focus on quantifying the phenotypic effects of different compounds on biological systems. High-throughput technologies have the potential to understand further the mechanisms by which these drugs produce the desired outcome. Reverse causal reasoning integrates existing biological knowledge and measurements of gene and prot...

Researchers use ChIP binding data to identify potential transcription factor binding sites. Similarly, they use gene expression data from sequencing or microarrays to quantify the effect of the transcription factor overexpression or knockdown on its targets. Therefore, the integration of the binding and expression data can be used to improve the un...

Researchers use ChIP binding data to identify potential transcription factor binding sites. Similarly, they use gene expression data from sequencing or microarrays to quantify the effect of the factor overexpression or knockdown on its targets. Therefore, the integration of the binding and expression data can be used to improve the understanding of...

Objectives • Integrate gene expression of cancer cell lines under drug perturbations and causal biological networks data • Evaluate the effect of drug treatments on perturbing the biological networks • Build a database and an interactive interface to make the output of the analysis accessible to all Summary Background. Screening for potential cance...

Aims: The development of osteoarthritis (OA), the most common form of arthritis, is commonly associated with oxidative stress. Indeed, the lack of antioxidant responses largely increases OA incidence. OA is a leading cause of disability in the elderly, which reduces the quality of life and places high socioeconomic burdens on them. Several polyphe...

Chromatin segmentation analysis transforms ChIP-seq data into signals over the genome. The latter represents the observed states in a multivariate Markov model to predict the chromatin's underlying states ChromHMM, written in Java, integrates histone modification datasets to learn the chromatin states de-novo. The goal of this package is to call ch...

Chromatin segmentation analysis transforms ChIP-seq data into signals over the genome. The latter represents the observed states in a multivariate Markov model to predict the chromatin’s underlying (hidden) states. ChromHMM, written in Java, integrates histone modification datasets to learn the chromatin states de-novo. We developed an R package ar...

Chromatin segmentation analysis transforms ChIP-seq data into signals over the genome. The latter represents the observed states in a multivariate Markov model to predict the chromatin's underlying (hidden) states. ChromHMM, written in Java, integrates histone modification datasets to learn the chromatin states de-novo. We developed an R package ar...

We previously showed that some adipogenic transcription factors such as CEBPB and PPARG, directly and indirectly, regulate autophagy gene expression in adipogenesis. The order and the effect of these events are undetermined. In this study, we modeled the gene expression, DNA-binding of transcriptional regulators, and histone modifications during ad...

Approach. We modeled the gene expression, DNA-binding of transcriptional regulators, and histone modifications during adipocyte differentiation [1, preprint available]. We evaluated the effect of the binding of the regulators on gene expression in terms of direction and magnitude. Then, we identified the overlap of the transcription factors and co-...

Raf kinase inhibitory protein (RKIP), also known as a phosphatidylethanolamine-binding protein 1 (PEBP1), functions as a tumor suppressor and regulates several signaling pathways, in- cluding ERK and NF-κB. RKIP is severely downregulated in human malignant cancers, indicating a functional association with cancer metastasis and poor prognosis. The t...

Researchers use ChIP binding data to identify potential transcription factor binding sites. Similarly, they use gene expression data from sequencing or microarrays to quantify the effect of the factor overexpression or knockdown on its targets. Therefore, the integration of the binding and expression data can be used to improve the understanding of...

Researchers use ChIP binding data to identify potential transcription factor binding sites. Similarly, they use gene expression data from sequencing or microarrays to quantify the effect of the factor overexpression or knockdown on its targets. Therefore, the integration of the binding and expression data can be used to improve the understanding of...

Autophagy is a highly conserved metabolic process involved in the degradation of intracellular components including proteins and organelles. Consequently, it plays a critical role in recycling metabolic energy for the maintenance of cellular homeostasis in response to various stressors. In cancer, autophagy either suppresses or promotes cancer prog...

Raf kinase inhibitory protein (RKIP), also known as a phosphatidylethanolamine-binding protein 1 (PEBP1), functions as a tumor suppressor and regulates several signaling pathways, including ERK and NF-κB. RKIP is severely downregulated in human malignant cancers, indicating a functional association with cancer metastasis and poor prognosis. The tra...

Differentiating 3T3-L1 pre-adipocytes are a mixture of non-identical culture cells. It is vital to identify the cell types that respond to the induction stimulus to understand the pre-adipocyte potential and the mature adipocyte behavior. To test this hypothesis, we deconvoluted the gene expression profiles of the cell culture of MDI-induced 3T3-L1...

Researchers use ChIP binding data to identify potential transcription factor binding sites. They use gene expression data from sequencing or microarrays to quantify the effect of the factor over-expression or knockdown on its targets. The integration of the binding and expression data therefore can be used to improve the understanding of a transcri...

Autophagy contributes to the development of various cell types, including adipocytes. During adipogenesis, autophagy takes part in the remodeling of the cell and provides the required energy. Here, I studied the role of adipogenic transcription factors in regulating autophagy gene products. First, I collected and curated a large dataset from previo...

We previously showed that some adipogenic transcription factors such as CEBPB and PPARG directly and indirectly regulate autophagy gene expression in adipogenesis. The order and the effect of these events are undetermined. In this study, we modeled the gene expression, DNA-binding of transcriptional regulators, and histone modifications during adip...

Researchers use ChIP binding data to identify potential transcription factor binding sites. They use gene expression data from sequencing or microarrays to quantify the effect of the factor over-expression or knockdown on its targets. The integration of the binding and expression data therefore can be used to improve the understanding of a transcri...

The 3T3-L1 cell line is used as an adipocyte differentiation model for the analysis of genes specifically expressed during the differentiation course. This cell model has several applications in obesity and insulin resistance research. We built a data resource to model gene expression of differentiating and mature adipocytes in response to several...

Background The binding of transcription factors to the gene regulatory regions induces or represses its expression. Co-factors and/or other DNA-binding proteins share the binding sites with transcription factors. These binding events do not always lead to a functional interaction. Results We developed a method to predict the combined functions of t...

Implement the BETA algorithm for inferring direct target genes from DNA-binding and perturbation expression data Wang et al. (2013). Extend the algorithm to predict the combined function of two DNA-binding elements from comparable binding and expression data.

Calculates the amplification efficiency and curves from real-time quantitative PCR (Polymerase Chain Reaction) data. Estimates the relative expression from PCR data using the double delta CT and the standard curve methods Livak & Schmittgen (2001) <doi:10.1006/meth.2001.1262>. Tests for statistical significance using two-group tests and linear regr...

A curated dataset of Microarrays samples. The samples are MDI- induced pre-adipocytes (3T3-L1) at different time points/stages of differentiation under different types of genetic (knockdown/overexpression) and pharmacological (drug treatment) perturbations. The package documents the data collection and processing. In addition to the documentation,...

The 3T3-L1 pre-adipocyte cell line is widely used to study the fat cell differentiation in vitro. Researchers also use this cell model to study obesity and insulin resistance. We surveyed the literature, the gene expression omnibus and the sequence read archive for RNA-Seq and ChIP-Seq datasets of MDI-induced 3T3-L1 differentiating cells sampled at...

Autophagy is the cell self-eating mechanism to maintain cell homeostasis by removing damaged intracellular proteins or organelles. It has also been implicated in the development and differentiation of various cell types including the adipocyte. Several links between adipogenic transcription factors and key autophagy genes has been suggested. In thi...

Background Autophagy has been implicated in the development and differentiation of various cell types including the adipocyte [3, 5]. The 3T3-L1 mouse fibroblast is a key model for studying the adipocyte differentiation. When the pre-adipocyte is induced with a chemical cocktail containing MDI (1-Methyl-3-isobutylxanthine, Dexametha-sone and Insuli...

One million females are diagnosed worldwide every year with breast cancer, and the mortality rate of these patients remains high. Several treatments, including surgery, are available for breast cancer. β‑Lapachone (β‑Lap), a natural quinone compound, has been developed for cancer treatment due to its strong cytotoxic effect through its action on NA...

Background. The co-localization analysis of fluorescence microscopy images is a widely used technique in biological research. It is often used to determine the co-distribution of two proteins inside the cell, suggesting that these two proteins could be functionally or physically associated. The limiting step in conducting microscopy image analysis...

Background: The co-localization analysis of fluorescence microscopy images is a widely used technique in biological research. It is often used to determine the co-distribution of two proteins inside the cell, suggesting that these two proteins could be functionally or physically associated. The limiting step in conducting microscopy image analysis...

The process of autophagy can be induced by extra-cellular and intracellular stimuli. Several studies suggested a role of oxidative stressors in relying the signals. The list of the interactions between the two pathways is growing. In this study, we identified the gene products of autophagy and oxidative stress using the corresponding gene ontology...

Automate the co-localization analysis of fluorescence microscopy images. Select regions of interest, extract pixel intensities from the image channels and calculate different co-localization statistics. The methods implemented in this package are based on Dunn et al. (2011) <doi:10.1152/ajpcell.00462.2010>.

Provide a set of functions to interact with the STRING API in R. The functions are organized around the API database and request types. The query parameters are checked and the output is returned in a tibble.

A curated dataset of RNA-Seq samples. The samples are MDI-induced pre-phagocytes (3T3-L1) at different time points/stages of differentiation. The package document the data collection, pre-processing, and processing. In addition to the documentation, the package contains the scripts that were used to generate the data.

A curated dataset of publicly available ChIP-sequencing of transcription factors, chromatin remodelers, and histone modifications in the 3T3-L1 pre-adipocyte cell line. The package document the data collection, pre-processing, and processing of the data. In addition to the documentation, the package contains the scripts that were used to generate t...

Background The co-localization analysis of fluorescence microscopy images is a widely used technique in biological research. It is often used to determine the co-distribution of two proteins inside the cell, suggesting that these two proteins could be functionally or physically associated. The limiting step in conducting microscopy image analysis i...

Background Transcription factors and microRNAs play a critical role in regulating the gene expression in normal physiology and pathological conditions. Many bioinformatics tools were built to predict and identify transcription factor and microRNA targets and their role in the development of diseases including cancers. The availability of public acc...

Autophagy, an intracellular degradation process, is essential for maintaining cell homeostasis by removing damaged organelles and proteins under various conditions of stress. In cancer, autophagy has conflicting functions. It plays a key role in protecting against cancerous transformation by maintaining genomic stability against genotoxic component...

Oxidative damage in neurons including glutamate excitotoxicity has been linked to increasing numbers of neuropathological conditions. Under these conditions, cells trigger several different cellular responses such as autophagy, apoptosis, necrosis and senescence. However, the connection between these responses is not well understood. In this study,...

Raf kinase inhibitor protein (RKIP) functions as an anti-cancer protein in certain types of cancer cells, so loss of function results in the promotion of cancer progression. RKIP also inhibits autophagy by modulating LC3-lipidation and mTORC1. Other ways of RKIP-dependent inhibition of autophagy specifically during cancer progression are still unde...

Builds a 'SQLite' database file of pre-calculated transcription factor/microRNA-gene correlations (co-expression) in cancer from the Cistrome Cancer Liu et al. (2011) <doi:10.1186/gb-2011-12-8-r83> and 'miRCancerdb' databases (in press). Provides custom classes and functions to query, tidy and plot the correlation data.

Objectives: microRNAs regulate expression of target genes by specifically binding to their transcripts, subsequently leading to translational inhibition or mRNA degradation. Gene regulation by microRNAs has been implicated in a wide range of physiological and pathological conditions. Here, we leverage the use of public-access data and the availabl...

Background Raf kinase inhibitor protein (RKIP) plays a critical role in many signaling pathways as a multi-functional adapter protein. In particular, the loss of RKIP's function in certain types of cancer cells results in ep-ithelial to mesenchymal transition (EMT) and the promotion of cancer metastasis. Also, RKIP inhibits autophagy by modulating...

Raf kinase inhibitor protein (RKIP) plays a critical role in many signaling pathways as a multi-functional adapter protein. In particular, the loss of RKIP’s function in certain types of cancer cells results in epithelial to mesenchymal transition (EMT) and the promotion of cancer metastasis. In addition, RKIP inhibits autophagy by modulating LC3-l...