Showing papers in "Briefings in Functional Genomics in 2013"
TL;DR: From the cataloguing of the in vivo genomic targets of STAT3 (the transcription factor downstream of IL-10) to the identification of specific co-factors that endow STAT3 with genomic-binding specificity, and how genomic and computational methods are being used to elucidate the regulatory mechanisms of this essential physiological response in macrophages are reviewed.
Abstract: Inflammation is a fundamental response of the immune system whose successful termination involves the elimination of the invading pathogens, the resolution of inflammation and the repair of the local damaged tissue. In this context, the interleukin 10 (IL-10)-mediated anti-inflammatory response (AIR) represents an essential homeostatic mechanism that controls the degree and duration of inflammation. Here, we review recent work on the mechanistic characterization of the IL-10-mediated AIR on multiple levels: from the cataloguing of the in vivo genomic targets of STAT3 (the transcription factor downstream of IL-10) to the identification of specific co-factors that endow STAT3 with genomic-binding specificity, and how genomic and computational methods are being used to elucidate the regulatory mechanisms of this essential physiological response in macrophages.
295 citations
TL;DR: This review summarizes the mechanisms by which RBPs regulate mRNA translation, with special focus on those binding to the 3′-untranslated region and how recent high-throughput technologies are revealing exquisite layers of complexity.
Abstract: The regulation of mRNA translation is a major checkpoint in the flux of information from the transcriptome to the proteome. Critical for translational control are the trans-acting factors, RNA-binding proteins (RBPs) and small RNAs that bind to the mRNA and modify its translatability. This review summarizes the mechanisms by which RBPs regulate mRNA translation, with special focus on those binding to the 3'-untranslated region. It also discusses how recent high-throughput technologies are revealing exquisite layers of complexity and are helping to untangle translational regulation at a genome-wide scale.
164 citations
TL;DR: With the use of histone deacetylase inhibitors and acetylation modulators (e.g. HAT inhibitors, bromodomain inhibitors), this work is paving the way for a future epigenetic drug control of human diseases.
Abstract: Lysine N-e-acetylation is a post-translational modification that regulates the function of histone and non-histone proteins. In several malignancies, histone acetyltransferase (HAT) activities are disturbed as a consequence of various genetic or epigenetic alterations. In particular, HATs can function as tumor suppressors, helping cells control cellular proliferation and cell cycle, and also as oncogenes, because abnormal acetylation can activate malignant proteins and contribute to cancer. An impaired acetylation profile can be indicative of a pathological process, and thus evaluation of histone acetylation could be used as a predictive index of patient survival or therapy outcome. Therefore, epigenetic therapy might be a very effective strategy to defeat cancer. With the use of histone deacetylase inhibitors and acetylation modulators (e.g. HAT inhibitors, bromodomain inhibitors), we are paving the way for a future epigenetic drug control of human diseases.
122 citations
TL;DR: Current understanding of cancer methylomes indicates that most affected CGI genes are already silenced prior to aberrant hypermethylation during cancer development, and how genome-scale analyses of both normal and cancer cells have refined the understanding of the elusive mechanism(s) that may underpin aberrant CGIhypermethylation.
Abstract: Carcinogenesis is thought to occur through a combination of mutational and epimutational events that disrupt key pathways regulating cellular growth and division. The DNA methylomes of cancer cells can exhibit two striking differences from normal cells; a global reduction of DNA methylation levels and the aberrant hypermethylation of some sequences, particularly CpG islands (CGIs). This aberrant hypermethylation is often invoked as a mechanism causing the transcriptional inactivation of tumour suppressor genes that directly drives the carcinogenic process. Here, we review our current understanding of this phenomenon, focusing on how global analysis of cancer methylomes indicates that most affected CGI genes are already silenced prior to aberrant hypermethylation during cancer development. We also discuss how genome-scale analyses of both normal and cancer cells have refined our understanding of the elusive mechanism(s) that may underpin aberrant CGI hypermethylation.
115 citations
TL;DR: The association between specific taxa and obesity, together with the techniques that are used to characterize the gut microbiota in the context of obesity and type 2 diabetes, are discussed.
Abstract: The distal gut harbours microbial communities that outnumber our own eukaryotic cells. The contribution of the gut microbiota to the development of several diseases (e.g. obesity, type 2 diabetes, steatosis, cardiovascular diseases and inflammatory bowel diseases) is becoming clear, although the causality remains to be proven in humans. Global changes in the gut microbiota have been observed by a number of culture-dependent and culture-independent methods, and while the latter have mostly included 16S ribosomal RNA gene analyses, more recent studies have utilized DNA sequencing of whole-microbial communities. Altogether, these high-throughput methods have facilitated the identification of novel candidate bacteria and, most importantly, metabolic functions that might be associated with obesity and type 2 diabetes. This review discusses the association between specific taxa and obesity, together with the techniques that are used to characterize the gut microbiota in the context of obesity and type 2 diabetes. Recent results are discussed in the framework of the interactions between gut microbiota and host metabolism.
107 citations
TL;DR: The growing evidence that ncRNAs are intrinsically involved in cellular and organismal adaptation processes, in both robustness and protection to stresses, as well as in mechanisms generating evolutionary change is presented.
Abstract: Cells and organisms are subject to challenges and perturbations in their environment and physiology in all stages of life. The molecular response to such changes, including insulting conditions such as pathogen infections, involves coordinated modulation of gene expression programmes and has not only homeostatic but also ecological and evolutionary importance. Although attention has been primarily focused on signalling pathways and protein networks, non–coding RNAs (ncRNAs), which comprise a significant output of the genomes of prokaryotes and especially eukaryotes, are increasingly implicated in the molecular mechanisms of these responses. Long and short ncRNAs not only regulate development and cell physiology, they are also involved in disease states, including cancers, in host–pathogen interactions, and in a variety of stress responses. Indeed, regulatory RNAs are part of genetically encoded response networks and also underpin epigenetic processes, which are emerging as key mechanisms of adaptation and transgenerational inheritance. Here we present the growing evidence that ncRNAs are intrinsically involved in cellular and organismal adaptation processes, in both robustness and protection to stresses, as well as in mechanisms generating evolutionary change.
93 citations
TL;DR: An overview of the different forms of transcription factor interplay that have been identified and how T cell phenotypes arise as a product of this interplay within complex regulatory networks is presented and suggest experimental strategies that will provide further insight into the mechanisms that underlie T cell lineage specification and plasticity.
Abstract: The differentiation of CD4 helper T cells into specialized effector lineages has provided a powerful model for understanding immune cell differentiation. Distinct lineages have been defined by differential expression of signature cytokines and the lineage-specifying transcription factors necessary and sufficient for their production. The traditional paradigm of differentiation towards Th1 and Th2 subtypes driven by T-bet and GATA3, respectively, has been extended to incorporate additional T cell lineages and transcriptional regulators. Technological advances have expanded our view of these lineage-specifying transcription factors to the whole genome and revealed unexpected interplay between them. From these data, it is becoming clear that lineage specification is more complex and plastic than previous models might have suggested. Here, we present an overview of the different forms of transcription factor interplay that have been identified and how T cell phenotypes arise as a product of this interplay within complex regulatory networks. We also suggest experimental strategies that will provide further insight into the mechanisms that underlie T cell lineage specification and plasticity.
79 citations
TL;DR: Small molecules with high specificity for the Bromodomain and Extra Terminal family of proteins (BRD2,BRD3, BRD4 and BRDT) have recently been shown to have remarkable pre-clinical efficacy in various malignancies and provided the impetus for exploring other BRD proteins as novel targets in cancer therapy.
Abstract: The malleability of the epigenome has long been recognized as a unique opportunity for therapeutic intervention. Interest in targeting components of the epigenetic machinery for therapeutic gain had initially been aimed at chromatin modifying enzymes. However, advances in medicinal chemistry have now made it possible to exploit protein-protein interactions at the chromatin interface. Bromodomains (BRD) are a conserved motif used by a large number of chromatin-associated proteins to recognize and bind acetylated histone tails. Small molecules with high specificity for the Bromodomain and Extra Terminal family of proteins (BRD2, BRD3, BRD4 and BRDT) have recently been shown to have remarkable pre-clinical efficacy in various malignancies. These findings have provided the impetus for exploring other BRD proteins as novel targets in cancer therapy.
69 citations
TL;DR: Diverse aspects of precursor processing in plants are summarized, contrasting them to their animal counterparts.
Abstract: MicroRNAs are endogenous small RNAs known to be key regulators of gene expression in animals and plants. They are defined by their specific biogenesis which involves the precise excision from an imperfect fold-back precursor. These precursors contain structural determinants required for their correct processing. Still, there are significant differences in the biogenesis and activities of plant and animal microRNAs. This review summarizes diverse aspects of precursor processing in plants, contrasting them to their animal counterparts.
66 citations
TL;DR: These findings questioned the paradigm of virulence by gene acquisition and put forward the notion of genomic repertoire ofvirulence, which is a new era of pathogen research.
Abstract: In the pregenomic era, the acquisition of pathogenicity islands via horizontal transfer was proposed as a major mechanism in pathogen evolution. Much effort has been expended to look for the contiguous blocks of virulence genes that are present in pathogenic bacteria, but absent in closely related species that are nonpathogenic. However, some of these virulence factors were found in nonpathogenic bacteria. Moreover, and contrary to expectation, pathogenic bacteria were found to lack genes (antivirulence genes) that are characteristic of nonpathogenic bacteria. The availability of complete genome sequences has led to a new era of pathogen research. Comparisons of genomes have shown that the most pathogenic bacteria have reduced genomes, with less ribosomal RNA and unorganized operons; they lack transcriptional regulators but have more genes that encode protein toxins, toxin-antitoxin (TA) modules, and proteins for DNA replication and repair, when compared with less pathogenic close relatives. These findings questioned the paradigm of virulence by gene acquisition and put forward the notion of genomic repertoire of virulence.
65 citations
TL;DR: With the commercialization of a third generation of sequencing technologies imminent, this work discusses the applications of current next-generation sequencing methods and explores their impact on and contribution to microbial genome research.
Abstract: Next-generation sequencing technologies have had a dramatic impact in the field of genomic research through the provision of a low cost, high-throughput alternative to traditional capillary sequencers. These new sequencing methods have surpassed their original scope and now provide a range of utility-based applications, which allow for a more comprehensive analysis of the structure and content of microbial genomes than was previously possible. With the commercialization of a third generation of sequencing technologies imminent, we discuss the applications of current next-generation sequencing methods and explore their impact on and contribution to microbial genome research.
TL;DR: It is argued that mitochondrial- and chloroplast-derived sequences are an excellent and untapped resource for investigating many aspects of organelle function and evolution.
Abstract: GenBank is bursting with eukaryotic RNA sequencing (RNA-Seq) results. These data are transforming our view of nuclear transcriptional architecture, but many scientists are ignoring a major component of the data: mitochondrial- and chloroplast-derived sequences. Indeed, organelle transcripts typically represent a significant proportion of the reads generated from eukaryotic RNA-Seq experiments. Here, I argue that these data are an excellent and untapped resource for investigating many aspects of organelle function and evolution.
TL;DR: The methodologies for association described herein can be applied to other data types, opening up possibilities to analyze transcriptome–phenotype associations, and correlate microbial population structure or activity, as measured by metagenomics, to environmental parameters.
Abstract: There is an increasing availability of complete or draft genome sequences for microbial organisms. These data form a potentially valuable resource for genotype-phenotype association and gene function prediction, provided that phenotypes are consistently annotated for all the sequenced strains. In this review, we address the requirements for successful gene-trait matching. We outline a basic protocol for microbial functional genomics, including genome assembly, annotation of genotypes (including single nucleotide polymorphisms, orthologous groups and prophages), data pre-processing, genotype-phenotype association, visualization and interpretation of results. The methodologies for association described herein can be applied to other data types, opening up possibilities to analyze transcriptome-phenotype associations, and correlate microbial population structure or activity, as measured by metagenomics, to environmental parameters.
TL;DR: Recent methodologies used for plant gene expression data are reviewed and the results, advantages and disadvantages are compared in order to help researchers in their choice of a method for the construction of GCNs.
Abstract: Techniques in molecular biology have permitted the gathering of an extremely large amount of information relating organisms and their genes. The current challenge is assigning a putative function to thousands of genes that have been detected in different organisms. One of the most informative types of genomic data to achieve a better knowledge of protein function is gene expression data. Based on gene expression data and assuming that genes involved in the same function should have a similar or correlated expression pattern, a function can be attributed to those genes with unknown functions when they appear to be linked in a gene co-expression network (GCN). Several tools for the construction of GCNs have been proposed and applied to plant gene expression data. Here, we review recent methodologies used for plant gene expression data and compare the results, advantages and disadvantages in order to help researchers in their choice of a method for the construction of GCNs.
TL;DR: This article will introduce epigenetic memory and the mechanisms by which it may operate in the context of nuclear reprogramming, and briefly discuss the relevance of memory and reprograming to cancer biology.
Abstract: Epigenetic memory represents a natural mechanism whereby the identity of a cell is maintained through successive cell cycles, allowing the specification and maintenance of differentiation during development and in adult cells. Cancer is a loss or reversal of the stable differentiated state of adult cells and may be mediated in part by epigenetic changes. The identity of somatic cells can also be reversed experimentally by nuclear reprogramming. Nuclear reprogramming experiments reveal the mechanisms required to activate embryonic gene expression in adult cells and thus provide insight into the reversal of epigenetic memory. In this article, we will introduce epigenetic memory and the mechanisms by which it may operate. We limit our discussion primarily to the context of nuclear reprogramming and briefly discuss the relevance of memory and reprogramming to cancer biology.
TL;DR: The TET enzymes as epigenetic DNA modifiers, their physiological roles, and their functions in health and disease are highlighted, and the need to find relevant TET interactants and the newly discovered N-acetylglucosamine transferase (OGT) pathway is discussed.
Abstract: Epigenetic genome marking and chromatin regulation are central to establishing tissue-specific gene expression programs, and hence to several biological processes. Until recently, the only known epigenetic mark on DNA in mammals was 5-methylcytosine, established and propagated by DNA methyltransferases and generally associated with gene repression. All of a sudden, a host of new actors-novel cytosine modifications and the ten eleven translocation (TET) enzymes-has appeared on the scene, sparking great interest. The challenge is now to uncover the roles they play and how they relate to DNA demethylation. Knowledge is accumulating at a frantic pace, linking these new players to essential biological processes (e.g. cell pluripotency and development) and also to cancerogenesis. Here, we review the recent progress in this exciting field, highlighting the TET enzymes as epigenetic DNA modifiers, their physiological roles, and their functions in health and disease. We also discuss the need to find relevant TET interactants and the newly discovered TET-O-linked N-acetylglucosamine transferase (OGT) pathway.
TL;DR: NMD controls the levels of physiologic transcripts, which defines this pathway as a novel gene expression regulator, with huge impact on homeostasis, cell growth and development and links between NMD and cell growth, animal development and diseases.
Abstract: Cells are able to recognize and degrade aberrant transcripts in order to self-protect from potentially toxic proteins. Various pathways detect aberrant RNAs in the cytoplasm and are dependent on translation. One of these pathways is the nonsense-mediated RNA decay (NMD). NMD is a surveillance mechanism that degrades transcripts containing nonsense mutations, preventing the translation of possibly harmful truncated proteins. For example, the degradation of a nonsense harming β-globin allele renders normal phenotypes. On the other hand, regulating NMD is also important in those cases when the produced aberrant protein is better than having no protein, as it has been shown for cystic fibrosis. These findings reflect the important role for NMD in human health. In addition, NMD controls the levels of physiologic transcripts, which defines this pathway as a novel gene expression regulator, with huge impact on homeostasis, cell growth and development. While the mechanistic details of NMD are being gradually understood, the physiological role of this RNA surveillance pathway still remains largely unknown. This is a brief and simplified review on various aspects of NMD, such as the nature of the NMD targets, the mechanism of target degradation and the links between NMD and cell growth, animal development and diseases.
TL;DR: This review discusses how these mRNAs are concurrently regulated at the post-transcriptional level by microRNAs (miRNAs) and RNA-binding proteins (RBPs), which consequently modify the p53 transcriptional program in a cell type- and stimulus-specific manner.
Abstract: The p53 transcription factor regulates the synthesis of mRNAs encoding proteins involved in diverse cellular stress responses such as cell-cycle arrest, apoptosis, autophagy and senescence. In this review, we discuss how these mRNAs are concurrently regulated at the post-transcriptional level by microRNAs (miRNAs) and RNA-binding proteins (RBPs), which consequently modify the p53 transcriptional program in a cell type- and stimulus-specific manner. We also discuss the action of specific miRNAs and RBPs that are direct transcriptional targets of p53 and how they act coordinately with protein-coding p53 target genes to orchestrate p53-dependent cellular responses.
TL;DR: The statistical relations between the timing of different events may reveal how their respective processes are related biologically: Do they occur in sequence or in parallel?
Abstract: The timing of a cellular event often hides critical information on the process leading to the event. Our ability to measure event times in single cells along with other quantities allow us to learn about the drivers of the timed process and its downstream effects. In this review, we cover different types of events that have been timed in single cells, methods to time such events and types of analysis that have been applied to event timings. We show how different timing distributions suggest different natures for the process. The statistical relations between the timing of different events may reveal how their respective processes are related biologically: Do they occur in sequence or in parallel? Are they independent or inter-dependent? Finally, quantifying morphological and molecular variables may help assess their contribution to the timing of an event and its related process.
TL;DR: Novel biomarkers are strongly needed to enable more accurate detection of PCa, improve prediction of tumor aggressiveness and facilitate the discovery of new therapeutic targets for tailored medicine.
Abstract: Prostate cancer (PCa) is the second most commonly diagnosed malignancy in men in the Western world and the second leading cause of cancer-related deaths among men worldwide. Although most cancers have the potential to metastasize under appropriate conditions, PCa favors the skeleton as a primary site of metastasis, suggesting that the bone microenvironment is conducive to its growth. PCa metastasis proceeds through a complex series of molecular events that include angiogenesis at the site of the original tumor, local migration within the primary site, intravasation into the blood stream, survival within the circulation, extravasation of the tumor cells to the target organ and colonization of those cells within the new site. In turn, each one of these steps involves a complicated chain of events that utilize multiple protein ^ protein interactions, protein signaling cascades and transcriptional changes. Despite the urgent need to improve current biomarkers for diagnosis, prognosis and drug resistance, advances have been slow. Global gene expression methods such as gene microarrays and RNA sequencing enable the study of thousands of genes simultaneously and allow scientists to examine molecular pathways of cancer pathogenesis. In this review, we summarize the current literature that explored high-throughput transcriptome analysis toward the advancement of biomarker discovery for PCa. Novel biomarkers are strongly needed to enable more accurate detection of PCa, improve prediction of tumor aggressiveness and facilitate the discovery of new therapeutic targets for tailored medicine. Promising molecular markers identified from gene expression profiling studies include HPN, CLU1, WT1, WNT5A, AURKA and SPARC.
TL;DR: An overview of the applications of MS-based proteomics in studying various aspects of chromatin biology is given and how novel proteomic approaches are being utilized to identify and study chromatin-associated proteins and multi-subunit complexes are discussed.
Abstract: The involvement of epigenetic processes in the origin and progression of cancer is now widely appreciated. Consequently, targeting the enzymatic machinery that controls the epigenetic regulation of the genome has emerged as an attractive new strategy for therapeutic intervention. The development of epigenetic drugs requires a detailed knowledge of the processes that govern chromatin regulation. Over the recent years, mass spectrometry (MS) has become an indispensable tool in epigenetics research. In this review, we will give an overview of the applications of MS-based proteomics in studying various aspects of chromatin biology. We will focus on the use of MS in the discovery and mapping of histone modifications and how novel proteomic approaches are being utilized to identify and study chromatin-associated proteins and multi-subunit complexes. Finally, we will discuss the application of proteomic methods in the diagnosis and prognosis of cancer based on epigenetic biomarkers and comment on their future impact on cancer epigenetics.
TL;DR: Calculations suggest that by combining super-resolution microscopy and barcode labeling, single cells can be turned into informatics platforms denser than microarrays and that molecular species in individual Cells can be profiled in a massively parallel fashion.
Abstract: In this review, we discuss a strategy to bring genomics and proteomics into single cells by super-resolution microscopy. The basis for this new approach are the following: given the 10 nm resolution of a super-resolution microscope and a typical cell with a size of (10 µm)^3, individual cells contain effectively 10^9 super-resolution pixels or bits of information. Most eukaryotic cells have 10^4 genes and cellular abundances of 10–100 copies per transcript. Thus, under a super-resolution microscope, an individual cell has 1000 times more pixel volume or information capacities than is needed to encode all transcripts within that cell. Individual species of mRNA can be uniquely identified by labeling them each with a distinct combination of fluorophores by fluorescence in situ hybridization. With at least 15 fluorophores available in super-resolution, hundreds of genes in can be barcoded with a three-color barcode (_3C_(15) = 455). These calculations suggest that by combining super-resolution microscopy and barcode labeling, single cells can be turned into informatics platforms denser than microarrays and that molecular species in individual cells can be profiled in a massively parallel fashion.
TL;DR: The potential of single-cell gene expression profiling is discussed, focusing on data analysis and biological interpretation, and several aspects of the added value ofsingle-cell analysis are exemplified by comparing the same experimental data at both single- cell and cell population level.
Abstract: Cells are the basic unit of life and they have remarkable abilities to respond individually as well as in concert to internal and external stimuli in a specific manner. Studying complex tissues and whole organs requires understanding of cell heterogeneity and responses to stimuli at the single-cell level. In this review, we discuss the potential of single-cell gene expression profiling, focusing on data analysis and biological interpretation. We exemplify several aspects of the added value of single-cell analysis by comparing the same experimental data at both single-cell and cell population level. Data normalization and handling of missing data are two important steps in data analysis that are performed differently at single-cell level compared with cell population level. Furthermore, we discuss how single-cell gene expression data can be viewed and how subpopulations of cells can be identified and characterized.
TL;DR: The definition of 'functional genomics' encompasses a range of aspects: phage genome sequencing, annotation and ascribing functions to phage genes, prophage identification in bacterial sequences, elucidating the events in various stages of phage life cycle using genomic, transcriptomic and proteomic approaches, defining the mechanisms of host takeover including specific bacterial-phage protein interactions and identifying virulence and other adaptive features encoded by phages.
Abstract: Emerging and reemerging bacterial infectious diseases are a major public health concern worldwide. The role of bacteriophages in the emergence of novel bacterial pathogens by horizontal gene transfer was highlighted by the May 2011 Escherichia coli O104:H4 outbreaks that originated in Germany and spread to other European countries. This outbreak also highlighted the pivotal role played by recent advances in functional genomics in rapidly deciphering the virulence mechanism elicited by this novel pathogen and developing rapid diagnostics and therapeutics. However, despite a steady increase in the number of phage sequences in the public databases, boosted by the next-generation sequencing technologies, few functional genomics studies of bacteriophages have been conducted. Our definition of 'functional genomics' encompasses a range of aspects: phage genome sequencing, annotation and ascribing functions to phage genes, prophage identification in bacterial sequences, elucidating the events in various stages of phage life cycle using genomic, transcriptomic and proteomic approaches, defining the mechanisms of host takeover including specific bacterial-phage protein interactions and identifying virulence and other adaptive features encoded by phages and finally, using prophage genomic information for bacterial detection/diagnostics. Given the breadth and depth of this definition and the fact that some of these aspects (especially phage-encoded virulence/adaptive features) have been treated extensively in other reviews, we restrict our focus only on certain aspects. These include phage genome sequencing and annotation, identification of prophages in bacterial sequences and genetic characterization of phages, functional genomics of the infection process and finally, bacterial identification using genomic information.
TL;DR: Key discoveries are highlighted where live-cell imaging has provided unprecedented insights into how cells respond to DNA double-strand breaks and the main challenges and promises in using this technique are discussed.
Abstract: All organisms have to safeguard the integrity of their genome to prevent malfunctioning and oncogenic transformation. Sophisticated DNA damage response mechanisms have evolved to detect and repair genomic lesions. With the emergence of live-cell microscopy of individual cells, we now begin to appreciate the complex spatiotemporal kinetics of the DNA damage response and can address the causes and consequences of the heterogeneity in the responses of genetically identical cells. Here, we highlight key discoveries where live-cell imaging has provided unprecedented insights into how cells respond to DNA double-strand breaks and discuss the main challenges and promises in using this technique.
TL;DR: This review will discuss the central role of methylation in the regulation of gene expression, its alterations in cancer as well as its possible targeting for cancer therapies.
Abstract: Cancer results from abnormal gene expression that transforms cellular identity. A rising consensus is that genetic mutations and epigenetic alterations act in concert to achieve tumorigenesis. On one hand, cancer cells harbor classic genetic mutations that activate oncogenes and inhibit tumor suppressors. On the other hand, they also display broad alterations of their epigenomes, as defined by modifications of DNA, histones and coding/noncoding RNAs. In particular, methylation is a ubiquitous modification that affects several residues/sites in these molecules. In this review, I will discuss the central role of this modification in the regulation of gene expression, its alterations in cancer as well as its possible targeting for cancer therapies.
TL;DR: An overview on metabolic modelling is provided, which has the capability to integrate information from functional genomics studies in P. falciparum and guide future malaria research efforts towards the identification of novel candidate drug targets.
Abstract: Plasmodium falciparum is an obligate intracellular parasite and the leading cause of severe malaria responsible for tremendous morbidity and mortality particularly in sub-Saharan Africa. Successful completion of the P. falciparum genome sequencing project in 2002 provided a comprehensive foundation for functional genomic studies on this pathogen in the following decade. Over this period, a large spectrum of experimental approaches has been deployed to improve and expand the scope of functionally annotated genes. Meanwhile, rapidly evolving methods of systems biology have also begun to contribute to a more global understanding of various aspects of the biology and pathogenesis of malaria. Herein we provide an overview on metabolic modelling, which has the capability to integrate information from functional genomics studies in P. falciparum and guide future malaria research efforts towards the identification of novel candidate drug targets.
TL;DR: How high-throughput genomic technologies have increased understanding about the molecular complexity of breast cancer, identified distinct molecular phenotypes and how they can be used to increase the accuracy of predicted clinical outcome is reviewed.
Abstract: Microarray technologies provide high-throughput analysis of genes that are differentially expressed in humans and other species, and thereby provide a means to measure how biological systems are altered during development or disease states. Within, we review how high-throughput genomic technologies have increased our understanding about the molecular complexity of breast cancer, identified distinct molecular phenotypes and how they can be used to increase the accuracy of predicted clinical outcome.
TL;DR: This review introduces the marine annelid Platynereis dumerilii, a member of the lophotrochozoan clade, as a suitable model system for the simultaneous study of macro-evolutionary processes across phyla and of micro-evolved processes across highly polymorphic populations collected worldwide.
Abstract: Ever since the origin of the first metazoans over 600 million years ago, cell type diversification has been driven by micro-evolutionary processes at population level, leading to macro-evolution changes above species level. In this review, we introduce the marine annelid Platynereis dumerilii, a member of the lophotrochozoan clade (a key yet most understudied superphylum of bilaterians), as a suitable model system for the simultaneous study, at cellular resolution, of macro-evolutionary processes across phyla and of micro-evolutionary processes across highly polymorphic populations collected worldwide. Recent advances in molecular and experimental techniques, easy maintenance and breeding, and the fast, synchronous and stereotypical development have facilitated the establishment of Platynereis as one of the leading model species in the eco-evo-devo field. Most importantly, Platynereis allows the combination of expression profiling, morphological and physiological characterization at the single cell level. Here, we discuss recent advances in the collection of -omics data for the lab strain and for natural populations collected world-wide that can be integrated with population-specific cellular analyses to result in a cellular atlas integrating genetic, phenotypic and ecological variation. This makes Platynereis a tractable system to begin understanding the interplay between macro- and micro-evolutionary processes and cell type diversity.
TL;DR: It is recapitulate that pseudogenes harbor disease-causing degenerative sequence variations in conjunction with the immense disease gene association of their progenitors.
Abstract: Pseudogenes, the nonfunctional homologs of functional genes and thus exemplified as 'genomic fossils' provide intriguing snapshots of the evolutionary history of human genome. These defunct copies generally arise by retrotransposition or duplication followed by various genetic disablements. In this study, focusing on human pseudogenes and their functional homologues we describe their characteristic features and relevance to protein sequence evolution. We recapitulate that pseudogenes harbor disease-causing degenerative sequence variations in conjunction with the immense disease gene association of their progenitors. Furthermore, we also discuss the issue of functional resurrection and the potentiality observed in some pseudogenes to regulate their functional counterparts.