http://www.biomedcentral.com/bmcgenomics/ The latest research articles published by BMC Genomics 2009-07-09T00:00:00Z This is an RSS newsfeed from BioMed Central It is intended to be used with an RSS reader. For more information about RSS newsfeeds from BioMed Central, visit http://www.biomedcentral.com/info/about/rss/ Background: Hormones are signaling molecules that play vital roles in various life processes, like growth and differentiation, physiology, and reproduction. These molecules are mostly secreted by endocrine glands, and transported to target organs through the bloodstream. Deficient, or excessive, levels of hormones are associated with several diseases such as cancer, osteoporosis, diabetes etc. Thus, it is important to collect and compile information about hormones and their receptors.DescriptionThis manuscript describes a database called Hmrbase which has been developed for managing information about hormones and their receptors. It is a highly curated database for which information has been collected from the literature and the public databases. The current version of Hmrbase contains comprehensive information about ~2000 hormones, e.g., about their function, source organism, receptors, mature sequences, structures etc. Hmrbase also contains information about ~3000 hormone receptors, in terms of amino acid sequences, subcellular localizations, ligands, and post-translational modifications etc. One of the major features of this database is that it provides data about ~4100 hormone-receptor pairs. A number of online tools have been integrated into the database, to provide the facilities like keyword search, structure-based search, mapping of a given peptide(s) on the hormone/receptor sequence, sequence similarity search. This database also provides a number of external links to other resources/databases in order to help in the retrieving of further related information. Conclusions: Owing to the high impact of endocrine research in the biomedical sciences, the Hmrbase could become a leading data portal for researchers. The salient features of Hmrbase are hormone-receptor pair-related information, mapping of peptide stretches on the protein sequences of hormones and receptors, Pfam domain annotations, categorical browsing options, online data submission, DrugPedia linkage etc. Hmrbase is available online for public from http://crdd.osdd.net/raghava/hmrbase/. http://www.biomedcentral.com/1471-2164/10/307 Mamoon Rashid Deepak Singla Arun Sharma Manish Kumar Gajendra Raghava BMC Genomics 2009, 10:307 2009-07-09T00:00:00Z doi:10.1186/1471-2164-10-307 BMC Genomics 1471-2164 10 307 2009-07-09T00:00:00Z PDF Background: The thermotolerance of Aspergillus fumigatus plays a critical role in mammalian and avian infections. Thus, the identification of its adaptation mechanism to higher temperature is very important for an efficient anti-fungal drug development as well as fundamental understanding of its pathogenesis. We explored the temporal transcription regulation structure of this pathogenic fungus under heat shock conditions using the time series microarray data reported by Nierman et al. (Nature 2005, 438:1151-1156). Results: The estimated transcription regulation structure of A. fumigatus shows that the heat shock proteins are strongly negatively associated with central metabolic pathway genes such as the tricarboxylic acid cycle (TCA cycle) and carbohydrate metabolism. It was 60 min and 120 min, respectively, after the growth temperature changes from 30 degreesC (corresponding to environments of tropical soil) to 37 degreesC and 48 degreesC (corresponding to temperatures in the human body and compost, respectively) that some of genes in TCA cycle were started to be upregulated. In these points, most of heat shock proteins showed lowest expression level after heat shocks. Among the heat shock proteins, the HSP30 (AFU6G06470), a single integral plasma membrane heat shock protein, presented most active role in transcription regulation structure in both heat shock conditions of 37 degreesC and 48 degreesC. The metabolic genes associated with multiple genes in the gene regulation network tended to have opposite expression patterns to that of heat shock protein AFU6G06470 and the these metabolic genes played a role to help the regulation of heat shock proteins. That is, the heat shock proteins and these metabolic genes showed the coherent regulation or the coherent feed-forward loop type of regulation towards target genes. This type of regulation structure might be very advantageous for the cells of A. fumigatus under heat shock because a small amount of heat shock proteins can rapidly magnify their regulation effect on target genes. However, this type of regulation was become weak with temperature. This might be the reason for dramatic increase in the expression of heat shock proteins and the number of heat shock response genes at heat shock of 48 degreesC. Conclusions: We systemically analysed the thermal adaption mechanism of A. fumigatus by state space model with times series microarray data in terms of transcription regulation structure. We suggest a transcription regulation structure or network during thermal adaptation process that heat shock proteins could efficiently regulate their target genes by the coherent regulation or the coherent feed-forward loop type of regulation with metabolic genes. This type of regulation structure would also be efficient cellular strategy for other stressful conditions requiring rapid metabolic response. http://www.biomedcentral.com/1471-2164/10/306 Jin Hwan Do Rui Yamaguchi Satoru Miyano BMC Genomics 2009, 10:306 2009-07-08T00:00:00Z doi:10.1186/1471-2164-10-306 BMC Genomics 1471-2164 10 306 2009-07-08T00:00:00Z PDF Background: Skeletal muscle growth and maintenance are essential for human health. One of the muscle regulatory genes, namely myostatin, a member of transforming growth factor-beta, plays a dominant role in the genetic control of muscle mass. Myostatin is synthesized as a precursor protein, which generates the N-terminal propeptide and the C-terminal mature myostatin peptide by a post-translational cleavage event. Previously, transgenic over-expression of myostatin propeptide in skeletal muscle results in significant muscle growth in early stages of development. The objectives of present study were to further characterize muscle growth in later stages of life and to identify genes and their expression patterns that are responsible for adult muscle build-up by myostatin propeptide. Results: Immunohistochemical staining with an antibody to the N-terminus indicates a high level of myostatin propeptide present in the muscles of transgenic mice while there were no apparent differences in myostatin protein distribution in the muscle fibers between the transgenic and wild-type mice. Main individual muscles increased by 76-152% in the transgenic mice over their wild-type littermate mice at 12 months of age. A large number of nuclei were localized in the central and basal lamina of the myofibers in the transgenic mice as the number of nuclei per fiber and 100um2 area was significantly higher in transgenic mice than wild-type mice. By systemic comparisons of global mRNA expression patterns between transgenic mice and wild-type littermates using microarray and qRT-PCR techniques, we have identified distinct gene expression patterns to support adult muscle build-up by myostatin propeptide, which are comprised of enhanced expressions of myogenic regulatory factors and extracelullar matrix components, and differentially down-regulated expressions of genes related to protein degradation and mitochondrial ATP synthesis. Conclusion: The results present a coordinated pattern of gene expressions for reduced energy utilization during muscle build-up in adult stage. Enhanced muscle buildup by myostatin propeptide is sustained by reduced ATP synthesis as a result of a decreased activity of protein degradation. Myostatin propeptide may have a therapeutic application to the treatment of clinical muscle wasting problems by depressing myostatin activity. http://www.biomedcentral.com/1471-2164/10/305 Baoping Zhao Eileena Li Robert Wall Jinzeng Yang BMC Genomics 2009, 10:305 2009-07-08T00:00:00Z doi:10.1186/1471-2164-10-305 BMC Genomics 1471-2164 10 305 2009-07-08T00:00:00Z PDF Background: ATP-dependent chromatin remodeling and the covalent modification of histones play central roles in determining chromatin structure and function. Although several specific interactions between these two activities have been elaborated, the global landscape remains to be elucidated. Results: In this paper, we have developed a computational method to generate the first genome-wide landscape of interactions between ATP-dependent chromatin remodeling and the covalent modification of histones in Saccharomyces cerevisiae. Our method succeeds in identifying known interactions and uncovers many previously unknown interactions between these two activities. Analysis of the genome-wide picture revealed that transcription-related modifications tend to interact with more chromatin remodelers. Our results also demonstrate that most chromatin remodeling-modification interactions act via interactions of remodelers with both histone-modifying enzymes and histone residues. We also found that the co-occurrence of both modification and remodeling has significantly different influences on multiple gene features (e.g. nucleosome occupancy) compared with the presence of either one. Conclusions: We gave the first genome-wide picture of ATP-dependent chromatin remodeling-histone modification interactions. We also revealed how these two activities work together to regulate chromatin structure and function. Our results suggest that distinct strategies for regulating chromatin activity are selectively employed by genes with different properties. http://www.biomedcentral.com/1471-2164/10/304 Zhiming Dai Xianhua Dai Qian Xiang Jihua Feng Jiang Wang Yangyang Deng Caisheng He BMC Genomics 2009, 10:304 2009-07-08T00:00:00Z doi:10.1186/1471-2164-10-304 BMC Genomics 1471-2164 10 304 2009-07-08T00:00:00Z PDF Background: BackgroundTranscriptionally quiescent spermatozoa have been established to be a repository of mRNA coding for several functionally essential cellular proteins. This entourage of mRNA is envisaged to be involved in post-fertilization and early embryogenesis. Minisatellites tagged with mRNA transcripts have been implicated with gene organization, regulation and function. However, the organization and expression of the minisatellite tagged transcript diversity, particularly in spermatozoa, remains unclear. Results: In the present study, we identified and characterized 12 mRNA transcripts from the spermatozoa of water buffalo Bubalus bubalis employing minisatellite associated sequence amplification (MASA) and a consensus sequence of 33.15 repeat loci. Of these 33.15 tagged transcripts, only one was found to be homologous to Bovine steroid 21-hydroxylase (P-450-c21) gene. Other ten transcripts showed significant similarity with various mRNAs or chromosomal contigs across the species. The remaining one construed to be novel since this was unreported in the database (NCBI GenBank). All these uncharacterized and known transcripts showed highest expression in testis and spermatozoa compared to that in somatic tissues and ovary. Of these 12 mRNA transcripts, 4 showed differential expression in the forebrain and hindbrain of buffalo. Moreover, genes corresponding to all the 33.15 tagged spermatozoal transcripts were found to be conserved across 13 other species analyzed. Conclusions: Our results show MASA as an important tool to capture mRNA transcript diversity tagged with minisatellites in the spermatozoa. Comprehensive characterization of these transcripts is envisaged to augment our understanding on the genes involved in testicular functions and sustenance of a viable paternal genome during pre- and post- fertilization events and early stages of development. Prospects of this approach in genome analysis in general and comparative genomics in particular are highlighted. http://www.biomedcentral.com/1471-2164/10/303 Jyoti Srivastava Sanjay Premi Sudhir Kumar Sher Ali BMC Genomics 2009, 10:303 2009-07-07T00:00:00Z doi:10.1186/1471-2164-10-303 BMC Genomics 1471-2164 10 303 2009-07-07T00:00:00Z PDF Background: The Gram-negative bacterium Photorhabdus asymbiotica (Pa) has been recovered from human infections in both North America and Australia. Recently, Pa has been shown to have a nematode vector that can also infect insects, like its sister species the insect pathogen P. luminescens (Pl). To understand the relationship between pathogenicity to insects and humans in Photorhabdus we have sequenced the complete genome of Pa strain ATCC43949 from North America. This strain (formerly referred to as Xenorhabdus luminescens strain 2) was isolated in 1977 from the blood of an 80 year old female patient with endocarditis, in Maryland, USA. Here we compare the complete genome of Pa ATCC43949 with that of the previously sequenced insect pathogen P. luminescens strain TT01 which was isolated from its entomopathogenic nematode vector collected from soil in Trinidad and Tobago. Results: We found that the human pathogen Pa had a smaller genome (5,064,808 bp) than that of the insect pathogen Pl (5,688,987 bp) but that each pathogen carries approximately one megabase of DNA that is unique to each strain. The reduced size of the Pa genome is associated with a smaller diversity in insecticidal genes such as those encoding the Toxin complexes (Tc's), Makes caterpillars floppy (Mcf) toxins and the Photorhabdus Virulence Cassettes (PVCs). The Pa genome, however, also shows the addition of a plasmid related to pMT1 from Yersinia pestis and several novel pathogenicity islands including a novel Type Three Secretion System (TTSS) encoding island. Together these data suggest that Pa may show virulence against man via the acquisition of the pMT1-like plasmid and specific effectors, such as SopB, that promote its persistence inside human macrophages. Interestingly the loss of insecticidal genes in Pa is not reflected by a loss of pathogenicity towards insects. Conclusions: Our results suggest that North American isolates of Pa have acquired virulence against man via the acquisition of a plasmid and specific virulence factors with similarity to those shown to play roles in pathogenicity against humans in other bacteria. http://www.biomedcentral.com/1471-2164/10/302 Paul Wilkinson Nicholas Waterfield Lisa Crossman Craig Corton Maria Sanchez-Contreras Isabella Vlisidou Andrew Barron Alexandra Bignell Louise Clark Jon Doggett Douglas Ormond Matthew Mayho Nathalie Bason Frances Smith Mark Simmonds Claire Arrowsmith Carol Churcher David Harris Nicholas Thompson Michael Quail Julian Parkhill Richard ffrench-Constant BMC Genomics 2009, 10:302 2009-07-07T00:00:00Z doi:10.1186/1471-2164-10-302 BMC Genomics 1471-2164 10 302 2009-07-07T00:00:00Z PDF Background: GLV-1h68 is an attenuated recombinant vaccinia virus (VACV) that selectively colonizes established human xenografts inducing their complete regression. Results: Here, we explored xenograft/VACV/host interactions in vivo adopting organism-specific expression arrays and tumor cell/VACV in vitro comparing VACV replication patterns. There were no clear-cut differences in vitro among responding and non-responding tumors, however, tumor rejection was associated in vivo with activation of interferon-stimulated genes (ISGs) and innate immune host's effector functions (IEFs) correlating with VACV colonization of the xenografts. These signatures precisely reproduce those observed in humans during immune-mediated tissue-specific destruction (TSD) that causes tumor or allograft rejection, autoimmunity or clearance of pathogens. We recently defined these common pathways in the "immunologic constant of rejection" hypothesis (ICR). Conclusions: This study provides the first prospective validation of a universal mechanism associated with TSD. Thus, xenograft infection by oncolytic VACV, beyond offering a promising therapy of established cancers, may represent a reliable pre-clinical model to test therapeutic strategies aimed at modulating the central pathways leading to TSD; this information may lead to the identification of principles that could refine the treatment of cancer and chronic infection by immune stimulation or autoimmunity and allograft rejection through immune tolerance. http://www.biomedcentral.com/1471-2164/10/301 Andrea Worschech Nanhai Chen Yong Yu Qian Zhang Zoltan Pos Stephanie Weibel Viktoria Raab Marianna Sabatino Alessandro Monaco Hui Liu Vladia Monsurro R Buller David Stroncek Ena Wang Aladar Szalay Francesco Marincola BMC Genomics 2009, 10:301 2009-07-07T00:00:00Z doi:10.1186/1471-2164-10-301 BMC Genomics 1471-2164 10 301 2009-07-07T00:00:00Z PDF Background: Male mosquitoes do not feed on blood and are not involved in delivery of pathogens to humans. Consequently, they are seldom the subjects of research, which results in a very poor understanding of their biology. To gain insights into male developmental processes we sought to identify genes transcribed exclusively in the reproductive tissues of male Anopheles gambiae pupae. Results: Using a cDNA subtraction strategy, five male-specifically or highly male-biased expressed genes were isolated, four of which remain unannotated in the An. gambiae genome. Spatial and temporal expression patterns suggest that each of these genes is involved in the mid-late stages of spermatogenesis. Their sequences are rapidly evolving; however, two genes possess clear homologs in a wide range of taxa and one of these probably acts in a sperm motility control mechanism conserved in many organisms, including humans. The other three genes have no match to sequences from non-mosquito taxa, thus can be regarded as orphans. RNA in situ hybridization demonstrated that one of the orphans is transcribed in spermatids, which suggests its involvement in sperm maturation. Two other orphans have unknown functions. Expression analysis of orthologs of all five genes indicated that male-biased transcription was not conserved in the majority of cases in Aedes and Culex. Conclusions: Discovery of testis-expressed orphan genes in mosquitoes opens new prospects for the development of innovative control methods. The orphan encoded proteins may represent unique targets of selective anti-mosquito sterilizing agents that will not affect non-target organisms. http://www.biomedcentral.com/1471-2164/10/300 Elzbieta Krzywinska Jaroslaw Krzywinski BMC Genomics 2009, 10:300 2009-07-06T00:00:00Z doi:10.1186/1471-2164-10-300 BMC Genomics 1471-2164 10 300 2009-07-06T00:00:00Z PDF Background: In-depth sequencing analysis has not been able to determine the overall complexity of transcriptional activity of a plant organ or tissue sample. In some cases, deep parallel sequencing of Expressed Sequence Tags (ESTs), although not yet optimized for the sequencing of cDNAs, has represented an efficient procedure for validating gene prediction and estimating overall gene coverage. This approach could be very valuable for complex plant genomes. In addition, little emphasis has been given to efforts aiming at an estimation of the overall transcriptional universe found in a multicellular organism at a specific developmental stage. Results: To explore, in depth, the transcriptional diversity in an ancient maize landrace, we developed a protocol to optimize the sequencing of cDNAs and performed 4 consecutive GS20-454 pyrosequencing runs of a cDNA library obtained from 2 week-old Palomero Toluqueno maize plants. The protocol reported here allowed obtaining over 90% of informative sequences. These GS20-454 runs generated over 1.5 Million reads, representing the largest amount of sequences reported from a single plant cDNA library. A collection of 367,391 quality-filtered reads (30.09 Mb) from a single run was sufficient to identify transcripts corresponding to 34% of public maize ESTs databases; total sequences generated after 4 filtered runs increased this coverage to 50%. Comparisons of all 1.5 Million reads to the Maize Assembled Genomic Islands (MAGIs) provided evidence for the transcriptional activity of 11% of MAGIs. We estimate that 5.67% (86,069 sequences) do not align with public ESTs or annotated genes, potentially representing new maize transcripts. Following the assembly of 74.4% of the reads in 65,493 contigs, real-time PCR of selected genes confirmed a predicted correlation between the abundance of GS20-454 sequences and corresponding levels of gene expression. Conclusions: A protocol was developed that significantly increases the number, length and quality of cDNA reads using massive 454 parallel sequencing. We show that recurrent 454 pyrosequencing of a single cDNA sample is necessary to attain a thorough representation of the transcriptional universe present in maize, that can also be used to estimate transcript abundance of specific genes. This data suggests that the molecular and functional diversity contained in the vast native landraces remains to be explored, and that large-scale transcriptional sequencing of a presumed ancestor of the modern maize varieties represents a valuable approach to characterize the functional diversity of maize for future agricultural and evolutionary studies. http://www.biomedcentral.com/1471-2164/10/299 Julio Vega-Arreguin Enrique Ibarra-Laclette Beatriz Jimenez-Moraila Octavio Martinez Jean Philippe Vielle-Calzada Luis Herrera-Estrella Alfredo Herrera-Estrella BMC Genomics 2009, 10:299 2009-07-06T00:00:00Z doi:10.1186/1471-2164-10-299 BMC Genomics 1471-2164 10 299 2009-07-06T00:00:00Z PDF Background: An animal model commonly used to investigate pathways and potential therapeutic interventions relevant to abdominal aortic aneurysm (AAA) involves subcutaneous infusion of angiotensin II within the apolipoprotein E deficient mouse. The aim of this study was to investigate genes differentially expressed in aneurysms forming within this mouse model in order to assess the relevance of this model to human AAA Results: Using microarrays we identified genes relevant to aneurysm formation within apolipoprotein E deficient mice. Firstly we investigated genes differentially expressed in the aneurysm prone segment of the suprarenal aorta in these mice. Secondly we investigated genes that were differentially expressed in the aortas of mice developing aneurysms relative to those that did not develop aneurysms in response to angiotensin II infusion. Our findings suggest that a host of inflammation and extracellular matrix remodelling pathways are upregulated within the aorta in mice developing aneurysms. Kyoto Encyclopedia of Genes and Genome categories enriched in the aortas of mice with aneurysms included cytokine-cytokine receptor interaction, leukocyte transendothelial migration, natural killer cell mediated cytotoxicity and hematopoietic cell lineage. Genes associated with extracellular matrix remodelling, such as a range of matrix metalloproteinases were also differentially expressed in relation to aneurysm formation. Conclusions: This study is the first report describing whole genome expression arrays in the apolipoprotein E deficient mice in relation to aneurysm formation. The findings suggest that the pathways believed to be critical in human AAA are also relevant to aneurysm formation in this mouse model. The findings therefore support the value of this model to investigate interventions and mechanisms of human AAA. http://www.biomedcentral.com/1471-2164/10/298 Catherine Rush Moses Nyara Joseph Moxon Alexandra Trollope Bradford Cullen Jonathan Golledge BMC Genomics 2009, 10:298 2009-07-06T00:00:00Z doi:10.1186/1471-2164-10-298 BMC Genomics 1471-2164 10 298 2009-07-06T00:00:00Z PDF