Sat, 26 Jul 2008 07:56:22 BST CiteULike: raiyar's library [213 articles] http://www.citeulike.org/user/raiyar CiteULike.org en-gb Copyright © 2004-2008 citeulike.org http://www.citeulike.org/user/raiyar/article/2825500 <i>Gene Therapy, Vol. aop, No. current.</i><br /><br />Defects of the mitochondrial genome cause a wide variety of clinical disorders. Except for rare cases where surgery or transplant is indicated, there is no effective treatment for patients. Genetic-based therapies are consequently being considered. On account of the difficulties associated with mitochondrial (mt) transfection, alternative approaches whereby mitochondrial genes can be engineered and introduced into the nucleus (allotopic expression) are being attempted with some success, at least in cultured cells. Defects in the activities of multi-subunit complexes of the oxidative phosphorylation apparatus have been circumvented by the targeted expression of simple single subunit enzymes from other species (xenotopic expression). Although far from the clinic, these approaches show promise. Similarly, nuclear transfection with genes encoding restriction endonucleases or sequence-specific zinc finger-binding proteins destined for mitochondria has also proved successful in targeting mtDNA-borne pathogenic mutations. This is particularly important, as mutated mtDNA is often found in cells that also contain normal copies of the genome, a situation termed heteroplasmy. Shifting the levels of heteroplasmy towards the normal mtDNA has become the goal of a variety of invasive and non-invasive methods, which are also highlighted in this review. Progress and prospects: gene therapy for mitochondrial DNA disease DS Kyriakouli P Boesch RW Taylor RN Lightowlers doi:10.1038/gt.2008.91 Gene Therapy, Vol. aop, No. current. 2008-05-23T14:15:42-00:00 Gene Therapy 0969-7128 aop current Nature Publishing Group allotopic disease mtdna review therapeutic http://www.citeulike.org/user/raiyar/article/1038480 <i>Cell Cycle, Vol. 5, No. 22. (November 2006), pp. 2613-2625.</i><br /><br />Recent completion of the initial phase of a haplotype map of human genome (www.hapmap.org) provides opportunity for integrative analysis on a genome-wide scale of microarray-based gene expression profiling and SNP variation patterns for discovery of cancer-causing genes and genetic markers of therapy outcome. Here we applied this approach for analysis of SNPs of cancer-associated genes, expression profiles of which predicts the likelihood of treatment failure and death after therapy in patients diagnosed with multiple types of cancer. Unexpectedly, this analysis reveals a common SNP pattern for a majority (60 of 74; 81%) of analyzed cancer treatment outcome predictor (CTOP) genes. Our analysis suggests that heritable germ-line genetic variations driven by geographically localized form of natural selection determining population differentiations may have a significant impact on cancer treatment outcome by influencing the individual's gene expression profile. We demonstrate a translational utility of this approach by building a highly informative CTOP algorithm combining prognostic power of multiple gene expression-based CTOP models derived from signatures of oncogenic pathways associated with activation of BMI1; Myc; Her2/neu; Ras; beta-catenin; Suz12; E2F; and CCND1 oncogenes. Application of a CTOP algorithm to large databases of early-stage breast and prostate tumors identifies cancer patients with 100% probability of a cure with existing cancer therapies as well as patients with nearly 100% likelihood of treatment failure, thus providing a clinically feasible framework essential for introduction of rational evidence-based individualized therapy selection and prescription protocols. Our analysis indicates that genetic determinants of human disease susceptibility and severity are encoded by population differentiation SNP variants. Evolution of these SNPs is driven by geographically-localized form of natural selection causing population differentiation. Recent analysis identifies a class of SNPs regulating gene expression in normal individuals and likely determining unique genome-wide expression profiles of each individual. We propose that critical disease-causing combinations of SNP variants arise from SNPs regulating mRNA levels and determining genome-wide haplotype patterns of individual's disease susceptibility. Integration of HapMap-based SNP pattern analysis and gene expression profiling reveals common SNP profiles for cancer therapy outcome predictor genes. GV Glinsky Cell Cycle, Vol. 5, No. 22. (November 2006), pp. 2613-2625. 2007-01-12T16:54:19-00:00 2006 Cell Cycle 1551-4005 5 22 2613 2625 cancer disease ellstalk expression integration snp variant http://www.citeulike.org/user/raiyar/article/2986165 <i>Nat Rev Drug Discov, Vol. 1, No. 1. (January 2002), pp. 37-44.</i> The genetic basis of variability in drug responses Dan Roden Alfred George doi:10.1038/nrd705 Nat Rev Drug Discov, Vol. 1, No. 1. (January 2002), pp. 37-44. 2008-07-10T22:32:51-00:00 2002 Nat Rev Drug Discov 1 1 37 44 compound ellstalk genetic pharmacogen review variant http://www.citeulike.org/user/raiyar/article/163580 <i>Science, Vol. 286, No. 5439. (15 October 1999), pp. 531-537.</i><br /><br />Although cancer classification has improved over the past 30 years, there has been no general approach for identifying new cancer classes (class discovery) or for assigning tumors to known classes (class prediction). Here, a generic approach to cancer classification based on gene expression monitoring by DNA microarrays is described and applied to human acute leukemias as a test case. A class discovery procedure automatically discovered the distinction between acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) without previous knowledge of these classes. An automatically derived class predictor was able to determine the class of new leukemia cases. The results demonstrate the feasibility of cancer classification based solely on gene expression monitoring and suggest a general strategy for discovering and predicting cancer classes for other types of cancer, independent of previous biological knowledge. Molecular Classification of Cancer: Class Discovery and Class Prediction by Gene Expression Monitoring TR Golub DK Slonim P Tamayo C Huard M Gaasenbeek JP Mesirov H Coller ML Loh JR Downing MA Caligiuri CD Bloomfield ES Lander doi:10.1126/science.286.5439.531 Science, Vol. 286, No. 5439. (15 October 1999), pp. 531-537. 2005-04-18T17:00:28-00:00 1999 Science 286 5439 531 537 analysis basis cancer disease ellstalk expression prediction http://www.citeulike.org/user/raiyar/article/2984367 <i>Nature biotechnology, Vol. 22, No. 10. (October 2004), pp. 1215-1217.</i> The impact of systems approaches on biological problems in drug discovery. L Hood RM Perlmutter doi:10.1038/nbt1004-1215 Nature biotechnology, Vol. 22, No. 10. (October 2004), pp. 1215-1217. 2008-07-10T09:04:50-00:00 2004 Nature biotechnology 1087-0156 22 10 1215 1217 compound disease ellstalk medicine pharmacogen review systems http://www.citeulike.org/user/raiyar/article/2981139 <i>Nature reviews. Genetics, Vol. 5, No. 9. (September 2004), pp. 669-676.</i><br /><br />Physicians have long been aware of the subtle differences in the responses of patients to medication. The recognition that a part of this variation is inherited, and therefore predictable, created the field of pharmacogenetics fifty years ago. Knowing the gene variants that cause differences among patients has the potential to allow 'personalized' drug therapy and to avoid therapeutic failure and serious side effects. Pharmacogenetics - five decades of therapeutic lessons from genetic diversity. UA Meyer doi:10.1038/nrg1428 Nature reviews. Genetics, Vol. 5, No. 9. (September 2004), pp. 669-676. 2008-07-09T17:51:31-00:00 2004 Nature reviews. Genetics 1471-0056 5 9 669 676 disease ellstalk genetic human pharmacogen variant http://www.citeulike.org/user/raiyar/article/2930557 <i>Genetics, Vol. 179, No. 2. (June 2008), pp. 727-735.</i> Mitochondria as chi. DC Wallace doi:10.1534/genetics.104.91769 Genetics, Vol. 179, No. 2. (June 2008), pp. 727-735. 2008-06-26T11:53:26-00:00 2008 Genetics 0016-6731 179 2 727 735 aging basis compound disease evolution interest medicine mitochondria mtdna population review http://www.citeulike.org/user/raiyar/article/2931034 <i>Science (New York, N.Y.), Vol. 308, No. 5730. (24 June 2005), pp. 1909-1911.</i><br /><br />To determine the role of reactive oxygen species in mammalian longevity, we generated transgenic mice that overexpress human catalase localized to the peroxisome, the nucleus, or mitochondria (MCAT). Median and maximum life spans were maximally increased (averages of 5 months and 5.5 months, respectively) in MCAT animals. Cardiac pathology and cataract development were delayed, oxidative damage was reduced, H2O2 production and H2O2-induced aconitase inactivation were attenuated, and the development of mitochondrial deletions was reduced. These results support the free radical theory of aging and reinforce the importance of mitochondria as a source of these radicals. Extension of murine life span by overexpression of catalase targeted to mitochondria. SE Schriner NJ Linford GM Martin P Treuting CE Ogburn M Emond PE Coskun W Ladiges N Wolf H Van Remmen DC Wallace PS Rabinovitch doi:10.1126/science.1106653 Science (New York, N.Y.), Vol. 308, No. 5730. (24 June 2005), pp. 1909-1911. 2008-06-26T12:33:53-00:00 2005 Science (New York, N.Y.) 1095-9203 308 5730 1909 1911 aging example localization mitochondria mitotarget projmt ros http://www.citeulike.org/user/raiyar/article/2931030 <i>Mitochondrion, Vol. 7, No. 1-2. (r 2007), pp. 45-52.</i><br /><br />Although mitochondrial disorders are increasingly being recognized, confirming a specific diagnosis remains a great challenge due to the genetic and clinical heterogeneity of the disease. The heteroplasmic nature of most pathogenic mitochondrial DNA mutations and the uncertainties of the clinical significance of novel mutations pose additional complications in making a diagnosis. Suspicion of mitochondrial disease among patients with multiple, seemingly unrelated neuromuscular and multi-system disorders should ideally be confirmed by the finding of deleterious mutations in genes involving mitochondrial biogenesis and functions. The genetics are complex, as the primary mutation can be either in the nuclear or the mitochondrial DNA (mtDNA). MtDNA mutations are often maternally inherited, but can also be sporadic or secondary to mutations in nuclear-encoded mitochondrial-targeted genes. Several well-defined clinical syndromes associated with specific mutations have been described, yet the genotype-phenotype correlation is often unclear and most patients do not fit within any defined syndrome and even within a family the expressivity of the disease can be extremely variable. This article describes examples representing diagnostic challenges of mitochondrial diseases that include the limitations of the mutation detection method, the occurrence of mitochondrial disease in families with another known neuromuscular disorder, atypical clinical presentation, the lack of correlation between the degree of mutant heteroplasmy and the severity of the disease, variable penetrance, and nuclear gene defects causing mtDNA depletion. Diagnostic challenges of mitochondrial DNA disorders. LJ Wong doi:10.1016/j.mito.2006.11.025 Mitochondrion, Vol. 7, No. 1-2. (r 2007), pp. 45-52. 2008-06-26T12:31:42-00:00 2007 Mitochondrion 1567-7249 7 1-2 45 52 diagnosis disease genetic mitochondria mtdna mutant review http://www.citeulike.org/user/raiyar/article/2930989 <i>Archives of ophthalmology, Vol. 111, No. 11. (November 1993), pp. 1525-1530.</i><br /><br />OBJECTIVE: Ophthalmologic and neurologic manifestations of the mitochondrial DNA mutation at position 8993 (MTATP*NARP8993) are reported and compared with previously published reports of patients with the 8993 mutation and other mitochondrial disorders. DESIGN: Pedigree analysis. SETTING: University referral center. PATIENTS: Eight subjects from two unrelated pedigrees that were positive for the mitochondrial DNA replacement mutation at nucleotide position 8993 were evaluated ophthalmologically and neurologically. RESULTS: Retinal abnormalities ranged from mild salt-and-pepper changes to severe retinitis pigmentosa-like changes with maculopathy. Neurologic manifestations were also highly variable and ranged from migraine headaches to severe dementia and Leigh's disease. CONCLUSIONS: The type and extent of retinal pigmentary changes and neurologic findings varied substantially, even among members of the same family. These changes, although not specific for the MTATP*NARP8993 mutation, are highly suggestive of mitochondrial disease. Variable retinal and neurologic manifestations in patients harboring the mitochondrial DNA 8993 mutation. RG Ortiz NJ Newman JM Shoffner AE Kaufman DA Koontz DC Wallace Archives of ophthalmology, Vol. 111, No. 11. (November 1993), pp. 1525-1530. 2008-06-26T12:03:21-00:00 1993 Archives of ophthalmology 0003-9950 111 11 1525 1530 basis disease mitochondria mtdna mutant narp http://www.citeulike.org/user/raiyar/article/2930556 <i>Annals of neurology, Vol. 63, No. 1. (January 2008), pp. 35-39.</i><br /><br />OBJECTIVE: Diverse and variable clinical features, a loose genotype-phenotype relationship, and presentation to different medical specialties have all hindered attempts to gauge the epidemiological impact of mitochondrial DNA (mtDNA) disease. Nevertheless, a clear understanding of its prevalence remains an important goal, particularly about planning appropriate clinical services. Consequently, the aim of this study was to accurately define the prevalence of mtDNA disease (primary mutation occurs in mtDNA) in the working-age population of the North East of England. METHODS: Adults with suspected mitochondrial disease in the North East of England were referred to a single neurology center for investigation from 1990 to 2004. Those with pathogenic mtDNA mutations were identified and pedigree analysis performed. For the midyear period of 2001, we calculated the minimum point prevalence of mtDNA disease for adults of working age (>16 and <60/65 years for female/male patients, respectively). RESULTS: In this population, we found that 9.2 in 100,000 people have clinically manifest mtDNA disease, making this one of the commonest inherited neuromuscular disorders. In addition, a further 16.5 in 100,000 children and adults younger than retirement age are at risk for development of mtDNA disease. INTERPRETATION: Through detailed pedigree analysis and active family tracing, we have been able to provide revised minimum prevalence figures for mtDNA disease. These estimates confirm that mtDNA disease is a common cause of chronic morbidity and is more prevalent than has been previously appreciated. Prevalence of mitochondrial DNA disease in adults. AM Schaefer R McFarland EL Blakely L He RG Whittaker RW Taylor PF Chinnery DM Turnbull doi:10.1002/ana.21217 Annals of neurology, Vol. 63, No. 1. (January 2008), pp. 35-39. 2008-06-26T11:52:13-00:00 2008 Annals of neurology 1531-8249 63 1 35 39 basis disease human mitochondria mtdna population statistics http://www.citeulike.org/user/raiyar/article/1509893 <i>Mamm Genome (26 July 2007)</i><br /><br />Testing hundreds of thousands of DNA markers in human, mouse, and other species for association to complex traits like disease is now a reality. However, information on how variations in DNA impact complex physiologic processes flows through transcriptional and other molecular networks. In other words, DNA variations impact complex diseases through the perturbations they cause to transcriptional and other biological networks, and these molecular phenotypes are intermediate to clinically defined disease. Because it is also now possible to monitor transcript levels in a comprehensive fashion, integrating DNA variation, transcription, and phenotypic data has the potential to enhance identification of the associations between DNA variation and diseases like obesity and diabetes, as well as characterize those parts of the molecular networks that drive these diseases. Toward that end, we review methods for integrating expression quantitative trait loci (eQTLs), gene expression, and clinical data to infer causal relationships among gene expression traits and between expression and clinical traits. We further describe methods to integrate these data in a more comprehensive manner by constructing coexpression gene networks that leverage pairwise gene interaction data to represent more general relationships. To infer gene networks that capture causal information, we describe a Bayesian algorithm that further integrates eQTLs, expression, and clinical phenotype data to reconstruct whole-gene networks capable of representing causal relationships among genes and traits in the network. These emerging network approaches, aimed at processing high-dimensional biological data by integrating data from multiple sources, represent some of the first steps in statistical genetics to identify multiple genetic perturbations that alter the states of molecular networks and that in turn push systems into disease states. Evolving statistical procedures that operate on networks will be critical to extracting information related to complex phenotypes like disease, as research goes beyond a single-gene focus. The early successes achieved with the methods described herein suggest that these more integrative genomics approaches to dissecting disease traits will significantly enhance the identification of key drivers of disease beyond what could be achieved by genetic association studies alone. Moving toward a system genetics view of disease. Solveig Sieberts Eric Schadt doi:10.1007/s00335-007-9040-6 Mamm Genome (26 July 2007) 2007-07-28T10:02:22-00:00 2007 Mamm Genome 0938-8990 expression genetic network qtl review statistics systems http://www.citeulike.org/user/raiyar/article/2610495 <i>The American Journal of Human Genetics, Vol. In Press, Corrected Proof</i><br /><br />The identification of genes associated with hereditary disorders has contributed to improving medical care and to a better understanding of gene functions, interactions, and pathways. However, there are well over 1500 Mendelian disorders whose molecular basis remains unknown. At present, methods such as linkage analysis can identify the chromosomal region in which unknown disease genes are located, but the regions could contain up to hundreds of candidate genes. In this work, we present a method for prioritization of candidate genes by use of a global network distance measure, random walk analysis, for definition of similarities in protein-protein interaction networks. We tested our method on 110 disease-gene families with a total of 783 genes and achieved an area under the ROC curve of up to 98% on simulated linkage intervals of 100 genes surrounding the disease gene, significantly outperforming previous methods based on local distance measures. Our results not only provide an improved tool for positional-cloning projects but also add weight to the assumption that phenotypically similar diseases are associated with disturbances of subnetworks within the larger protein interactome that extend beyond the disease proteins themselves. Walking the Interactome for Prioritization of Candidate Disease Genes Sebastian Kohler Sebastian Bauer Denise Horn Peter Robinson doi:10.1016/j.ajhg.2008.02.013 The American Journal of Human Genetics, Vol. In Press, Corrected Proof 2008-03-29T10:25:03-00:00 The American Journal of Human Genetics In Press, Corrected Proof disease genetic interaction methodspaper network prediction http://www.citeulike.org/user/raiyar/article/2620752 <i>Genome Res., Vol. 18, No. 4. (1 April 2008), pp. 644-652.</i><br /><br />During a decade of proof-of-principle analysis in model organisms, protein networks have been used to further the study of molecular evolution, to gain insight into the robustness of cells to perturbation, and for assignment of new protein functions. Following these analyses, and with the recent rise of protein interaction measurements in mammals, protein networks are increasingly serving as tools to unravel the molecular basis of disease. We review promising applications of protein networks to disease in four major areas: identifying new disease genes; the study of their network properties; identifying disease-related subnetworks; and network-based disease classification. Applications in infectious disease, personalized medicine, and pharmacology are also forthcoming as the available protein network information improves in quality and coverage. 10.1101/gr.071852.107 Protein networks in disease Trey Ideker Roded Sharan doi:10.1101/gr.071852.107 Genome Res., Vol. 18, No. 4. (1 April 2008), pp. 644-652. 2008-04-01T18:31:26-00:00 2008 Genome Res. 18 4 644 652 disease ellstalk methodspaper network prediction proteomics http://www.citeulike.org/user/raiyar/article/2907736 <i>The Journal of clinical endocrinology and metabolism, Vol. 93, No. 4. (April 2008), pp. 1097-1104.</i><br /><br />Genetic advances in endocrine neoplasia provided the paradigm for the practice of clinical cancer genetics: germline RET mutations in multiple endocrine neoplasia type 2. In the last 14 yr, both genetics and -omics advances have occurred, almost exponentially in the last 5 yr. The time has come to reevaluate recent advances in genomic medicine's promise to revolutionize personalized healthcare in the context of endocrine neoplasias. This update focuses on two examples of endocrine neoplasias, those of the thyroid and of the adrenal, and discusses recent advances in germline and somatic genetics and genomics, as they relate to clinical application. Update on the molecular diagnosis of endocrine tumors: toward -omics-based personalized healthcare? F Weber C Eng doi:10.1210/jc.2008-0212 The Journal of clinical endocrinology and metabolism, Vol. 93, No. 4. (April 2008), pp. 1097-1104. 2008-06-19T14:38:43-00:00 2008 The Journal of clinical endocrinology and metabolism 0021-972X 93 4 1097 1104 disease ellstalk human review http://www.citeulike.org/user/raiyar/article/2626768 <i>Nature, Vol. 452, No. 7187. (02 April 2008), pp. 564-570.</i><br /><br />Therapies for patients with cancer have changed gradually over the past decade, moving away from the administration of broadly acting cytotoxic drugs towards the use of more-specific therapies that are targeted to each tumour. To facilitate this shift, tests need to be developed to identify those individuals who require therapy and those who are most likely to benefit from certain therapies. In particular, tests that predict the clinical outcome for patients on the basis of the genes expressed by their tumours are likely to increasingly affect patient management, heralding a new era of personalized medicine. Enabling personalized cancer medicine through analysis of gene-expression patterns Laura René Bernards doi:10.1038/nature06915 Nature, Vol. 452, No. 7187. (02 April 2008), pp. 564-570. 2008-04-03T16:42:35-00:00 2008 Nature 0028-0836 452 7187 564 570 Nature Publishing Group cancer disease ellstalk expression human review http://www.citeulike.org/user/raiyar/article/1369386 <i>Nature, Vol. 447, No. 7145. (7 June 2007), pp. 661-678.</i> Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls The Wellcome Trust Case Control Consortium doi:10.1038/nature05911 Nature, Vol. 447, No. 7145. (7 June 2007), pp. 661-678. 2007-06-07T05:46:18-00:00 2007 Nature 447 7145 661 678 analysis complex_trait disease genetic human methodspaper qtl snp variant http://www.citeulike.org/user/raiyar/article/119335 <i>Nucleic Acids Res, Vol. 33 Database Issue (1 January 2005)</i><br /><br />Online Mendelian Inheritance in Man (OMIM) is a comprehensive, authoritative and timely knowledgebase of human genes and genetic disorders compiled to support human genetics research and education and the practice of clinical genetics. Started by Dr Victor A. McKusick as the definitive reference Mendelian Inheritance in Man, OMIM (http://www.ncbi.nlm.nih.gov/omim/) is now distributed electronically by the National Center for Biotechnology Information, where it is integrated with the Entrez suite of databases. Derived from the biomedical literature, OMIM is written and edited at Johns Hopkins University with input from scientists and physicians around the world. Each OMIM entry has a full-text summary of a genetically determined phenotype and/or gene and has numerous links to other genetic databases such as DNA and protein sequence, PubMed references, general and locus-specific mutation databases, HUGO nomenclature, MapViewer, GeneTests, patient support groups and many others. OMIM is an easy and straightforward portal to the burgeoning information in human genetics. Online Mendelian Inheritance in Man (OMIM), a knowledgebase of human genes and genetic disorders. A Hamosh AF Scott JS Amberger CA Bocchini VA McKusick Nucleic Acids Res, Vol. 33 Database Issue (1 January 2005) 2005-03-10T07:30:04-00:00 2005 Nucleic Acids Res 1362-4962 33 Database Issue db disease methodspaper http://www.citeulike.org/user/raiyar/article/2096382 <i>Nature, Vol. 414, No. 6862. (22 November 2001), pp. 450-453.</i><br /><br />Microsporidia are obligate intracellular parasites infesting many animal groups. Lacking mitochondria and peroxysomes, these unicellular eukaryotes were first considered a deeply branching protist lineage that diverged before the endosymbiotic event that led to mitochondria. The discovery of a gene for a mitochondrial-type chaperone combined with molecular phylogenetic data later implied that microsporidia are atypical fungi that lost mitochondria during evolution. Here we report the DNA sequences of the 11 chromosomes of the approximately 2.9-megabase (Mb) genome of Encephalitozoon cuniculi (1,997 potential protein-coding genes). Genome compaction is reflected by reduced intergenic spacers and by the shortness of most putative proteins relative to their eukaryote orthologues. The strong host dependence is illustrated by the lack of genes for some biosynthetic pathways and for the tricarboxylic acid cycle. Phylogenetic analysis lends substantial credit to the fungal affiliation of microsporidia. Because the E. cuniculi genome contains genes related to some mitochondrial functions (for example, Fe-S cluster assembly), we hypothesize that microsporidia have retained a mitochondrion-derived organelle. Genome sequence and gene compaction of the eukaryote parasite Encephalitozoon cuniculi. MD Katinka S Duprat E Cornillot G Méténier F Thomarat G Prensier V Barbe E Peyretaillade P Brottier P Wincker F Delbac H El Alaoui P Peyret W Saurin M Gouy J Weissenbach CP Vivarès doi:10.1038/35106579 Nature, Vol. 414, No. 6862. (22 November 2001), pp. 450-453. 2007-12-12T01:39:56-00:00 2001 Nature 0028-0836 414 6862 450 453 evolution genomics methodspaper mitochondria parts-list prediction http://www.citeulike.org/user/raiyar/article/2707822 <i>Médecine sciences : M/S, Vol. 23, No. 5. (May 2007), pp. 519-525.</i><br /><br />Mitochondrial disorders can not be ignored anymore in most medical areas. They include specific and widespread organ involvement, with tissue degeneration or tumor formation, being the target of numerous viruses, e.g. the HIV. Primary or secondary actors, mitochondrial dysfunctions are also supposedly playing a role in the ageing process. Despite the progresses made in the identification of their molecular bases, nearly all remains to be done as regards therapy. Research dealing with mitochondrial physiology and pathology has a long history in France and is thus not a surprise if four French teams, coming from these fundamental domains, are involved in the challenge to find ways to fight these diseases. The directions described are working tracks which promise to be long and full of pitfalls. Being original, they share a part of risk and uncertainty, but they are also with great potential with high stakes if considering the impact of these diseases. [Targeting allotopic material to the mitochondrial compartment: new tools for better understanding mitochondrial physiology and prospect for therapy] P Rustin H T Jacobs A Dietrich R N Lightowlers I Tarassov M Corral-Debrinski Médecine sciences : M/S, Vol. 23, No. 5. (May 2007), pp. 519-525. 2008-04-23T14:37:39-00:00 2007 Médecine sciences : M/S 0767-0974 23 5 519 525 allotopic mitochondria mitotarget projmt review http://www.citeulike.org/user/raiyar/article/2707759 <i>Rejuvenation research, Vol. 10, No. 2. (June 2007), pp. 127-144.</i><br /><br />The possibility of synthesizing mitochondrial DNA (mtDNA)-coded proteins in the cytosolic compartment, called allotopic expression, provides an attractive option for genetic treatment of human diseases caused by mutations of the corresponding genes. However, it is now appreciated that the high hydrophobicity of proteins encoded by the mitochondrial genome represents a strong limitation on their mitochondrial import when translated in the cytosol. Recently, we optimized the allotopic expression of a recoded ATP6 gene in human cells, by forcing its mRNA to localize to the mitochondrial surface. In this study, we show that this approach leads to a long-lasting and complete rescue of mitochondrial dysfunction of fibroblasts harboring the neurogenic muscle weakness, ataxia and retinitis Pigmentosa T8993G ATP6 mutation or the Leber hereditary optic neuropathy G11778A ND4 mutation. The recoded ATP6 gene was associated with the cis-acting elements of SOD2, while the ND4 gene was associated with the cis-acting elements of COX10. Both ATP6 and ND4 gene products were efficiently translocated into the mitochondria and functional within their respective respiratory chain complexes. Indeed, the abilities to grow in galactose and to produce adenosine triphosphate (ATP) in vitro were both completely restored in fibroblasts allotopically expressing either ATP6 or ND4. Notably, in fibroblasts harboring the ATP6 mutation, allotopic expression of ATP6 led to the recovery of complex V enzymatic activity. Therefore, mRNA sorting to the mitochondrial surface represents a powerful strategy that could ultimately be applied in human therapy and become available for an array of devastating disorders caused by mtDNA mutations. Allotopic mRNA localization to the mitochondrial surface rescues respiratory chain defects in fibroblasts harboring mitochondrial DNA mutations affecting complex I or v subunits. C Bonnet V Kaltimbacher S Ellouze S Augustin P Bénit V Forster P Rustin JA Sahel M Corral-Debrinski doi:10.1089/rej.2006.0526 Rejuvenation research, Vol. 10, No. 2. (June 2007), pp. 127-144. 2008-04-23T14:14:54-00:00 2007 Rejuvenation research 1549-1684 10 2 127 144 allotopic atp6 human mitochondria mitotarget mtdna projmt http://www.citeulike.org/user/raiyar/article/2707557 <i>The Journal of biological chemistry, Vol. 278, No. 46. (14 November 2003), pp. 45109-45116.</i><br /><br />We have previously proposed that a single translation product of the FUM1 gene encoding fumarase is distributed between the cytosol and mitochondria of Saccharomyces cerevisiae and that all fumarase translation products are targeted and processed in mitochondria before distribution. Thus, fumarase processed in mitochondria returns to the cytosol. In the current work, we (i) generated mutations throughout the coding sequence which resulted in fumarases with altered conformations that are targeted to mitochondria but have lost their ability to be distributed; (ii) showed by mass spectrometry that mature cytosolic and mitochondrial fumarase isoenzymes are identical; and (iii) showed that hsp70 chaperones in the cytosol (Ssa) and mitochondria (Ssc1) can affect fumarase distribution. The results are discussed in light of our model of targeting and distribution, which suggests that rapid folding of fumarase into an import-incompetent state provides the driving force for retrograde movement of the processed protein back to the cytosol through the translocation pore. Folding of fumarase during mitochondrial import determines its dual targeting in yeast. E Sass S Karniely O Pines doi:10.1074/jbc.M302344200 The Journal of biological chemistry, Vol. 278, No. 46. (14 November 2003), pp. 45109-45116. 2008-04-23T13:00:36-00:00 2003 The Journal of biological chemistry 0021-9258 278 46 45109 45116 localization mitochondria mitotarget yeast http://www.citeulike.org/user/raiyar/article/596796 <i>Proc Natl Acad Sci U S A, Vol. 97, No. 22. (24 October 2000), pp. 12115-12120.</i><br /><br />We introduce a computational method for identifying subcellular locations of proteins from the phylogenetic distribution of the homologs of organellar proteins. This method is based on the observation that proteins localized to a given organelle by experiments tend to share a characteristic phylogenetic distribution of their homologs-a phylogenetic profile. Therefore any other protein can be localized by its phylogenetic profile. Application of this method to mitochondrial proteins reveals that nucleus-encoded proteins previously known to be destined for mitochondria fall into three groups: prokaryote-derived, eukaryote-derived, and organism-specific (i.e., found only in the organism under study). Prokaryote-derived mitochondrial proteins can be identified effectively by their phylogenetic profiles. In the yeast Saccharomyces cerevisiae, 361 nucleus-encoded mitochondrial proteins can be identified at 50% accuracy with 58% coverage. From these values and the proportion of conserved mitochondrial genes, it can be inferred that approximately 630 genes, or 10% of the nuclear genome, is devoted to mitochondrial function. In the worm Caenorhabditis elegans, we estimate that there are approximately 660 nucleus-encoded mitochondrial genes, or 4% of its genome, with approximately 400 of these genes contributed from the prokaryotic mitochondrial ancestor. The large fraction of organism-specific and eukaryote-derived genes suggests that mitochondria perform specialized roles absent from prokaryotic mitochondrial ancestors. We observe measurably distinct phylogenetic profiles among proteins from different subcellular compartments, allowing the general use of prokaryotic genomes in learning features of eukaryotic proteins. Localizing proteins in the cell from their phylogenetic profiles. EM Marcotte I Xenarios AM van Der Bliek D Eisenberg doi:10.1073/pnas.220399497 Proc Natl Acad Sci U S A, Vol. 97, No. 22. (24 October 2000), pp. 12115-12120. 2006-04-24T09:27:50-00:00 2000 Proc Natl Acad Sci U S A 0027-8424 97 22 12115 12120 evolution localization mitochondria parts-list http://www.citeulike.org/user/raiyar/article/2528053 <i>Nature, Vol. 452, No. 7184., pp. 230-233.</i> The M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumour growth Heather Christofk Matthew Marian Harris Arvind Ramanathan Robert Gerszten Ru Wei Mark Fleming Stuart Schreiber Lewis Cantley doi:10.1038/nature06734 Nature, Vol. 452, No. 7184., pp. 230-233. 2008-03-13T16:21:14-00:00 Nature 0028-0836 452 7184 230 233 Nature Publishing Group cancer interest mitochondria respiration http://www.citeulike.org/user/raiyar/article/2698470 <i>Mitochondrion, Vol. 6, No. 5. (October 2006), pp. 252-257.</i><br /><br />The oxidative phosphorylation (OXPHOS) is the primary energy-producing process of all aerobic organisms and the only cellular function under the dual control of both the mitochondrial and the nuclear genomes. Functional characterization and evolutionary study of the OXPHOS system is of great importance for the understanding of many as yet unclear aspects of nucleus-mitochondrion genomic co-evolution and co-regulation gene networks. The MitoDrome database is a web-based database which provides genomic annotations about nuclear genes of Drosophila melanogaster encoding for mitochondrial proteins. Recently, MitoDrome has included a new section annotating genomic information about OXPHOS genes in Drosophila pseudoobscura and Anopheles gambiae and their comparative analysis with their Drosophila melanogaster and human counterparts. The introduction of this new comparative annotation section into MitoDrome is expected to be a useful resource for both functional and structural genomics related to the OXPHOS system. The MitoDrome database annotates and compares the OXPHOS nuclear genes of Drosophila melanogaster, Drosophila pseudoobscura and Anopheles gambiae. D D'Elia D Catalano F Licciulli A Turi G Tripoli D Porcelli C Saccone C Caggese doi:10.1016/j.mito.2006.07.001 Mitochondrion, Vol. 6, No. 5. (October 2006), pp. 252-257. 2008-04-21T23:22:44-00:00 2006 Mitochondrion 1567-7249 6 5 252 257 db drosophila methodspaper mitochondria parts-list http://www.citeulike.org/user/raiyar/article/2698415 <i>Nucleic acids research, Vol. 32, No. Database issue. (1 January 2004)</i><br /><br />MitoProteome is an object-relational mitochondrial protein sequence database and annotation system. The initial release contains 847 human mitochondrial protein sequences, derived from public sequence databases and mass spectrometric analysis of highly purified human heart mitochondria. Each sequence is manually annotated with primary function, subfunction and subcellular location, and extensively annotated in an automated process with data extracted from external databases, including gene information from LocusLink and Ensembl; disease information from OMIM; protein-protein interaction data from MINT and DIP; functional domain information from Pfam; protein fingerprints from PRINTS; protein family and family-specific signatures from InterPro; structure data from PDB; mutation data from PMD; BLAST homology data from NCBI NR; and proteins found to be related based on LocusLink and SWISS-PROT references and sequence and taxonomy data. By highly automating the processes of maintaining the MitoProteome Protein List and extracting relevant data from external databases, we are able to present a dynamic database, updated frequently to reflect changes in public resources. The MitoProteome database is publicly available at http://www. mitoproteome.org/. Users may browse and search MitoProteome, and access a complete compilation of data relevant to each protein of interest, cross-linked to external databases. MitoProteome: mitochondrial protein sequence database and annotation system. D Cotter P Guda E Fahy S Subramaniam Nucleic acids research, Vol. 32, No. Database issue. (1 January 2004) 2008-04-21T23:01:51-00:00 2004 Nucleic acids research 1362-4962 32 Database issue db methodspaper mitochondria parts-list proteomics http://www.citeulike.org/user/raiyar/article/100186 <i>Science, Vol. 303, No. 5659. (06 February 2004), pp. 808-813.</i><br /><br />A genetic interaction network containing [~]1000 genes and [~]4000 interactions was mapped by crossing mutations in 132 different query genes into a set of [~]4700 viable gene yeast deletion mutants and scoring the double mutant progeny for fitness defects. Network connectivity was predictive of function because interactions often occurred among functionally related genes, and similar patterns of interactions tended to identify components of the same pathway. The genetic network exhibited dense local neighborhoods; therefore, the position of a gene on a partially mapped network is predictive of other genetic interactions. Because digenic interactions are common in yeast, similar networks may underlie the complex genetics associated with inherited phenotypes in other organisms. Global Mapping of the Yeast Genetic Interaction Network Amy Tong Guillaume Lesage Gary Bader Huiming Ding Hong Xu Xiaofeng Xin James Young Gabriel Berriz Renee Brost Michael Chang Yiqun Chen Xin Cheng Gordon Chua Helena Friesen Debra Goldberg Jennifer Haynes Christine Humphries Grace He Shamiza Hussein Lizhu Ke Nevan Krogan Zhijian Li Joshua Levinson Hong Lu Patrice Menard Christella Munyana Ainslie Parsons Owen Ryan Raffi Tonikian Tania Roberts Anne-Marie Sdicu Jesse Shapiro Bilal Sheikh Bernhard Suter Sharyl Wong Lan Zhang Hongwei Zhu Christopher Burd Sean Munro Chris Sander Jasper Rine Jack Greenblatt Matthias Peter Anthony Bretscher Graham Bell Frederick Roth Grant Brown Brenda Andrews Howard Bussey Charles Boone doi:10.1126/science.1091317 Science, Vol. 303, No. 5659. (06 February 2004), pp. 808-813. 2005-02-21T20:30:21-00:00 2004 Science 303 5659 808 813 basis deletion genetic genomics interaction methodspaper network yeast http://www.citeulike.org/user/raiyar/article/168396 <i>Genome Res, Vol. 10, No. 8. (August 2000), pp. 1074-1077.</i> Guilt by association: contextual information in genome analysis. L Aravind doi:10.1101/gr.10.8.1074 Genome Res, Vol. 10, No. 8. (August 2000), pp. 1074-1077. 2005-04-23T08:32:31-00:00 2000 Genome Res 1088-9051 10 8 1074 1077 genomics interaction methodspaper network http://www.citeulike.org/user/raiyar/article/2079062 <i>(15 December 2001)</i><br /><br />In the 1990s, a new type of learning algorithm was developed, based on results from statistical learning theory: the Support Vector Machine (SVM). This gave rise to a new class of theoretically elegant learning machines that use a central concept of SVMs—-kernels--for a number of learning tasks. Kernel machines provide a modular framework that can be adapted to different tasks and domains by the choice of the kernel function and the base algorithm. They are replacing neural networks in a variety of fields, including engineering, information retrieval, and bioinformatics.<br /> <br /> <i>Learning with Kernels</i> provides an introduction to SVMs and related kernel methods. Although the book begins with the basics, it also includes the latest research. It provides all of the concepts necessary to enable a reader equipped with some basic mathematical knowledge to enter the world of machine learning using theoretically well-founded yet easy-to-use kernel algorithms and to understand and apply the powerful algorithms that have been developed over the last few years. Learning with Kernels: Support Vector Machines, Regularization, Optimization, and Beyond (Adaptive Computation and Machine Learning) Bernhard Schölkopf Alexander Smola (15 December 2001) 2007-12-08T16:45:46-00:00 2001 The MIT Press analysis basis methodspaper statistics technique http://www.citeulike.org/user/raiyar/article/493946 <i>Nature, Vol. 425, No. 6959. (16 October 2003), pp. 737-741.</i><br /><br />The availability of complete genomic sequences and technologies that allow comprehensive analysis of global expression profiles of messenger RNA have greatly expanded our ability to monitor the internal state of a cell. Yet biological systems ultimately need to be explained in terms of the activity, regulation and modification of proteins--and the ubiquitous occurrence of post-transcriptional regulation makes mRNA an imperfect proxy for such information. To facilitate global protein analyses, we have created a Saccharomyces cerevisiae fusion library where each open reading frame is tagged with a high-affinity epitope and expressed from its natural chromosomal location. Through immunodetection of the common tag, we obtain a census of proteins expressed during log-phase growth and measurements of their absolute levels. We find that about 80% of the proteome is expressed during normal growth conditions, and, using additional sequence information, we systematically identify misannotated genes. The abundance of proteins ranges from fewer than 50 to more than 10(6) molecules per cell. Many of these molecules, including essential proteins and most transcription factors, are present at levels that are not readily detectable by other proteomic techniques nor predictable by mRNA levels or codon bias measurements. Global analysis of protein expression in yeast. S Ghaemmaghami WK Huh K Bower RW Howson A Belle N Dephoure EK O'Shea JS Weissman doi:10.1038/nature02046 Nature, Vol. 425, No. 6959. (16 October 2003), pp. 737-741. 2006-02-05T10:34:50-00:00 2003 Nature 1476-4687 425 6959 737 741 ht methodspaper proteomics yeast http://www.citeulike.org/user/raiyar/article/2451391 <i>Genome Biology, Vol. 9 (29 February 2008), 209.</i> Proteomic view of mitochondrial function Kai Dimmer Doron Rapaport doi:10.1186/gb-2008-9-2-209 Genome Biology, Vol. 9 (29 February 2008), 209. 2008-03-01T14:07:15-00:00 2008 Genome Biology 1465-6906 9 209 methodspaper mitochondria proteomics review http://www.citeulike.org/user/raiyar/article/2696771 <i>Genome research, Vol. 18, No. 1. (January 2008), pp. 123-136.</i><br /><br />Mitochondrial dysfunction is associated with many human diseases. There has not been a systematic genetic approach for identifying regulators of basal mitochondrial biogenesis and function in higher eukaryotes. We performed a genome-wide RNA interference (RNAi) screen in Drosophila cells using mitochondrial Citrate synthase (CS) activity as the primary readout. We screened 13,071 dsRNAs and identified 152 genes that modulate CS activity. These modulators are involved in a wide range of biological processes and pathways including mitochondrial-related functions, transcriptional and translational regulation, and signaling pathways. Selected hits among the 152 genes were further analyzed for their effect on mitochondrial CS activity in transgenic flies or fly mutants. We confirmed a number of gene hits including HDAC6, Rpd3(HDAC1), CG3249, vimar, Src42A, klumpfuss, barren, and smt3 which exert effects on mitochondrial CS activities in vivo, demonstrating the value of Drosophila genome-wide RNAi screens for identifying genes and pathways that modulate mitochondrial function. Identification of novel modulators of mitochondrial function by a genome-wide RNAi screen in Drosophila melanogaster. J Chen X Shi R Padmanabhan Q Wang Z Wu SC Stevenson M Hild D Garza H Li doi:10.1101/gr.6940108 Genome research, Vol. 18, No. 1. (January 2008), pp. 123-136. 2008-04-21T14:34:13-00:00 2008 Genome research 1088-9051 18 1 123 136 drosophila methodspaper mitochondria parts-list rnai http://www.citeulike.org/user/raiyar/article/161814 <i>(09 August 2001)</i><br /><br />During the past decade there has been an explosion in computation and information technology. With it has come vast amounts of data in a variety of fields such as medicine, biology, finance, and marketing. The challenge of understanding these data has led to the development of new tools in the field of statistics, and spawned new areas such as data mining, machine learning, and bioinformatics. Many of these tools have common underpinnings but are often expressed with different terminology. This book descibes theimprtant ideas in these areas ina common conceptual framework. While the approach is statistical, the emphasis is on concepts rather than mathematics. Many examples are given, with a liberal use of color graphics. It should be a vluable resource for statisticians and anyone interested in data mining in science or industry. The book's coverage is broad, from supervised learing (prediction) to unsupervised learning. The many topics include neural networks, support vector machines, classification trees and boosting--the first comprehensive treatment of this topic in any book. Trevor Hastie, Robert Tibshirani, and Jerome Friedman are professors of statistics at Stanford University. They are prominent researchers in this area: Hastie and Tibshirani developed generalized additive models and wrote a popular book of that title. Hastie wrote much of the statistical modeling software in S-PLUS and invented principal curves and surfaces. Tibshirani proposed the Lasso and is co-author of the very successful An Introduction to the Bootstrap. Friedman is the co-inventor of many data-mining tools including CART, MARS, and projection pursuit. The Elements of Statistical Learning T Hastie R Tibshirani JH Friedman (09 August 2001) 2005-04-15T14:57:05-00:00 2001 Springer analysis basis integration methodspaper statistics technique http://www.citeulike.org/user/raiyar/article/2695807 <i>Science, Vol. 283, No. 5407. (5 March 1999), pp. 1482-1488.</i><br /><br />10.1126/science.283.5407.1482 Mitochondrial Diseases in Man and Mouse Douglas Wallace doi:10.1126/science.283.5407.1482 Science, Vol. 283, No. 5407. (5 March 1999), pp. 1482-1488. 2008-04-21T12:12:08-00:00 1999 Science 283 5407 1482 1488 basis disease human methodspaper mitochondria review http://www.citeulike.org/user/raiyar/article/2695783 <i>Biochimica et biophysica acta, Vol. 1659, No. 2-3. (6 December 2004), pp. 115-120.</i><br /><br />A number of epidemiological studies of mitochondrial disease have been carried out over the last decade, clearly demonstrating that mitochondrial disorders are far more common than was previously accepted. This review summarizes current knowledge of the prevalence of human mitochondrial disorders--data that has important implications for the provision of health care and adequate resources for research into the pathogenesis and treatment of these disorders. The epidemiology of mitochondrial disorders--past, present and future. AM Schaefer RW Taylor DM Turnbull PF Chinnery doi:10.1016/j.bbabio.2004.09.005 Biochimica et biophysica acta, Vol. 1659, No. 2-3. (6 December 2004), pp. 115-120. 2008-04-21T12:00:45-00:00 2004 Biochimica et biophysica acta 0006-3002 1659 2-3 115 120 disease methodspaper mitochondria parts-list review http://www.citeulike.org/user/raiyar/article/2682140 <i>Pediatrics, Vol. 120, No. 6. (December 2007), pp. 1326-1333.</i><br /><br />Notorious variability in the presentation of mitochondrial disease in the infant and young child complicates its clinical diagnosis. Mitochondrial disease is not a single entity but, rather, a heterogeneous group of disorders characterized by impaired energy production due to genetically based oxidative phosphorylation dysfunction. Together, these disorders constitute the most common neurometabolic disease of childhood with an estimated minimal risk of developing mitochondrial disease of 1 in 5000. Diagnostic difficulty results from not only the variable and often nonspecific presentation of these disorders but also from the absence of a reliable biomarker specific for the screening or diagnosis of mitochondrial disease. A simplified and standardized approach to facilitate the clinical recognition of mitochondrial disease by primary physicians is needed. With this article we aimed to improve the clinical recognition of mitochondrial disease by primary care providers and empower the generalist to initiate appropriate baseline diagnostic testing before determining the need for specialist referral. This is particularly important in light of the international shortage of metabolism specialists to comprehensively evaluate this large and complex disease population. It is hoped that greater familiarity among primary care physicians with the protean manifestations of mitochondrial disease will facilitate the proper diagnosis and management of this growing cohort of pediatric patients who present across all specialties. Mitochondrial disease: a practical approach for primary care physicians. RH Haas S Parikh MJ Falk RP Saneto NI Wolf N Darin BH Cohen doi:10.1542/peds.2007-0391 Pediatrics, Vol. 120, No. 6. (December 2007), pp. 1326-1333. 2008-04-17T14:19:15-00:00 2007 Pediatrics 1098-4275 120 6 1326 1333 clinical disease methodspaper mitochondria review http://www.citeulike.org/user/raiyar/article/2548279 <i>Nature (16 March 2008)</i> Variations in DNA elucidate molecular networks that cause disease Yanqing Chen Jun Zhu Pek Lum Xia Yang Shirly Pinto Douglas Macneil Chunsheng Zhang John Lamb Stephen Edwards Solveig Sieberts Amy Leonardson Lawrence Castellini Susanna Wang Marie-France Champy Bin Zhang Valur Emilsson Sudheer Doss Anatole Ghazalpour Steve Horvath Thomas Drake Aldons Lusis Eric Schadt doi:10.1038/nature06757 Nature (16 March 2008) 2008-03-18T04:25:40-00:00 2008 Nature 0028-0836 Nature Publishing Group disease expression genetic human methodspaper model network qtl systems http://www.citeulike.org/user/raiyar/article/752821 <i>Nucleic Acids Res, Vol. 34, No. Database issue. (1 January 2006)</i><br /><br />In recent years, the Munich Information Center for Protein Sequences (MIPS) yeast protein-protein interaction (PPI) dataset has been used in numerous analyses of protein networks and has been called a gold standard because of its quality and comprehensiveness [H. Yu, N. M. Luscombe, H. X. Lu, X. Zhu, Y. Xia, J. D. Han, N. Bertin, S. Chung, M. Vidal and M. Gerstein (2004) Genome Res., 14, 1107-1118]. MPact and the yeast protein localization catalog provide information related to the proximity of proteins in yeast. Beside the integration of high-throughput data, information about experimental evidence for PPIs in the literature was compiled by experts adding up to 4300 distinct PPIs connecting 1500 proteins in yeast. As the interaction data is a complementary part of CYGD, interactive mapping of data on other integrated data types such as the functional classification catalog [A. Ruepp, A. Zollner, D. Maier, K. Albermann, J. Hani, M. Mokrejs, I. Tetko, U. Güldener, G. Mannhaupt, M. Münsterkötter and H. W. Mewes (2004) Nucleic Acids Res., 32, 5539-5545] is possible. A survey of signaling proteins and comparison with pathway data from KEGG demonstrates that based on these manually annotated data only an extensive overview of the complexity of this functional network can be obtained in yeast. The implementation of a web-based PPI-analysis tool allows analysis and visualization of protein interaction networks and facilitates integration of our curated data with high-throughput datasets. The complete dataset as well as user-defined sub-networks can be retrieved easily in the standardized PSI-MI format. The resource can be accessed through http://mips.gsf.de/genre/proj/mpact. MPact: the MIPS protein interaction resource on yeast. U Güldener M Münsterkötter M Oesterheld P Pagel A Ruepp HW Mewes V Stümpflen Nucleic Acids Res, Vol. 34, No. Database issue. (1 January 2006) 2006-07-11T12:45:35-00:00 2006 Nucleic Acids Res 1362-4962 34 Database issue db interaction methodspaper yeast http://www.citeulike.org/user/raiyar/article/2667592 <i>Nature biotechnology, Vol. 21, No. 3. (March 2003), pp. 287-293.</i><br /><br />The control of intricate networks within eukaryotic cells relies on differential compartmentalization of proteins. We have developed a method that allows rapid identification of novel proteins compartmentalized in mitochondria by screening large-scale cDNA libraries. The principle is based on reconstitution of split-enhanced green fluorescent protein (EGFP) by protein splicing of DnaE derived from Synechocystis sp. PCC6803. The cDNA libraries are expressed in mammalian cells following infection with retrovirus. If a test protein contains a functional mitochondrial targeting signal (MTS), it translocates into the mitochondrial matrix, where EGFP is then formed by protein splicing. The cells harboring this reconstituted EGFP are screened rapidly by fluorescence-activated cell sorting, and the cDNAs are isolated and identified from the cells. The analysis of 258 cDNAs revealed various MTSs, among which we identified new transcripts corresponding to mitochondrial proteins. This method should provide a means to map proteins distributed within intracellular organelles in a broad range of different tissues and disease states. A genetic approach to identifying mitochondrial proteins. T Ozawa Y Sako M Sato T Kitamura Y Umezawa doi:10.1038/nbt791 Nature biotechnology, Vol. 21, No. 3. (March 2003), pp. 287-293. 2008-04-14T12:49:55-00:00 2003 Nature biotechnology 1087-0156 21 3 287 293 genetic ht methodspaper mitochondria parts-list technique http://www.citeulike.org/user/raiyar/article/2175731 <i>Cell, Vol. 131, No. 7. (28 December 2007), pp. 1354-1365.</i><br /><br />Summary The environment significantly influences the dynamic expression and assembly of all components encoded in the genome of an organism into functional biological networks. We have constructed a model for this process in Halobacterium salinarum NRC-1 through the data-driven discovery of regulatory and functional interrelationships among ~80% of its genes and key abiotic factors in its hypersaline environment. Using relative changes in 72 transcription factors and 9 environmental factors (EFs) this model accurately predicts dynamic transcriptional responses of all these genes in 147 newly collected experiments representing completely novel genetic backgrounds and environments--suggesting a remarkable degree of network completeness. Using this model we have constructed and tested hypotheses critical to this organism's interaction with its changing hypersaline environment. This study supports the claim that the high degree of connectivity within biological and EF networks will enable the construction of similar models for any organism from relatively modest numbers of experiments. A Predictive Model for Transcriptional Control of Physiology in a Free Living Cell Richard Bonneau Marc Facciotti David Reiss Amy Schmid Min Pan Amardeep Kaur Vesteinn Thorsson Paul Shannon Michael Johnson Christopher Bare William Longabaugh Madhavi Vuthoori Kenia Whitehead Aviv Madar Lena Suzuki Tetsuya Mori Dong-Eun Chang Jocelyne Diruggiero Carl Johnson Leroy Hood Nitin Baliga doi:10.1016/j.cell.2007.10.053 Cell, Vol. 131, No. 7. (28 December 2007), pp. 1354-1365. 2007-12-27T20:18:55-00:00 2007 Cell 131 7 1354 1365 methodspaper model network prediction http://www.citeulike.org/user/raiyar/article/2658116 <i>Lab on a chip, Vol. 8, No. 2. (February 2008), pp. 198-220.</i><br /><br />Droplet-based microfluidic systems have been shown to be compatible with many chemical and biological reagents and capable of performing a variety of "digital fluidic" operations that can be rendered programmable and reconfigurable. This platform has dimensional scaling benefits that have enabled controlled and rapid mixing of fluids in the droplet reactors, resulting in decreased reaction times. This, coupled with the precise generation and repeatability of droplet operations, has made the droplet-based microfluidic system a potent high throughput platform for biomedical research and applications. In addition to being used as microreactors ranging from the nano- to femtoliter range; droplet-based systems have also been used to directly synthesize particles and encapsulate many biological entities for biomedicine and biotechnology applications. This review will focus on the various droplet operations, as well as the numerous applications of the system. Due to advantages unique to droplet-based systems, this technology has the potential to provide novel solutions to today's biomedical engineering challenges for advanced diagnostics and therapeutics. Droplet microfluidics. SY Teh R Lin LH Hung AP Lee doi:10.1039/b715524g Lab on a chip, Vol. 8, No. 2. (February 2008), pp. 198-220. 2008-04-11T15:09:22-00:00 2008 Lab on a chip 1473-0197 8 2 198 220 methodspaper technique tool http://www.citeulike.org/user/raiyar/article/2409960 <i>J Proteome Res, Vol. 7, No. 1. (January 2008), pp. 51-61.</i><br /><br />Over the past decade, a series of experimental strategies for mass spectrometry based quantitative proteomics and corresponding computational methodology for the processing of the resulting data have been generated. We provide here an overview of the main quantification principles and available software solutions for the analysis of data generated by liquid chromatography coupled to mass spectrometry (LC-MS). Three conceptually different methods to perform quantitative LC-MS experiments have been introduced. In the first, quantification is achieved by spectral counting, in the second via differential stable isotopic labeling, and in the third by using the ion current in label-free LC-MS measurements. We discuss here advantages and challenges of each quantification approach and assess available software solutions with respect to their instrument compatibility and processing functionality. This review therefore serves as a starting point for researchers to choose an appropriate software solution for quantitative proteomic experiments based on their experimental and analytical requirements. An assessment of software solutions for the analysis of mass spectrometry based quantitative proteomics data. LN Mueller MY Brusniak DR Mani R Aebersold doi:10.1021/pr700758r J Proteome Res, Vol. 7, No. 1. (January 2008), pp. 51-61. 2008-02-22T02:58:17-00:00 2008 J Proteome Res 1535-3893 7 1 51 61 analysis bioinformatics methodspaper proteomics review http://www.citeulike.org/user/raiyar/article/306145 <i>Science, Vol. 302, No. 5644. (17 October 2003), pp. 449-453.</i><br /><br />We have developed an approach using Bayesian networks to predict protein-protein interactions genome-wide in yeast. Our method naturally weights and combines into reliable predictions genomic features only weakly associated with interaction (e.g., messenger RNAcoexpression, coessentiality, and colocalization). In addition to de novo predictions, it can integrate often noisy, experimental interaction data sets. We observe that at given levels of sensitivity, our predictions are more accurate than the existing high-throughput experimental data sets. We validate our predictions with TAP (tandem affinity purification) tagging experiments. Our analysis, which gives a comprehensive view of yeast interactions, is available at genecensus.org/intint. A Bayesian networks approach for predicting protein-protein interactions from genomic data. R Jansen H Yu D Greenbaum Y Kluger NJ Krogan S Chung A Emili M Snyder JF Greenblatt M Gerstein doi:10.1126/science.1087361 Science, Vol. 302, No. 5644. (17 October 2003), pp. 449-453. 2005-08-29T17:53:27-00:00 2003 Science 1095-9203 302 5644 449 453 genomics integration interaction methodspaper prediction http://www.citeulike.org/user/raiyar/article/2102204 <i>Nucl. Acids Res. (12 December 2007), gkm882.</i><br /><br />KEGG (http://www.genome.jp/kegg/) is a database of biological systems that integrates genomic, chemical and systemic functional information. KEGG provides a reference knowledge base for linking genomes to life through the process of PATHWAY mapping, which is to map, for example, a genomic or transcriptomic content of genes to KEGG reference pathways to infer systemic behaviors of the cell or the organism. In addition, KEGG provides a reference knowledge base for linking genomes to the environment, such as for the analysis of drug-target relationships, through the process of BRITE mapping. KEGG BRITE is an ontology database representing functional hierarchies of various biological objects, including molecules, cells, organisms, diseases and drugs, as well as relationships among them. KEGG PATHWAY is now supplemented with a new global map of metabolic pathways, which is essentially a combined map of about 120 existing pathway maps. In addition, smaller pathway modules are defined and stored in KEGG MODULE that also contains other functional units and complexes. The KEGG resource is being expanded to suit the needs for practical applications. KEGG DRUG contains all approved drugs in the US and Japan, and KEGG DISEASE is a new database linking disease genes, pathways, drugs and diagnostic markers. 10.1093/nar/gkm882 KEGG for linking genomes to life and the environment Minoru Kanehisa Michihiro Araki Susumu Goto Masahiro Hattori Mika Hirakawa Masumi Itoh Toshiaki Katayama Shuichi Kawashima Shujiro Okuda Toshiaki Tokimatsu Yoshihiro Yamanishi doi:10.1093/nar/gkm882 Nucl. Acids Res. (12 December 2007), gkm882. 2007-12-13T06:01:37-00:00 2007 Nucl. Acids Res. gkm882 bioinformatics db genomics interaction metabolic methodspaper prediction systems tool http://www.citeulike.org/user/raiyar/article/1169116 <i>Genome Biology, Vol. 8 (16 March 2007), R39.</i> Reactome: a knowledgebase of biological pathways and processes Imre Vastrik Peter D'Eustachio Esther Schmidt Geeta Joshi-Tope Gopal Gopinath David Croft Bernard de Bono Marc Gillespie Bijay Jassal Suzanna Lewis Lisa Matthews Guanming Wu Ewan Birney Lincoln Stein doi:10.1186/gb-2007-8-3-r39 Genome Biology, Vol. 8 (16 March 2007), R39. 2007-03-17T17:43:21-00:00 2007 Genome Biology 1465-6906 8 R39 bioinformatics db interaction metabolic methodspaper tool http://www.citeulike.org/user/raiyar/article/963155 <i>Gene, Vol. 156, No. 1. (14 April 1995), pp. 119-122.</i><br /><br />An expression system for Saccharomyces cerevisiae (Sc) has been developed which, depending on the chosen vector, allows the constitutive expression of proteins at different levels over a range of three orders of magnitude and in different genetic backgrounds. The expression system is comprised of cassettes composed of a weak CYC1 promoter, the ADH promoter or the stronger TEF and GPD promoters, flanked by a cloning array and the CYC1 terminator. The multiple cloning array based on pBIISK (Stratagene) provides six to nine unique restriction sites, which facilitates the cloning of genes and allows for the directed cloning of cDNAs by the widely used ZAP system (Stratagene). Expression cassettes were placed into both the centromeric and 2 mu plasmids of the pRS series [Sikorski and Hieter, Genetics 122 (1989) 19-27; Christianson et al., Gene 110 (1992) 119-122] containing HIS3, TRP1, LEU2 or URA3 markers. The 32 expression vectors created by this strategy provide a powerful tool for the convenient cloning and the controlled expression of genes or cDNAs in nearly every genetic background of the currently used Sc strains. Yeast vectors for the controlled expression of heterologous proteins in different genetic backgrounds. D Mumberg R Müller M Funk Gene, Vol. 156, No. 1. (14 April 1995), pp. 119-122. 2006-11-27T10:51:12-00:00 1995 Gene 0378-1119 156 1 119 122 technique tool vector yeast http://www.citeulike.org/user/raiyar/article/2644224 <i>Science, Vol. 283, No. 5407. (5 March 1999), pp. 1476-1481.</i><br /><br />10.1126/science.283.5407.1476 Mitochondrial Evolution Michael Gray Gertraud Burger Franz Lang doi:10.1126/science.283.5407.1476 Science, Vol. 283, No. 5407. (5 March 1999), pp. 1476-1481. 2008-04-09T10:17:37-00:00 1999 Science 283 5407 1476 1481 basis evolution mtdna projmt review http://www.citeulike.org/user/raiyar/article/2622824 <i>Rejuvenation research, Vol. 9, No. 4. (2006), pp. 455-469.</i><br /><br />Artificial transfer of mitochondrial genes to the nucleus has implications for the understanding of mitochondrial function, evolution, and human health. Therefore, we created nuclear compatible versions of human subunit a (A6) of ATP synthase, linked to a mitochondrial targeting signal. Expression and targeting of human nuclear subunit a were compared to subunit a of Chlamydomonas reinhardtii, which naturally occurs in the nucleus. Algal subunit a was targeted to mitochondria more efficiently than human nuclear subunit a variants. However, there was no evidence of improved mitochondrial function in cultured cells; on the contrary, long-term expression of algal subunit a was associated with poor survival and intolerance of growth conditions that demand heavy reliance on oxidative phosphorylation. Analysis of enriched mitochondrial membrane fractions on native gels revealed a high-molecular- weight complex containing FLAG-tagged subunit a; however, this complex did not colocalize with ATP synthase. Thus, there was no evidence of assembly of algal subunit a into holoenzyme, nor did human nuclear subunit a colocalize with ATP synthase holoenzyme. In conclusion, obstacles remain to functional expression of mitochondrial genes transferred to the nucleus. Expression of algal nuclear ATP synthase subunit 6 in human cells results in protein targeting to mitochondria but no assembly into ATP synthase. M Bokori-Brown IJ Holt doi:10.1089/rej.2006.9.455 Rejuvenation research, Vol. 9, No. 4. (2006), pp. 455-469. 2008-04-02T09:35:34-00:00 2006 Rejuvenation research 1549-1684 9 4 455 469 allotopic atp6 chlamydomonas human mitochondria mtdna projmt sgtcnih http://www.citeulike.org/user/raiyar/article/2620197 <i>Expert Rev Proteomics, Vol. 2, No. 4. (August 2005), pp. 541-551.</i><br /><br />Mitochondria are essential organelles for cellular homeostasis. A variety of pathologies including cancer, myopathies, diabetes, obesity, aging and neurodegenerative diseases are linked to mitochondrial dysfunction. Therefore, mapping the different components of mitochondria is of particular interest to gain further understanding of such diseases. In recent years, proteomics-based approaches have been developed in attempts to determine the complete set of mitochondrial proteins in yeast, plants and mammals. In addition, proteomics-based methods have been applied not only to the analysis of protein function in the organelle, but also to identify biomarkers for diagnosis and therapeutic targets of specific pathologies associated with mitochondria. Altogether, it is becoming clear that proteomics is a powerful tool not only to identify currently unknown components of the mitochondrion, but also to study the different roles of the organelle in cellular homeostasis. Building the mitochondrial proteome. S Da Cruz PA Parone JC Martinou doi:10.1586/14789450.2.4.541 Expert Rev Proteomics, Vol. 2, No. 4. (August 2005), pp. 541-551. 2008-04-01T14:38:12-00:00 2005 Expert Rev Proteomics 1744-8387 2 4 541 551 methodspaper mitochondria proteomics technique http://www.citeulike.org/user/raiyar/article/942053 <i>Methods, Vol. 35, No. 3. (March 2005), pp. 248-255.</i><br /><br />Multidimensional liquid chromatography techniques have been coupled to tandem mass spectrometry to provide a robust method to identify proteins in complex mixtures. Data acquisition is interfaced directly with search algorithms for identification through cross-correlation with databases. This review describes the most recent advances in methodologies for protein identification by mass spectrometry and describes the limitations of the application of the technologies. Protein identification using 2D-LC-MS/MS Claire Delahunty Yates doi:10.1016/j.ymeth.2004.08.016 Methods, Vol. 35, No. 3. (March 2005), pp. 248-255. 2006-11-13T19:35:28-00:00 2005 Methods 35 3 248 255 basis methodspaper proteomics technique