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1.  BioHackathon series in 2011 and 2012: penetration of ontology and linked data in life science domains 
Katayama, Toshiaki | Wilkinson, Mark D | Aoki-Kinoshita, Kiyoko F | Kawashima, Shuichi | Yamamoto, Yasunori | Yamaguchi, Atsuko | Okamoto, Shinobu | Kawano, Shin | Kim, Jin-Dong | Wang, Yue | Wu, Hongyan | Kano, Yoshinobu | Ono, Hiromasa | Bono, Hidemasa | Kocbek, Simon | Aerts, Jan | Akune, Yukie | Antezana, Erick | Arakawa, Kazuharu | Aranda, Bruno | Baran, Joachim | Bolleman, Jerven | Bonnal, Raoul JP | Buttigieg, Pier Luigi | Campbell, Matthew P | Chen, Yi-an | Chiba, Hirokazu | Cock, Peter JA | Cohen, K Bretonnel | Constantin, Alexandru | Duck, Geraint | Dumontier, Michel | Fujisawa, Takatomo | Fujiwara, Toyofumi | Goto, Naohisa | Hoehndorf, Robert | Igarashi, Yoshinobu | Itaya, Hidetoshi | Ito, Maori | Iwasaki, Wataru | Kalaš, Matúš | Katoda, Takeo | Kim, Taehong | Kokubu, Anna | Komiyama, Yusuke | Kotera, Masaaki | Laibe, Camille | Lapp, Hilmar | Lütteke, Thomas | Marshall, M Scott | Mori, Takaaki | Mori, Hiroshi | Morita, Mizuki | Murakami, Katsuhiko | Nakao, Mitsuteru | Narimatsu, Hisashi | Nishide, Hiroyo | Nishimura, Yosuke | Nystrom-Persson, Johan | Ogishima, Soichi | Okamura, Yasunobu | Okuda, Shujiro | Oshita, Kazuki | Packer, Nicki H | Prins, Pjotr | Ranzinger, Rene | Rocca-Serra, Philippe | Sansone, Susanna | Sawaki, Hiromichi | Shin, Sung-Ho | Splendiani, Andrea | Strozzi, Francesco | Tadaka, Shu | Toukach, Philip | Uchiyama, Ikuo | Umezaki, Masahito | Vos, Rutger | Whetzel, Patricia L | Yamada, Issaku | Yamasaki, Chisato | Yamashita, Riu | York, William S | Zmasek, Christian M | Kawamoto, Shoko | Takagi, Toshihisa
The application of semantic technologies to the integration of biological data and the interoperability of bioinformatics analysis and visualization tools has been the common theme of a series of annual BioHackathons hosted in Japan for the past five years. Here we provide a review of the activities and outcomes from the BioHackathons held in 2011 in Kyoto and 2012 in Toyama. In order to efficiently implement semantic technologies in the life sciences, participants formed various sub-groups and worked on the following topics: Resource Description Framework (RDF) models for specific domains, text mining of the literature, ontology development, essential metadata for biological databases, platforms to enable efficient Semantic Web technology development and interoperability, and the development of applications for Semantic Web data. In this review, we briefly introduce the themes covered by these sub-groups. The observations made, conclusions drawn, and software development projects that emerged from these activities are discussed.
doi:10.1186/2041-1480-5-5
PMCID: PMC3978116  PMID: 24495517
BioHackathon; Bioinformatics; Semantic Web; Web services; Ontology; Visualization; Knowledge representation; Databases; Semantic interoperability; Data models; Data sharing; Data integration
3.  The 3rd DBCLS BioHackathon: improving life science data integration with Semantic Web technologies 
Background
BioHackathon 2010 was the third in a series of meetings hosted by the Database Center for Life Sciences (DBCLS) in Tokyo, Japan. The overall goal of the BioHackathon series is to improve the quality and accessibility of life science research data on the Web by bringing together representatives from public databases, analytical tool providers, and cyber-infrastructure researchers to jointly tackle important challenges in the area of in silico biological research.
Results
The theme of BioHackathon 2010 was the 'Semantic Web', and all attendees gathered with the shared goal of producing Semantic Web data from their respective resources, and/or consuming or interacting those data using their tools and interfaces. We discussed on topics including guidelines for designing semantic data and interoperability of resources. We consequently developed tools and clients for analysis and visualization.
Conclusion
We provide a meeting report from BioHackathon 2010, in which we describe the discussions, decisions, and breakthroughs made as we moved towards compliance with Semantic Web technologies - from source provider, through middleware, to the end-consumer.
doi:10.1186/2041-1480-4-6
PMCID: PMC3598643  PMID: 23398680
BioHackathon; Open source; Software; Semantic Web; Databases; Data integration; Data visualization; Web services; Interfaces
4.  H-InvDB in 2013: an omics study platform for human functional gene and transcript discovery 
Nucleic Acids Research  2012;41(Database issue):D915-D919.
H-InvDB (http://www.h-invitational.jp/) is a comprehensive human gene database started in 2004. In the latest version, H-InvDB 8.0, a total of 244 709 human complementary DNA was mapped onto the hg19 reference genome and 43 829 gene loci, including nonprotein-coding ones, were identified. Of these loci, 35 631 were identified as potential protein-coding genes, and 22 898 of these were identical to known genes. In our analysis, 19 309 annotated genes were specific to H-InvDB and not found in RefSeq and Ensembl. In fact, 233 genes of the 19 309 turned out to have protein functions in this version of H-InvDB; they were annotated as unknown protein functions in the previous version. Furthermore, 11 genes were identified as known Mendelian disorder genes. It is advantageous that many biologically functional genes are hidden in the H-InvDB unique genes. As large-scale proteomic projects have been conducted to elucidate the functions of all human proteins, we have enhanced the proteomic information with an advanced protein view and new subdatabase of protein complexes (Protein Complex Database with quality index). We propose that H-InvDB is an important resource for finding novel candidate targets for medical care and drug development.
doi:10.1093/nar/gks1245
PMCID: PMC3531145  PMID: 23197657
5.  Comparative Genome Analysis of Three Eukaryotic Parasites with Differing Abilities To Transform Leukocytes Reveals Key Mediators of Theileria-Induced Leukocyte Transformation 
mBio  2012;3(5):e00204-12.
ABSTRACT
We sequenced the genome of Theileria orientalis, a tick-borne apicomplexan protozoan parasite of cattle. The focus of this study was a comparative genome analysis of T. orientalis relative to other highly pathogenic Theileria species, T. parva and T. annulata. T. parva and T. annulata induce transformation of infected cells of lymphocyte or macrophage/monocyte lineages; in contrast, T. orientalis does not induce uncontrolled proliferation of infected leukocytes and multiplies predominantly within infected erythrocytes. While synteny across homologous chromosomes of the three Theileria species was found to be well conserved overall, subtelomeric structures were found to differ substantially, as T. orientalis lacks the large tandemly arrayed subtelomere-encoded variable secreted protein-encoding gene family. Moreover, expansion of particular gene families by gene duplication was found in the genomes of the two transforming Theileria species, most notably, the TashAT/TpHN and Tar/Tpr gene families. Gene families that are present only in T. parva and T. annulata and not in T. orientalis, Babesia bovis, or Plasmodium were also identified. Identification of differences between the genome sequences of Theileria species with different abilities to transform and immortalize bovine leukocytes will provide insight into proteins and mechanisms that have evolved to induce and regulate this process. The T. orientalis genome database is available at http://totdb.czc.hokudai.ac.jp/.
IMPORTANCE
Cancer-like growth of leukocytes infected with malignant Theileria parasites is a unique cellular event, as it involves the transformation and immortalization of one eukaryotic cell by another. In this study, we sequenced the whole genome of a nontransforming Theileria species, Theileria orientalis, and compared it to the published sequences representative of two malignant, transforming species, T. parva and T. annulata. The genome-wide comparison of these parasite species highlights significant genetic diversity that may be associated with evolution of the mechanism(s) deployed by an intracellular eukaryotic parasite to transform its host cell.
doi:10.1128/mBio.00204-12
PMCID: PMC3445966  PMID: 22951932
6.  The 2nd DBCLS BioHackathon: interoperable bioinformatics Web services for integrated applications 
Background
The interaction between biological researchers and the bioinformatics tools they use is still hampered by incomplete interoperability between such tools. To ensure interoperability initiatives are effectively deployed, end-user applications need to be aware of, and support, best practices and standards. Here, we report on an initiative in which software developers and genome biologists came together to explore and raise awareness of these issues: BioHackathon 2009.
Results
Developers in attendance came from diverse backgrounds, with experts in Web services, workflow tools, text mining and visualization. Genome biologists provided expertise and exemplar data from the domains of sequence and pathway analysis and glyco-informatics. One goal of the meeting was to evaluate the ability to address real world use cases in these domains using the tools that the developers represented. This resulted in i) a workflow to annotate 100,000 sequences from an invertebrate species; ii) an integrated system for analysis of the transcription factor binding sites (TFBSs) enriched based on differential gene expression data obtained from a microarray experiment; iii) a workflow to enumerate putative physical protein interactions among enzymes in a metabolic pathway using protein structure data; iv) a workflow to analyze glyco-gene-related diseases by searching for human homologs of glyco-genes in other species, such as fruit flies, and retrieving their phenotype-annotated SNPs.
Conclusions
Beyond deriving prototype solutions for each use-case, a second major purpose of the BioHackathon was to highlight areas of insufficiency. We discuss the issues raised by our exploration of the problem/solution space, concluding that there are still problems with the way Web services are modeled and annotated, including: i) the absence of several useful data or analysis functions in the Web service "space"; ii) the lack of documentation of methods; iii) lack of compliance with the SOAP/WSDL specification among and between various programming-language libraries; and iv) incompatibility between various bioinformatics data formats. Although it was still difficult to solve real world problems posed to the developers by the biological researchers in attendance because of these problems, we note the promise of addressing these issues within a semantic framework.
doi:10.1186/2041-1480-2-4
PMCID: PMC3170566  PMID: 21806842
7.  Towards BioDBcore: a community-defined information specification for biological databases 
The present article proposes the adoption of a community-defined, uniform, generic description of the core attributes of biological databases, BioDBCore. The goals of these attributes are to provide a general overview of the database landscape, to encourage consistency and interoperability between resources; and to promote the use of semantic and syntactic standards. BioDBCore will make it easier for users to evaluate the scope and relevance of available resources. This new resource will increase the collective impact of the information present in biological databases.
doi:10.1093/database/baq027
PMCID: PMC3017395  PMID: 21205783
8.  Towards BioDBcore: a community-defined information specification for biological databases 
Nucleic Acids Research  2010;39(Database issue):D7-D10.
The present article proposes the adoption of a community-defined, uniform, generic description of the core attributes of biological databases, BioDBCore. The goals of these attributes are to provide a general overview of the database landscape, to encourage consistency and interoperability between resources and to promote the use of semantic and syntactic standards. BioDBCore will make it easier for users to evaluate the scope and relevance of available resources. This new resource will increase the collective impact of the information present in biological databases.
doi:10.1093/nar/gkq1173
PMCID: PMC3013734  PMID: 21097465
9.  CIPRO 2.5: Ciona intestinalis protein database, a unique integrated repository of large-scale omics data, bioinformatic analyses and curated annotation, with user rating and reviewing functionality 
Nucleic Acids Research  2010;39(Database issue):D807-D814.
The Ciona intestinalis protein database (CIPRO) is an integrated protein database for the tunicate species C. intestinalis. The database is unique in two respects: first, because of its phylogenetic position, Ciona is suitable model for understanding vertebrate evolution; and second, the database includes original large-scale transcriptomic and proteomic data. Ciona intestinalis has also been a favorite of developmental biologists. Therefore, large amounts of data exist on its development and morphology, along with a recent genome sequence and gene expression data. The CIPRO database is aimed at collecting those published data as well as providing unique information from unpublished experimental data, such as 3D expression profiling, 2D-PAGE and mass spectrometry-based large-scale analyses at various developmental stages, curated annotation data and various bioinformatic data, to facilitate research in diverse areas, including developmental, comparative and evolutionary biology. For medical and evolutionary research, homologs in humans and major model organisms are intentionally included. The current database is based on a recently developed KH model containing 36 034 unique sequences, but for higher usability it covers 89 683 all known and predicted proteins from all gene models for this species. Of these sequences, more than 10 000 proteins have been manually annotated. Furthermore, to establish a community-supported protein database, these annotations are open to evaluation by users through the CIPRO website. CIPRO 2.5 is freely accessible at http://cipro.ibio.jp/2.5.
doi:10.1093/nar/gkq1144
PMCID: PMC3013717  PMID: 21071393
11.  H-InvDB in 2009: extended database and data mining resources for human genes and transcripts 
Nucleic Acids Research  2009;38(Database issue):D626-D632.
We report the extended database and data mining resources newly released in the H-Invitational Database (H-InvDB; http://www.h-invitational.jp/). H-InvDB is a comprehensive annotation resource of human genes and transcripts, and consists of two main views and six sub-databases. The latest release of H-InvDB (release 6.2) provides the annotation for 219 765 human transcripts in 43 159 human gene clusters based on human full-length cDNAs and mRNAs. H-InvDB now provides several new annotation features, such as mapping of microarray probes, new gene models, relation to known ncRNAs and information from the Glycogene database. H-InvDB also provides useful data mining resources—‘Navigation search’, ‘H-InvDB Enrichment Analysis Tool (HEAT)’ and web service APIs. ‘Navigation search’ is an extended search system that enables complicated searches by combining 16 different search options. HEAT is a data mining tool for automatically identifying features specific to a given human gene set. HEAT searches for H-InvDB annotations that are significantly enriched in a user-defined gene set, as compared with the entire H-InvDB representative transcripts. H-InvDB now has web service APIs of SOAP and REST to allow the use of H-InvDB data in programs, providing the users extended data accessibility.
doi:10.1093/nar/gkp1020
PMCID: PMC2808976  PMID: 19933760
12.  VarySysDB: a human genetic polymorphism database based on all H-InvDB transcripts 
Nucleic Acids Research  2008;37(Database issue):D810-D815.
Creation of a vast variety of proteins is accomplished by genetic variation and a variety of alternative splicing transcripts. Currently, however, the abundant available data on genetic variation and the transcriptome are stored independently and in a dispersed fashion. In order to provide a research resource regarding the effects of human genetic polymorphism on various transcripts, we developed VarySysDB, a genetic polymorphism database based on 187 156 extensively annotated matured mRNA transcripts from 36 073 loci provided by H-InvDB. VarySysDB offers information encompassing published human genetic polymorphisms for each of these transcripts separately. This allows comparisons of effects derived from a polymorphism on different transcripts. The published information we analyzed includes single nucleotide polymorphisms and deletion–insertion polymorphisms from dbSNP, copy number variations from Database of Genomic Variants, short tandem repeats and single amino acid repeats from H-InvDB and linkage disequilibrium regions from D-HaploDB. The information can be searched and retrieved by features, functions and effects of polymorphisms, as well as by keywords. VarySysDB combines two kinds of viewers, GBrowse and Sequence View, to facilitate understanding of the positional relationship among polymorphisms, genome, transcripts, loci and functional domains. We expect that VarySysDB will yield useful information on polymorphisms affecting gene expression and phenotypes. VarySysDB is available at http://h-invitational.jp/varygene/.
doi:10.1093/nar/gkn798
PMCID: PMC2686441  PMID: 18953038
13.  Evola: Ortholog database of all human genes in H-InvDB with manual curation of phylogenetic trees 
Nucleic Acids Research  2007;36(Database issue):D787-D792.
Orthologs are genes in different species that evolved from a common ancestral gene by speciation. Currently, with the rapid growth of transcriptome data of various species, more reliable orthology information is prerequisite for further studies. However, detection of orthologs could be erroneous if pairwise distance-based methods, such as reciprocal BLAST searches, are utilized. Thus, as a sub-database of H-InvDB, an integrated database of annotated human genes (http://h-invitational.jp/), we constructed a fully curated database of evolutionary features of human genes, called ‘Evola’. In the process of the ortholog detection, computational analysis based on conserved genome synteny and transcript sequence similarity was followed by manual curation by researchers examining phylogenetic trees. In total, 18 968 human genes have orthologs among 11 vertebrates (chimpanzee, mouse, cow, chicken, zebrafish, etc.), either computationally detected or manually curated orthologs. Evola provides amino acid sequence alignments and phylogenetic trees of orthologs and homologs. In ‘dN/dS view’, natural selection on genes can be analyzed between human and other species. In ‘Locus maps’, all transcript variants and their exon/intron structures can be compared among orthologous gene loci. We expect the Evola to serve as a comprehensive and reliable database to be utilized in comparative analyses for obtaining new knowledge about human genes. Evola is available at http://www.h-invitational.jp/evola/.
doi:10.1093/nar/gkm878
PMCID: PMC2238928  PMID: 17982176
14.  TACT: Transcriptome Auto-annotation Conducting Tool of H-InvDB 
Nucleic Acids Research  2006;34(Web Server issue):W345-W349.
Transcriptome Auto-annotation Conducting Tool (TACT) is a newly developed web-based automated tool for conducting functional annotation of transcripts by the integration of sequence similarity searches and functional motif predictions. We developed the TACT system by integrating two kinds of similarity searches, FASTY and BLASTX, against protein sequence databases, UniProtKB (Swiss-Prot/TrEMBL) and RefSeq, and a unified motif prediction program, InterProScan, into the ORF-prediction pipeline originally designed for the ‘H-Invitational’ human transcriptome annotation project. This system successively applies these constituent programs to an mRNA sequence in order to predict the most plausible ORF and the function of the protein encoded. In this study, we applied the TACT system to 19 574 non-redundant human transcripts registered in H-InvDB and evaluated its predictive power by the degree of agreement with human-curated functional annotation in H-InvDB. As a result, the TACT system could assign functional description to 12 559 transcripts (64.2%), the remainder being hypothetical proteins. Furthermore, the overall agreement of functional annotation with H-InvDB, including those transcripts annotated as hypothetical proteins, was 83.9% (16 432/19 574). These results show that the TACT system is useful for functional annotation and that the prediction of ORFs and protein functions is highly accurate and close to the results of human curation. TACT is freely available at .
doi:10.1093/nar/gkl283
PMCID: PMC1538819  PMID: 16845023
15.  Integrative Annotation of 21,037 Human Genes Validated by Full-Length cDNA Clones 
Imanishi, Tadashi | Itoh, Takeshi | Suzuki, Yutaka | O'Donovan, Claire | Fukuchi, Satoshi | Koyanagi, Kanako O | Barrero, Roberto A | Tamura, Takuro | Yamaguchi-Kabata, Yumi | Tanino, Motohiko | Yura, Kei | Miyazaki, Satoru | Ikeo, Kazuho | Homma, Keiichi | Kasprzyk, Arek | Nishikawa, Tetsuo | Hirakawa, Mika | Thierry-Mieg, Jean | Thierry-Mieg, Danielle | Ashurst, Jennifer | Jia, Libin | Nakao, Mitsuteru | Thomas, Michael A | Mulder, Nicola | Karavidopoulou, Youla | Jin, Lihua | Kim, Sangsoo | Yasuda, Tomohiro | Lenhard, Boris | Eveno, Eric | Suzuki, Yoshiyuki | Yamasaki, Chisato | Takeda, Jun-ichi | Gough, Craig | Hilton, Phillip | Fujii, Yasuyuki | Sakai, Hiroaki | Tanaka, Susumu | Amid, Clara | Bellgard, Matthew | de Fatima Bonaldo, Maria | Bono, Hidemasa | Bromberg, Susan K | Brookes, Anthony J | Bruford, Elspeth | Carninci, Piero | Chelala, Claude | Couillault, Christine | de Souza, Sandro J. | Debily, Marie-Anne | Devignes, Marie-Dominique | Dubchak, Inna | Endo, Toshinori | Estreicher, Anne | Eyras, Eduardo | Fukami-Kobayashi, Kaoru | R. Gopinath, Gopal | Graudens, Esther | Hahn, Yoonsoo | Han, Michael | Han, Ze-Guang | Hanada, Kousuke | Hanaoka, Hideki | Harada, Erimi | Hashimoto, Katsuyuki | Hinz, Ursula | Hirai, Momoki | Hishiki, Teruyoshi | Hopkinson, Ian | Imbeaud, Sandrine | Inoko, Hidetoshi | Kanapin, Alexander | Kaneko, Yayoi | Kasukawa, Takeya | Kelso, Janet | Kersey, Paul | Kikuno, Reiko | Kimura, Kouichi | Korn, Bernhard | Kuryshev, Vladimir | Makalowska, Izabela | Makino, Takashi | Mano, Shuhei | Mariage-Samson, Regine | Mashima, Jun | Matsuda, Hideo | Mewes, Hans-Werner | Minoshima, Shinsei | Nagai, Keiichi | Nagasaki, Hideki | Nagata, Naoki | Nigam, Rajni | Ogasawara, Osamu | Ohara, Osamu | Ohtsubo, Masafumi | Okada, Norihiro | Okido, Toshihisa | Oota, Satoshi | Ota, Motonori | Ota, Toshio | Otsuki, Tetsuji | Piatier-Tonneau, Dominique | Poustka, Annemarie | Ren, Shuang-Xi | Saitou, Naruya | Sakai, Katsunaga | Sakamoto, Shigetaka | Sakate, Ryuichi | Schupp, Ingo | Servant, Florence | Sherry, Stephen | Shiba, Rie | Shimizu, Nobuyoshi | Shimoyama, Mary | Simpson, Andrew J | Soares, Bento | Steward, Charles | Suwa, Makiko | Suzuki, Mami | Takahashi, Aiko | Tamiya, Gen | Tanaka, Hiroshi | Taylor, Todd | Terwilliger, Joseph D | Unneberg, Per | Veeramachaneni, Vamsi | Watanabe, Shinya | Wilming, Laurens | Yasuda, Norikazu | Yoo, Hyang-Sook | Stodolsky, Marvin | Makalowski, Wojciech | Go, Mitiko | Nakai, Kenta | Takagi, Toshihisa | Kanehisa, Minoru | Sakaki, Yoshiyuki | Quackenbush, John | Okazaki, Yasushi | Hayashizaki, Yoshihide | Hide, Winston | Chakraborty, Ranajit | Nishikawa, Ken | Sugawara, Hideaki | Tateno, Yoshio | Chen, Zhu | Oishi, Michio | Tonellato, Peter | Apweiler, Rolf | Okubo, Kousaku | Wagner, Lukas | Wiemann, Stefan | Strausberg, Robert L | Isogai, Takao | Auffray, Charles | Nomura, Nobuo | Gojobori, Takashi | Sugano, Sumio
PLoS Biology  2004;2(6):e162.
The human genome sequence defines our inherent biological potential; the realization of the biology encoded therein requires knowledge of the function of each gene. Currently, our knowledge in this area is still limited. Several lines of investigation have been used to elucidate the structure and function of the genes in the human genome. Even so, gene prediction remains a difficult task, as the varieties of transcripts of a gene may vary to a great extent. We thus performed an exhaustive integrative characterization of 41,118 full-length cDNAs that capture the gene transcripts as complete functional cassettes, providing an unequivocal report of structural and functional diversity at the gene level. Our international collaboration has validated 21,037 human gene candidates by analysis of high-quality full-length cDNA clones through curation using unified criteria. This led to the identification of 5,155 new gene candidates. It also manifested the most reliable way to control the quality of the cDNA clones. We have developed a human gene database, called the H-Invitational Database (H-InvDB; http://www.h-invitational.jp/). It provides the following: integrative annotation of human genes, description of gene structures, details of novel alternative splicing isoforms, non-protein-coding RNAs, functional domains, subcellular localizations, metabolic pathways, predictions of protein three-dimensional structure, mapping of known single nucleotide polymorphisms (SNPs), identification of polymorphic microsatellite repeats within human genes, and comparative results with mouse full-length cDNAs. The H-InvDB analysis has shown that up to 4% of the human genome sequence (National Center for Biotechnology Information build 34 assembly) may contain misassembled or missing regions. We found that 6.5% of the human gene candidates (1,377 loci) did not have a good protein-coding open reading frame, of which 296 loci are strong candidates for non-protein-coding RNA genes. In addition, among 72,027 uniquely mapped SNPs and insertions/deletions localized within human genes, 13,215 nonsynonymous SNPs, 315 nonsense SNPs, and 452 indels occurred in coding regions. Together with 25 polymorphic microsatellite repeats present in coding regions, they may alter protein structure, causing phenotypic effects or resulting in disease. The H-InvDB platform represents a substantial contribution to resources needed for the exploration of human biology and pathology.
An international team has systematically validated and annotated just over 21,000 human genes using full-length cDNA, thereby providing a valuable new resource for the human genetics community
doi:10.1371/journal.pbio.0020162
PMCID: PMC393292  PMID: 15103394

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