Abstract
Cassava is a globally important food security and industrial crop produced for food, feed, starch and biofuel. Cassava is drought-tolerant and can grow in poor soils. Roots can be stored in the ground for long periods as part of intact growing plants, allowing flexible harvest times for poor farmers in the tropics. In addition, due to cassava’s inherently high starch content, it is a popular source of carbon for industrial purposes and increasingly biofuel. It is, however, relatively low in nutrients and susceptible to several pests and diseases, including attacks from whitefly, mealybug, green mite, cassava mosaic viruses and cassava brown streak viruses. A number of groups worldwide are working to improve cassava by conventional breeding, by molecular marker-aided breeding, and through the use of transgenic approaches. To facilitate the work of these groups, easy access to up-to-date and integrated information resources are essential to enable knowledge sharing and data mining. Here we review the information resources currently available to breeders and researchers and discuss future directions for the cassava community’s data integration and curation.
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Abbreviations
- AATF:
-
African Agricultural Technology Foundation
- AFLP:
-
Amplified Fragment Length Polymorphism
- CABI:
-
Centre for Agricultural Bioscience International
- CAMBIA:
-
Center for the Application of Molecular Biology to International Agriculture
- CATAS:
-
Chinese Academy of Tropical Agricultural Sciences
- CBSD:
-
Cassava Brown Streak Disease
- CBSV:
-
Cassava Brown Streak Virus
- CGIAR:
-
Consultative Group on International Agricultural Research
- CIAT:
-
Centro Internacional de Agricultura Tropical
- DMS:
-
Data Management System
- DOE JGI:
-
Department of Energy Joint Genome Institute
- EMBRAPA:
-
Empresa Brasileira de Pesquisa Agropecuária
- EST:
-
Expressed Sequence Tag
- ESTIMA:
-
EST Information Management Application
- ETH Zurich:
-
Swiss Federal Institute of Technology Zurich
- FTO:
-
Freedom To Operate
- GCP:
-
Generation Challenge Program
- GEOSHARE:
-
Geospatial Open Source Hosting of Agriculture, Resources and Environmental Data
- GIS:
-
Geographic Information System
- GMS:
-
Geneology Management System
- ICIS:
-
International Crop Information System
- IITA:
-
International Institute of Tropical Agriculture
- IP:
-
Intellectual Property
- NARS:
-
National Agricultural Research Systems
- NCBI:
-
National Center for Biotechnology Information
- NRCRI:
-
National Root Crops Research Institute
- PIPRA:
-
Public Intellectual Property Resource for Agriculture
- PlantTFDB:
-
Plant Transcription Factor Database
- PlnTFDB:
-
Plant Transcription Factor Database
- PMN:
-
Plant Metabolic Network
- QTL:
-
Quantitative Trait Loci
- RAPD:
-
Randomly Amplified Polymorphic DNA
- RFLP:
-
Restriction fragment Length Polymorphism
- RIKEN:
-
Rikagaku Kenkyusho (Institute of Physical and Chemical Research Japan)
- SCCB:
-
Shanghai Center for Cassava Biotechnology Chinese Academy of Sciences
- SINGER:
-
System-wide Information Network for Genetic Resources
- SNP:
-
Single Nucleotide Polymorphism
- SRAP:
-
Sequence-Related Amplified Polymorphism
- SSR:
-
Simple Sequence Repeat
- USDA:
-
United States Department of Agriculture
- WHO:
-
World Health Organization
References
AATF (2011) African agricultural technology foundation http://www.aatf-africa.org/. Cited 30 Sept 2011
Agro-MAPS (2011) Food and Agriculture Organization of the United Nations. http://kids.fao.org/agromaps/. Cited 30 Sept 2011
AgTrials (2011) CGIAR’s Global Agricultural Trial Repository. www.agtrials.org. Cited 30 Sept 2011
Akano AO, Dixon AGO, Mba C, Barrera E, Fregene M (2002) Genetic mapping of a dominant gene conferring resistance to cassava mosaic disease. Theor Appl Genet 105:521–525
Alba R, Phillips A, Mackie S, Gillikin N, Maxwell C, Brune P, Ridley W, Fitzpatrick J, Levine M, Harris S (2010) Improvements to the international life sciences institute crop composition database. J Food Compos Anal 23:741–748
Anderson JV, Horvath DP, Chao WS, Foley ME, Hernandez AG, Thimmapuram J, Liu L, Gong GL, Band M, Kim R, Mikel MA (2007) Characterisation of an EST database for the perennial weed leafy spurge: an important resource for weed biology research. Weed Sci 55:193–203
Balyejusa Kizito E, Rönnberg-Wästljung AC, Egwang T, Gullberg U, Fregene M, Westerbergh A (2007) Quantitative trait loci controlling cyanogenic glucoside and dry matter content in cassava (Manihot esculenta Crantz) roots. Hereditas 144:129–136
BGI and CIAT (2011) BGI and CIAT announce collaboration for large-scale genome sequencing of cassava. www.eurekalert.org/pub_releases/2011-12/bs-bac120511.php. Cited 21 Dec 2011
Blair M, Fregene M, Beebe S, Ceballos H (2007) Marker-assisted breeding in common beans and cassava. Marker-assisted selection: Current status and future perspectives in crops, livestock, forestry and fish. Food and Agriculture Organisation of the United Nations (FAO), Rome, pp 81–115
Bombarely A, Menda N, Tecle IY, Buels RM, Strickler S, Fischer-York T, Pujar A, Leto J, Gosselin J, Mueller LA (2011) The Sol Genomics Network (solgenomics.net): growing tomatoes using Perl. Nucleic Acids Res 39:D1149–D1155
CABI (2011) CAB Direct. http://www.cabdirect.org/. Cited 30 Sept 2011
CAMBIAIP (2011) CAMBIA http://www.cambiaip.org/. Cited 30 Sept 2011
Cassava Curated SSRs (2011) IITA http://bioinformatics.iita.org/cassava_SSRs. Cited 30 Sept 2011
Cassava Genome Database (2011) University of Maryland http://cassava.igs.umaryland.edu/cgi-bin/index.cgi. Cited 30 Sept 2011
Cassava Online Archive (2011) RIKEN http://cassava.psc.riken.jp/index.pl. Cited 30 Sept 2011
Cassava Registry (2011) CIAT and IITA http://istest.ciat.cgiar.org/cassavaregistry/JSPX/home.jspx. Cited 30 Sept 2011
Cassava Trait Ontology (2011) Crop ontology curation tool http://www.cropontology-curationtool.org/. Cited 30 Sept 2011
Castor Bean Genome Database (2011) J. Craig Venter Institute http://castorbean.jcvi.org/index.php. Cited 30 Sept 2011
Ceballos H, Iglesias CA, Perez JC, Dixon AGO (2004) Cassava breeding: opportunities and challenges. Plant Mol Biol 56:503–516
Cenargen (2011) EMBRAPA herbarium http://pragawall.cenargen.embrapa.br/elcen2web/elc2html/elc2bd01a.asp?id=61. Cited 30 Sept 2011
Chan AP, Crabtree J, Zhao Q, Lorenzi H, Orvis J, Puiu D, Melake-Berhan A, Jones KM, Redman J, Chen G, Cahoon EB, Gedil M, Stanke M, Haas BJ, Wortman JR, Fraser-Liggett CM, Ravel J, Rabinowicz PD (2010) Draft genome sequence of the oilseed species Ricinus communis. Nat Biotechnol 28:951–956
Charles AL, Sriroth K, Huang T (2005) Proximate composition, mineral contents, hydrogen cyanide and phytic acid of five cassava genotypes. Food Chem 92:615–520
Chen X, Xia Z, Fu Y, Lu C, Wang W (2010) Constructing a genetic linkage map using an F1 population of non-inbred parents in cassava (Manihot esculenta Crantz). Plant Mol Biol Rep 28:676–683
CIAT (2002) CIAT cassava distributions 2002. http://gisweb.ciat.cgiar.org/Mapserver/Africa_dhtml/africa_inicio_v3.html. Cited 30 Sept 2011
CIAT (2010) CIAT Amazon major crop distributions 2010. http://gismap.ciat.cgiar.org/egiron/IAMapserver/. Cited 30 Sept 2011
CIAT (2010a) A new future of cassava in Asia: Its use as food, feed and fuel to benefit the poor. Proc. 8th Regional Workshop, held in Vientiane, Lao PDR, Oct. 20–24, 2008
CLAYUCA (2011) http://www.clayuca.org/. Cited 30 Sept 2011
Compositae Genome Project (2011) http://compgenomics.ucdavis.edu/index.php. Cited 21 Dec 2011
COP (2011) www.cassavacop.org. Cited 30 Sept 2011
Dekkers JCM, Hospital F (2002) The use of molecular genetics in the improvement of agricultural populations. Nat Rev Genet 3:22–32
DeLacy IH, Fox PN, Mclaren G, Trethowan R, White JW (2009) A Conceptual model for describing processes of crop improvement in database structures. Crop Sci 49:2100–2112
ESTIMA (2011) University of Illinois. http://titan.biotec.uiuc.edu/cgi-bin/ESTWebsite/estima_start?seqSet=cassava. Cited 30 Sept 2011
FAO (2011) Food and agriculture: Cassava www.fao.org. Cited 10 Nov 2011
Ferguson ME, Hearne SJ, Close TJ, Wanamaker S, Moskal WA, Town CD, de Young J, Marri PR, Rabbi IY, de Villiers EP (2011a) Identification, validation and high-throughput genotyping of transcribed gene SNPs in cassava. Theor Appl Genet. doi:10.1007/s00122-011-1739-9
Ferguson ME, Rabbi IY, Kim DJ, Gedil M, Becerra Lopez-Lavalle LA, Okogbenin E (2011b) Molecular markers and their application to cassava breeding: past, present and future. Tropical Plant Biol. doi:10.1007/s12042-011-9087-0
Flicek PM, Amode R, Barrell D, Beal K, Brent S, Chen Y, Clapham P, Coates G, Fairley S, Fitzgerald S, Gordon L, Hendrix M, Hourlier T, Johnson N, Kähäri A, Keefe D, Keenan S, Kinsella R, Kokocinski F, Kulesha E et al (2011) Ensembl 2011. Nucleic Acids Res 39:D800–D806
Fregene M, Angel F, Gomez R, Rodriguez F, Chavarriaga P, Roca W, Tohme J, Bonierbale M (1997) A molecular genetic map of cassava (Manihot esculenta Crantz). TAG Theor Appl Genet 95:431–441
GenBank (2011) NCBI nucleotide search “Manihot esculenta”[porgn:__txid3983]’ http://www.ncbi.nlm.nih.gov/nuccore. Cited 10 Nov 2011
GenBank Growth (2011) NCBI http://www.ncbi.nlm.nih.gov/genbank/genbankstats.html. Cited 10 Nov 2011
GENESYS (2011) Gateway to Genetic Resources. http://www.genesys-pgr.org/. Cited 30 Sept 2011
GEOSHARE (2011) Purdue University. http://www.geoshareproject.org/. Cited 30 Sept 2011
GRAMENE (2011) Gramene: a resource for comparative grass genomics www.gramene.org. Cited 12 Dec 2011
Grant D, Nelson RT, Cannon SB, Shoemaker RC (2010) SoyBase, the USDA-ARS soybean genetics and genomics database. Nucl Acids Res 38(suppl 1):D843–D846
GRP (2011) CIAT Genetic Resources Program http://isa.ciat.cgiar.org/urg/main.do?language=en. Cited 30 Sept 2011
HarvEST (2011) Univeristy of California, Riverside. http://harvest.ucr.edu/. Cited 30 Sept 2011
Huang X, Wei X, Sang T, Zhao Q, Feng Q, Zhao Y, Li C, Zhu C, Lu T, Zhang Z, Li M, Fan D, Guo Y, Wang A, Wang L, Deng L, Li W, Lu Y, Weng Q, Liu K et al (2010) Genome-wide association studies of 14 agronomic traits in rice landraces. Nat Genet 42(11):961–969
IBP (2011) https://www.integratedbreeding.net/. Cited on 21 Dec 2011
ICASS (2011) https://www.integratedbreeding.net/crop-information/cassava. Cited on 21 Dec 2011
ICIS (2011) ICIS Wiki main page. http://www.icis.cgiar.org/icis/index.php/Main_Page. Cited on 26 Feb 2011
ICP (2005) IITA’s Integrated Cassava Project http://www.cassavabiz.org/. Cited 30 Sept 2011
IITA (2011) IITA’s Genebank http://genebank.iita.org/. Cited 30 Sept 2011
ITPGRFA (2011) EMBRAPA’s Genebank http://tirfaa.cenargen.embrapa.br/MCPDEnglish/pages/mcpdBancos/Listar.jsp?idioma=english. Cited 30 Sept 2011
Jatropha Predicted Gene (2011) Kazusa DNA Research Institute. http://www.kazusa.or.jp/jatropha/. Cited 30 Sept 2011
Jorge V, Fregene MA, Duque MC, Bonierbale MW, Tohme J, Verdier V (2000) Genetic mapping of resistance to bacterial blight disease in cassava (Manihot esculenta Crantz). TAG Theor Appl Genet 101:865–872
Kunkeaw S, Tangphatsornruang S, Smith DR, Triwitayakorn K (2010) Genetic linkage map of cassava (Manihot esculenta Crantz) based on AFLP and SSR markers. Plant Breed 129:112–115
Lokko Y, Anderson JV, Rudd S, Raji A, Horvath D, Mikel MA, Kim R, Liu L, Hernandez A, Dixon AG, Ingelbrecht IL (2007) Characterization of an 18,166 EST dataset for cassava (Manihot esculenta Crantz) enriched for drought-responsive genes. Plant Cell Rep 26(9):1605–1618
Lopez C, Jorge V, Piégu B, Mba C, Cortes D, Restrepo S, Soto M, Laudié M, Berger C, Cooke R, Delseny M, Tohme J, Verdier V (2004) A unigene catalogue of 5700 expressed genes in cassava. Plant Mol Biol 56(4):541–554
Lopez C, Quesada-Ocampo LM, Bohorquez A, Duque MC, Vargas J, Tohme J, Verdier V (2007) Mapping EST-derived SSRs and ESTs involved in resistance to bacterial blight in Manihot esculenta. Genome 50(12):1078–1088
Lu T, Lu G, Fan D, Zhu C, Li W, Zhao Q, Feng Q, Zhao Y, Guo Y, Li W, Huang X, Han B (2010) Function annotation of the rice transcriptome at single-nucleotide resolution by RNA-seq. Genome Res 20:1238–1249
Manyong VM, Dixon AGO, Makinde KO, Bokanga M, and Whyte J (2000) The contribution of IITA-imporved cassava to food security in sub-Saharan Africa: an impact study. International Institute of Tropical Agriculture. 13p
MapSpaM (2011) HarvestChoice. http://mapspam.info. Cited 30 Sept 2011
Maziya-Dixon B, Dixon AGO, Adebowale AA (2007) Targeting different end uses of cassava: genotypic variations for cyanogenic potentials and pasting properties. Int J Food Sci Tech 42:969–976
Mochida K, Shinozaki K (2010) Genomics and bioinformatics resources for crop improvement. Plant Cell Physiol 51(4):497–523
MOLCAS (2011) The cassava molecular diversity network. http://newapp.ciat.cgiar.org/molcas/. Cited 30 Sept 2011
Ndyetabula I, Legg J (2011) DEWN: a novel surveillance system IITA R4D Review, Issue 6. http://r4dreview.org/2011/04/dewn–a–novel–surveillance–system/
Okogbenin E, Fregene M (2003) Genetic mapping of QTLs affecting productivity and plant architecture in a full-sib cross from non-inbred parents in Cassava (Manihot esculenta Crantz.). Theor App Genet 107:1452–1462
Okogbenin E, Marin J, Fregene MA (2006) An SSR-based molecular genetic map of cassava. Euphytica 147:433–440
Okogbenin E, Marin J, Fregene M (2008) QTL analysis for early yield in a pseudo F2 population of cassava. Afr J Biotechnol 7:131–138
Oliver R, Lazo G, Lutz J, Rubenfield M, Tinker N, Anderson J, Wisniewski Morehead N, Adhikary D, Jellen E, Maughan PJ, Brown Guedira GL, Chao A, Beattie AD, Carson ML, Rines HW, Obert DE, Bonman JM, Jackson EW (2011) Model SNP development for complex genomes based on hexaploid oat using high-throughput 454 sequencing technology. BMC Genom 12(1):77
Patil BL, Ogwok E, Wagaba H, Mohammed IU, Yadav JS, Bagewadi B, Taylor NJ, Kreuze JF, Maruthi MN, Alicai T, Fauquet CM (2011) RNAi-mediated resistance to diverse isolates belonging to two virus species involved in Cassava brown streak disease. Mol Plant Pathol 12(1):31–41
Perez-Rodriguez P, Riano-Pachon DM, Guedes LG, Rensing SA, Kersten B, Mueller-Roeber B (2010) PlnTFDB: updated content and new features of the plant transcription factor database. Nucl Acids Res 38(suppl 1):D822–D827
Phytozome (2011) JGI Phytozome Cassava. http://www.phytozome.net/cassava. Cited 30 Sept 2011
Phytozome (2011a) JGI Phytozome Poplar. http://www.phytozome.net/poplar. Cited 30 Sept 2011
PIPRA (2011) PIPRA. http://www.pipra.org/. Cited 30 Sept 2011
PlantTFDB (2011) Peking University http://planttfdb.cbi.pku.edu.cn. Cited 30 Sept 2011
PlnTFDB (2011) University of Potsdam http://plntfdb.bio.uni-potsdam.de/v3.0/. Cited 30 Sept 2011
PMN (2011) Carnegie Institution for Science http://plantcyc.org/. Cited 30 Sept 2011
Prochnik S, Marri PR, Desany B, Rabinowicz PD, Kodira C, Mohiuddin M, Rodriguez F, Fauquet C, Tohme J, Harkins T, Rokhsar DS, Rounsley S (2011) The cassava genome: current progress, future directions. Tropical Plant Biol. doi:10.1007/s12042-011-9088-z
Ridley WP, Shillito RD, Coats I, Steiner HY, Shawgo M, Phillips A, Dussold P, Kurtyka L (2004) Development of the international life sciences institute crop composition database. J Food Compos Anal 17:423–438
Sakurai T, Plata G, Rodríguez-Zapata F, Seki M, Salcedo A, Toyoda A, Ishiwata A, Tohme J, Sakaki Y, Shinozaki K, Ishitani M (2007) Sequencing analysis of 20,000 full-length cDNA clones from cassava reveals lineage specific expansions in gene families related to stress response. BMC Plant Biol 7:66
Santana MA, Anderson JV, Horvath DP (2008) Comparative study of cassava responses to bacterial infection using Euphorbiaceae-specific microarrays. First Scientific Meeting of the Global Cassava Partnership (GCP-I). July 21–25, 2008, International Convention Center, Ghent, Belgium. Program # S4-2; Abstract book p. 68
Shrestha R, Arnaud E, Mauleon R, Senger M, Davenport GF, Hancock D, Morrison N, Bruskiewich R, McLaren G (2010) Multifunctional crop trait ontology for breeders’ data: field book, annotation, data discovery and semantic enrichment of the literature. AoB PLANTS v. 2010: plq008, doi:10.1093/aobpla/plq008.
SINGER (2011) CGIAR System-wide Information Network for Genetic Resources http://singer.cgiar.org/. Cited 30 Sept 2011
Swarbreck D, Wilks C, Lamesch P, Berardini TZ, Garcia-Hernandez M, Foerster H, Li D, Meyer T, Muller R, Ploetz L, Radenbaugh A, Singh S, Swing V, Tissier C, Zhang P, Huala E (2008) The Arabidopsis Information Resource (TAIR): gene structure and function annotation. Nucleic Acids Res 36:D1009–D1014
The Arabidopsis Genome Initiative (2000) Analysis of the genome sequence of the flowering plant Arabidopsis thaliana. Nature 408:796–815
The Gene Ontology Consortium (2000) Gene ontology: tool for the unification of biology. Nat Genet 25(1):25–29
The Uniprot Consortium (2011) Ongoing and future developments at the Universal Protein Resource. Nucleic Acids Res 39:D214–D219
transPLANT (2011) Trans-national Infrastructure for Plant Genomic Science http://cordis.europa.eu/fetch?CALLER=FP7_PROJ_EN&ACTION=D&DOC=7&CAT=PROJ&QUERY=013465f7dd2a:6aed:208bab6a&RCN=99709. cited 22 Dec 2011
Trebbi D, Maccaferri M, de Heer P, Sørensen A, Giuliani S, Salvi S, Sanguineti M, Massi A, van der Vossen E, Tuberosa R (2011) High-throughput SNP discovery and genotyping in durum wheat (Triticum durum Desf.). Theor Appl Genet 123(4):555–569
Tuskan GA et al (2006) The genome of black cottonwood, Populus trichocarpa (Torr. & Gray). Science 313(5793):1596–1604
Udensii UE, Tarawali G, Favour EU, Asumugha G, Ezedinma C, Okoye BC, Okarter C, Ilona P, Okechukwu R, Dixon A (2011) Adoption of selected improved cassava varieties among smallholder farmers in South-Eastern Nigeria. J Food Agr Environ 9(1):329–335
UniProtKB (2011) Search ‘organism:manihot AND organism:esculenta’ http://www.uniprot.org/. Cited 10 Nov 2011
Vanderschuren H, Alder A, Zhang P, Gruissem W (2009) Dose-dependent RNAi-mediated geminivirus resistance in the tropical root crop cassava. Plant Mol Biol 70:265–272
V-GET (2011) HarvestChoice. http://harvestchoice.org/production/biotic/mapping. Cited 30 Sept 2011
WHO (2011) WHO nutrition: http://www.who.int/nutrition/publications/micronutrients/en/. Cited 30 Sept 2011
Wydra K, Zinsou V, Jorge V, Verdier V (2004) Identification of Pathotypes of Xanthomonas axonopodis pv. manihotis in Africa and Detection of Quantitative Trait Loci and Markers for Resistance to Bacterial Blight of Cassava. Phytopathology 94:1084–1093
Xu X, Liu X, Ge S, Jensen JD, Hu F, Li X, Dong Y, Gutenkunst RN, Fang L, Huang L, Li J, He W, Zhang G, Zheng X, Zhang F, Li Y, Yu C, Kristiansen K, Zhang X, Wang J et al (2011) Resequencing 50 accessions of cultivated and wild rice yields markers for identifying agronomically important genes. Nat Biotechnol Adv Online Publ. doi:10.1038/nbt.2050
Yadav JS, Ogwok E, Wagaba H, Patil BL, Bagewadi B, Alicai T, Gaitan-Solis E, Taylor NJ, Fauquet CM (2011) RNAi-mediated resistance to Cassava brown streak Uganda virus in transgenic cassava. Mol Plant Pathol 12(7):677–687
Yang J, An D, Zhang P (2011) Expression profiling of cassava storage roots reveals an active process of glycolysis/gluconeogenesis. J Integr Plant Biol 53(3):193–211
You L, Wood S, Wood-Sichra U (2006) Generating global crop maps: from census to grid. IAAE (International Association of Agricultural Economists) Annual Conference, Gold Coast, Australia
Yu J, Hu S, Wang J et al (2002) A draft sequence of the rice genome (Oryza sativa L. ssp. indica). Science 296(5565):79–92
Zhang P, Dreher K, Karthikeyan A, Chi A, Pujar A, Caspi R, Karp P, Kirkup V, Latendresse M, Lee C, Mueller LA, Muller R, Rhee SY (2010) Creation of a genome-wide metabolic pathway database for populus trichocarpa using a new approach for reconstruction and curation of metabolic pathways for plants. Plant Physiol 153(4):1479–1491
Zhang H, Jin JP, Tang L, Zhao Y, Gu XC, Gao G, Luo JC (2011) PlantTFDB 2.0: update and improvement of the comprehensive plant transcription factor database. Nucleic Acids Res 39:D1114–D1117
Acknowledgements
The authors would like to thank the anonymous reviewers and acknowledge contributions from a number of members of the cassava community for reviewing the white paper draft upon which this review has been based:
Olalekan Akinbo, Luis Augusto Becerra Lopez Lavalle, Luiz Carvalho, Claude Fauquet, Melaku Gedil, Clair Hershey, Glenn Hyman, Andy Jarvis, Joseph Kamau, Pheneas Ntawuruhunga, Motoaki Seki, Peng Zhang
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Ayling, S., Ferguson, M., Rounsley, S. et al. Information Resources for Cassava Research and Breeding. Tropical Plant Biol. 5, 140–151 (2012). https://doi.org/10.1007/s12042-012-9093-x
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DOI: https://doi.org/10.1007/s12042-012-9093-x