{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T16:53:51Z","timestamp":1793379231252,"version":"4.5.0"},"reference-count":39,"publisher":"National Academy of Sciences","issue":"13","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2003,6,24]]},"abstract":"<jats:p>\n                    According to the present view, metastasis marks the end in a sequence of  genomic changes underlying the progression of an epithelial cell to a lethal  cancer. Here, we aimed to find out at what stage of tumor development  transformed cells leave the primary tumor and whether a defined genotype  corresponds to metastatic disease. To this end, we isolated single  disseminated cancer cells from bone marrow of breast cancer patients and  performed single-cell comparative genomic hybridization. We analyzed  disseminated tumor cells from patients after curative resection of the primary  tumor (stage M0), as presumptive progenitors of manifest metastasis, and from  patients with manifest metastasis (stage M1). Their genomic data were compared  with those from microdissected areas of matched primary tumors. Disseminated  cells from M0-stage patients displayed significantly fewer chromosomal  aberrations than primary tumors or cells from M1-stage patients (\n                    <jats:italic>P<\/jats:italic>\n                    &lt; 0.008 and\n                    <jats:italic>P<\/jats:italic>\n                    &lt; 0.0001, respectively), and their aberrations  appeared to be randomly generated. In contrast, primary tumors and M1 cells  harbored different and characteristic chromosomal imbalances. Moreover,  applying machine-learning methods for the classification of the genotypes, we  could correctly identify the presence or absence of metastatic disease in a  patient on the basis of a single-cell genome. We suggest that in breast  cancer, tumor cells may disseminate in a far less progressed genomic state  than previously thought, and that they acquire genomic aberrations typical of  metastatic cells thereafter. Thus, our data challenge the widely held view  that the precursors of metastasis are derived from the most advanced clone  within the primary tumor.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1331931100","type":"journal-article","created":{"date-parts":[[2003,6,24]],"date-time":"2003-06-24T13:47:39Z","timestamp":1056462459000},"page":"7737-7742","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":527,"title":["From latent disseminated cells to overt metastasis: Genetic analysis of  systemic breast cancer progression"],"prefix":"10.1073","volume":"100","author":[{"given":"Oleg","family":"Schmidt-Kittler","sequence":"first","affiliation":[{"name":"Institut f\u00fcr Immunologie,  Ludwig-Maximilians-Universit\u00e4t M\u00fcnchen, 80336 M\u00fcnchen, Germany;  phase-it Intelligent Solutions AG, 69115  Heidelberg, Germany; Zentralklinikum Augsburg,  II Medizinische Klinik, 86156 Augsburg, Germany;  Universit\u00e4ts Frauenklinik Frankfurt, 60590  Frankfurt, Germany; Institut f\u00fcr Pathologie,  Ludwig-Maximilians-Universit\u00e4t M\u00fcnchen, 80337 M\u00fcnchen, Germany;  Zentralklinikum Augsburg, Institut f\u00fcr  Pathologie, 86156 Augsburg, Germany;  Klinik Bad Trissl, 83080 Oberaudorf, ..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Ragg","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Immunologie,  Ludwig-Maximilians-Universit\u00e4t M\u00fcnchen, 80336 M\u00fcnchen, Germany;  phase-it Intelligent Solutions AG, 69115  Heidelberg, Germany; Zentralklinikum Augsburg,  II Medizinische Klinik, 86156 Augsburg, Germany;  Universit\u00e4ts Frauenklinik Frankfurt, 60590  Frankfurt, Germany; Institut f\u00fcr Pathologie,  Ludwig-Maximilians-Universit\u00e4t M\u00fcnchen, 80337 M\u00fcnchen, Germany;  Zentralklinikum Augsburg, Institut f\u00fcr  Pathologie, 86156 Augsburg, Germany;  Klinik Bad Trissl, 83080 Oberaudorf, ..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Daskalakis","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Immunologie,  Ludwig-Maximilians-Universit\u00e4t M\u00fcnchen, 80336 M\u00fcnchen, Germany;  phase-it Intelligent Solutions AG, 69115  Heidelberg, Germany; Zentralklinikum Augsburg,  II Medizinische Klinik, 86156 Augsburg, Germany;  Universit\u00e4ts Frauenklinik Frankfurt, 60590  Frankfurt, Germany; Institut f\u00fcr Pathologie,  Ludwig-Maximilians-Universit\u00e4t M\u00fcnchen, 80337 M\u00fcnchen, Germany;  Zentralklinikum Augsburg, Institut f\u00fcr  Pathologie, 86156 Augsburg, Germany;  Klinik Bad Trissl, 83080 Oberaudorf, ..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Granzow","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Immunologie,  Ludwig-Maximilians-Universit\u00e4t M\u00fcnchen, 80336 M\u00fcnchen, Germany;  phase-it Intelligent Solutions AG, 69115  Heidelberg, Germany; Zentralklinikum Augsburg,  II Medizinische Klinik, 86156 Augsburg, Germany;  Universit\u00e4ts Frauenklinik Frankfurt, 60590  Frankfurt, Germany; Institut f\u00fcr Pathologie,  Ludwig-Maximilians-Universit\u00e4t M\u00fcnchen, 80337 M\u00fcnchen, Germany;  Zentralklinikum Augsburg, Institut f\u00fcr  Pathologie, 86156 Augsburg, Germany;  Klinik Bad Trissl, 83080 Oberaudorf, ..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andre","family":"Ahr","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Immunologie,  Ludwig-Maximilians-Universit\u00e4t M\u00fcnchen, 80336 M\u00fcnchen, Germany;  phase-it Intelligent Solutions AG, 69115  Heidelberg, Germany; Zentralklinikum Augsburg,  II Medizinische Klinik, 86156 Augsburg, Germany;  Universit\u00e4ts Frauenklinik Frankfurt, 60590  Frankfurt, Germany; Institut f\u00fcr Pathologie,  Ludwig-Maximilians-Universit\u00e4t M\u00fcnchen, 80337 M\u00fcnchen, Germany;  Zentralklinikum Augsburg, Institut f\u00fcr  Pathologie, 86156 Augsburg, Germany;  Klinik Bad Trissl, 83080 Oberaudorf, ..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas J. F.","family":"Blankenstein","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Immunologie,  Ludwig-Maximilians-Universit\u00e4t M\u00fcnchen, 80336 M\u00fcnchen, Germany;  phase-it Intelligent Solutions AG, 69115  Heidelberg, Germany; Zentralklinikum Augsburg,  II Medizinische Klinik, 86156 Augsburg, Germany;  Universit\u00e4ts Frauenklinik Frankfurt, 60590  Frankfurt, Germany; Institut f\u00fcr Pathologie,  Ludwig-Maximilians-Universit\u00e4t M\u00fcnchen, 80337 M\u00fcnchen, Germany;  Zentralklinikum Augsburg, Institut f\u00fcr  Pathologie, 86156 Augsburg, Germany;  Klinik Bad Trissl, 83080 Oberaudorf, ..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manfred","family":"Kaufmann","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Immunologie,  Ludwig-Maximilians-Universit\u00e4t M\u00fcnchen, 80336 M\u00fcnchen, Germany;  phase-it Intelligent Solutions AG, 69115  Heidelberg, Germany; Zentralklinikum Augsburg,  II Medizinische Klinik, 86156 Augsburg, Germany;  Universit\u00e4ts Frauenklinik Frankfurt, 60590  Frankfurt, Germany; Institut f\u00fcr Pathologie,  Ludwig-Maximilians-Universit\u00e4t M\u00fcnchen, 80337 M\u00fcnchen, Germany;  Zentralklinikum Augsburg, Institut f\u00fcr  Pathologie, 86156 Augsburg, Germany;  Klinik Bad Trissl, 83080 Oberaudorf, ..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joachim","family":"Diebold","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Immunologie,  Ludwig-Maximilians-Universit\u00e4t M\u00fcnchen, 80336 M\u00fcnchen, Germany;  phase-it Intelligent Solutions AG, 69115  Heidelberg, Germany; Zentralklinikum Augsburg,  II Medizinische Klinik, 86156 Augsburg, Germany;  Universit\u00e4ts Frauenklinik Frankfurt, 60590  Frankfurt, Germany; Institut f\u00fcr Pathologie,  Ludwig-Maximilians-Universit\u00e4t M\u00fcnchen, 80337 M\u00fcnchen, Germany;  Zentralklinikum Augsburg, Institut f\u00fcr  Pathologie, 86156 Augsburg, Germany;  Klinik Bad Trissl, 83080 Oberaudorf, ..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans","family":"Arnholdt","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Immunologie,  Ludwig-Maximilians-Universit\u00e4t M\u00fcnchen, 80336 M\u00fcnchen, Germany;  phase-it Intelligent Solutions AG, 69115  Heidelberg, Germany; Zentralklinikum Augsburg,  II Medizinische Klinik, 86156 Augsburg, Germany;  Universit\u00e4ts Frauenklinik Frankfurt, 60590  Frankfurt, Germany; Institut f\u00fcr Pathologie,  Ludwig-Maximilians-Universit\u00e4t M\u00fcnchen, 80337 M\u00fcnchen, Germany;  Zentralklinikum Augsburg, Institut f\u00fcr  Pathologie, 86156 Augsburg, Germany;  Klinik Bad Trissl, 83080 Oberaudorf, ..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Immunologie,  Ludwig-Maximilians-Universit\u00e4t M\u00fcnchen, 80336 M\u00fcnchen, Germany;  phase-it Intelligent Solutions AG, 69115  Heidelberg, Germany; Zentralklinikum Augsburg,  II Medizinische Klinik, 86156 Augsburg, Germany;  Universit\u00e4ts Frauenklinik Frankfurt, 60590  Frankfurt, Germany; Institut f\u00fcr Pathologie,  Ludwig-Maximilians-Universit\u00e4t M\u00fcnchen, 80337 M\u00fcnchen, Germany;  Zentralklinikum Augsburg, Institut f\u00fcr  Pathologie, 86156 Augsburg, Germany;  Klinik Bad Trissl, 83080 Oberaudorf, ..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joachim","family":"Bischoff","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Immunologie,  Ludwig-Maximilians-Universit\u00e4t M\u00fcnchen, 80336 M\u00fcnchen, Germany;  phase-it Intelligent Solutions AG, 69115  Heidelberg, Germany; Zentralklinikum Augsburg,  II Medizinische Klinik, 86156 Augsburg, Germany;  Universit\u00e4ts Frauenklinik Frankfurt, 60590  Frankfurt, Germany; Institut f\u00fcr Pathologie,  Ludwig-Maximilians-Universit\u00e4t M\u00fcnchen, 80337 M\u00fcnchen, Germany;  Zentralklinikum Augsburg, Institut f\u00fcr  Pathologie, 86156 Augsburg, Germany;  Klinik Bad Trissl, 83080 Oberaudorf, ..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Detlev","family":"Harich","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Immunologie,  Ludwig-Maximilians-Universit\u00e4t M\u00fcnchen, 80336 M\u00fcnchen, Germany;  phase-it Intelligent Solutions AG, 69115  Heidelberg, Germany; Zentralklinikum Augsburg,  II Medizinische Klinik, 86156 Augsburg, Germany;  Universit\u00e4ts Frauenklinik Frankfurt, 60590  Frankfurt, Germany; Institut f\u00fcr Pathologie,  Ludwig-Maximilians-Universit\u00e4t M\u00fcnchen, 80337 M\u00fcnchen, Germany;  Zentralklinikum Augsburg, Institut f\u00fcr  Pathologie, 86156 Augsburg, Germany;  Klinik Bad Trissl, 83080 Oberaudorf, ..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G\u00fcnter","family":"Schlimok","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Immunologie,  Ludwig-Maximilians-Universit\u00e4t M\u00fcnchen, 80336 M\u00fcnchen, Germany;  phase-it Intelligent Solutions AG, 69115  Heidelberg, Germany; Zentralklinikum Augsburg,  II Medizinische Klinik, 86156 Augsburg, Germany;  Universit\u00e4ts Frauenklinik Frankfurt, 60590  Frankfurt, Germany; Institut f\u00fcr Pathologie,  Ludwig-Maximilians-Universit\u00e4t M\u00fcnchen, 80337 M\u00fcnchen, Germany;  Zentralklinikum Augsburg, Institut f\u00fcr  Pathologie, 86156 Augsburg, Germany;  Klinik Bad Trissl, 83080 Oberaudorf, ..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gert","family":"Riethm\u00fcller","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Immunologie,  Ludwig-Maximilians-Universit\u00e4t M\u00fcnchen, 80336 M\u00fcnchen, Germany;  phase-it Intelligent Solutions AG, 69115  Heidelberg, Germany; Zentralklinikum Augsburg,  II Medizinische Klinik, 86156 Augsburg, Germany;  Universit\u00e4ts Frauenklinik Frankfurt, 60590  Frankfurt, Germany; Institut f\u00fcr Pathologie,  Ludwig-Maximilians-Universit\u00e4t M\u00fcnchen, 80337 M\u00fcnchen, Germany;  Zentralklinikum Augsburg, Institut f\u00fcr  Pathologie, 86156 Augsburg, Germany;  Klinik Bad Trissl, 83080 Oberaudorf, ..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roland","family":"Eils","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Immunologie,  Ludwig-Maximilians-Universit\u00e4t M\u00fcnchen, 80336 M\u00fcnchen, Germany;  phase-it Intelligent Solutions AG, 69115  Heidelberg, Germany; Zentralklinikum Augsburg,  II Medizinische Klinik, 86156 Augsburg, Germany;  Universit\u00e4ts Frauenklinik Frankfurt, 60590  Frankfurt, Germany; Institut f\u00fcr Pathologie,  Ludwig-Maximilians-Universit\u00e4t M\u00fcnchen, 80337 M\u00fcnchen, Germany;  Zentralklinikum Augsburg, Institut f\u00fcr  Pathologie, 86156 Augsburg, Germany;  Klinik Bad Trissl, 83080 Oberaudorf, ..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph A.","family":"Klein","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Immunologie,  Ludwig-Maximilians-Universit\u00e4t M\u00fcnchen, 80336 M\u00fcnchen, Germany;  phase-it Intelligent Solutions AG, 69115  Heidelberg, Germany; Zentralklinikum Augsburg,  II Medizinische Klinik, 86156 Augsburg, Germany;  Universit\u00e4ts Frauenklinik Frankfurt, 60590  Frankfurt, Germany; Institut f\u00fcr Pathologie,  Ludwig-Maximilians-Universit\u00e4t M\u00fcnchen, 80337 M\u00fcnchen, Germany;  Zentralklinikum Augsburg, Institut f\u00fcr  Pathologie, 86156 Augsburg, Germany;  Klinik Bad Trissl, 83080 Oberaudorf, ..."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2003,6,13]]},"reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(90)90186-I"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/415530a"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/418823a"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81683-9"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1994.12.6.1272"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1006\/scbi.2001.0386"},{"key":"e_1_3_2_7_2","first-page":"560","volume":"419","year":"2002","unstructured":"Bernards, R. & Weinberg, R. A. (2002) Nature 419, 560 (lett.).","journal-title":"Nature"},{"key":"e_1_3_2_8_2","first-page":"559","volume":"419","year":"2002","unstructured":"Edwards, P. A. (2002) Nature 419, 559-560 (lett.).","journal-title":"Nature"},{"key":"e_1_3_2_9_2","first-page":"560","volume":"419","year":"2002","unstructured":"Sherley, J. L. (2002) Nature 419, 560 (lett.).","journal-title":"Nature"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200002243420801"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/91.13.1113"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2001.19.16.3669"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00431541"},{"key":"e_1_3_2_14_2","first-page":"4712","volume":"51","year":"1991","unstructured":"Pantel, K., Schlimok, G., Kutter, D., Schaller, G., Genz, T., Wiebecke, B., Backmann, R., Funke, I. & Riethm\u00fcller, G. (1991) Cancer Res. 51, 4712-4715.1873815","journal-title":"Cancer Res."},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/0165-4608(95)00189-1"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.8.4494"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(02)09838-0"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)64155-7"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng911"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0925-2312(01)00624-5"},{"key":"e_1_3_2_21_2","first-page":"61","volume":"15","year":"2002","unstructured":"Ragg, T. (2002) in AI Commun. 15, 61-74.","journal-title":"AI Commun."},{"key":"e_1_3_2_22_2","doi-asserted-by":"crossref","unstructured":"Bishop C. M. (1995) Neural Networks for  Pattern Recognition (Oxford Univ. Press Oxford).","DOI":"10.1201\/9781420050646.ptb6"},{"key":"e_1_3_2_23_2","first-page":"93","volume":"33","year":"2001","unstructured":"Empson, M. B. (2001) Pathology 33, 93-95.11280616","journal-title":"Pathology"},{"key":"e_1_3_2_24_2","unstructured":"Press W. H. Flannery B. P. Teukolsky S. A. & Vetterling W. T. (1993) Numerical Recipes in C (Cambridge Univ. Press Cambridge U.K.)."},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.6.2156"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.25.14863"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/35020592"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.297.5581.565"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1006\/scbi.1999.0131"},{"key":"e_1_3_2_30_2","first-page":"4855","volume":"54","year":"1994","unstructured":"Greenblatt, M. S., Bennett, W. P., Hollstein, M. & Harris, C. C. (1994) Cancer Res. 54, 4855-4878.8069852","journal-title":"Cancer Res."},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt0402-387"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1204505"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0215(20000101)85:1<82::AID-IJC15>3.0.CO;2-S"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9896(199903)187:4<396::AID-PATH286>3.0.CO;2-L"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-2264(199708)19:4<267::AID-GCC9>3.0.CO;2-V"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-2264(199806)22:2<122::AID-GCC6>3.0.CO;2-Z"},{"key":"e_1_3_2_37_2","first-page":"1597","volume":"57","year":"1997","unstructured":"Kuukasjarvi, T., Karhu, R., Tanner, M., Kahkonen, M., Schaffer, A., Nupponen, N., Pennanen, S., Kallioniemi, A., Kallioniemi, O. P. & Isola, J. (1997) Cancer Res. 57, 1597-1604.9108466","journal-title":"Cancer Res."},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-4608(01)00645-8"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0334858100"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.1331931100","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,25]],"date-time":"2022-04-25T21:23:51Z","timestamp":1650921831000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.1331931100"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,6,13]]},"references-count":39,"journal-issue":{"issue":"13","published-print":{"date-parts":[[2003,6,24]]}},"alternative-id":["10.1073\/pnas.1331931100"],"URL":"https:\/\/doi.org\/10.1073\/pnas.1331931100","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.1011145.195256","asserted-by":"object"}]},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2003,6,13]]},"assertion":[{"value":"2003-04-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2003-05-08","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2003-06-13","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}