278 lines
34 KiB
XML
278 lines
34 KiB
XML
<document id="B5BD13224BBFD9F360DF65E9A8C520D0" ID-DOI="10.1126/science.1155006" ID-GBIF-Dataset="fda4077a-e5f1-4464-ac91-b7706396303b" ID-Zenodo-Dep="3746046" IM.metadata_requiresApprovalFor="plazi" IM.taxonomicNames_requiresApprovalFor="plazi" checkinTime="1586423499357" checkinUser="jeremy" docAuthor="Pavel A. Pevzner, Sangtae Kim & Julio Ng" docDate="2008" docId="A0283F40D65CFFD7A359FDD4FA80F8F0" docLanguage="en" docName="Pevzneretal2008.pdf" docOrigin="Science 321" docStyle="DocumentStyle{}" docTitle="Tyrannosaurus rex" docType="treatment" docVersion="9" lastPageNumber="1040" masterDocId="5C114738D65CFFD7A339FFB5FFA6FFFA" masterDocTitle="Comment on “ Protein sequences from mastodon and Tyrannosaurus rex revealed by mass spectrometry ”" masterLastPageNumber="1040" masterPageNumber="1040" pageNumber="1040" updateTime="1698736721676" updateUser="plazi">
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<mods:mods id="480EC4939DFBB63FCC5A6458169C0132" xmlns:mods="http://www.loc.gov/mods/v3">
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<mods:titleInfo id="7BAC96AD726A981AD5E0CE16F21E7224">
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<mods:title id="861B496A9A0EE7F3E37C726654CC1E46">Comment on “ Protein sequences from mastodon and Tyrannosaurus rex revealed by mass spectrometry ”</mods:title>
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<mods:name id="3B4680725E13D599D91DED3D593755F7" type="personal">
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<mods:roleTerm id="2C5D8E9C1801606D9C6B0EF724FAC7AD">Author</mods:roleTerm>
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<mods:namePart id="26A9AE9307658B352D7B6EFEE0340A97">Pavel A. Pevzner</mods:namePart>
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<mods:affiliation id="DF6CF4AF25D44659A073767E65D6CBBB">Department of Computer Science and Engineering, University of California, San Diego, 9500 Gilman Drive, Mail Code 0404, La Jolla, CA 92093 – 0404, USA.</mods:affiliation>
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<mods:nameIdentifier id="85224A2DE9F09EE10A74A66EF85B7DA5" type="email">ppevzner@cs.ucsd.edu</mods:nameIdentifier>
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<mods:namePart id="42DDE6BDBAF6A4E3BEAB94D93DE3642E">Sangtae Kim</mods:namePart>
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<mods:affiliation id="88DEBC2383378712BC5AD63128F4CE06">Department of Computer Science and Engineering, University of California, San Diego, 9500 Gilman Drive, Mail Code 0404, La Jolla, CA 92093 – 0404, USA.</mods:affiliation>
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<mods:roleTerm id="08CB14091CD0C3A12EF967330CC8DB0F">Author</mods:roleTerm>
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<mods:namePart id="264385061795C600683C8E4A6D1D4852">Julio Ng</mods:namePart>
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<mods:affiliation id="E1FB910BCFE58F17A0CADA4EB082DC82">Department of Computer Science and Engineering, University of California, San Diego, 9500 Gilman Drive, Mail Code 0404, La Jolla, CA 92093 – 0404, USA.</mods:affiliation>
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<mods:title id="EDE078813F0C19EAA459ED35B8E89DA2">Science</mods:title>
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<mods:part id="8049F0790CCCD02A523531F2759CBF0F">
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<mods:date id="2F57AC438C91FE8948766B35BF1ABE93">2008</mods:date>
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<mods:number id="AB22EBD8A6AFAB838BEC5DA3208D129A">2008-08-24</mods:number>
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<mods:number id="1725FF4B164E098B777231188D028403">321</mods:number>
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<mods:identifier id="9F7959E413610B861144B46B9847BFD8" type="DOI">10.1126/science.1155006</mods:identifier>
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<treatment id="A0283F40D65CFFD7A359FDD4FA80F8F0" ID-DOI="http://doi.org/10.5281/zenodo.3809413" ID-GBIF-Taxon="163540450" ID-Zenodo-Dep="3809413" LSID="urn:lsid:plazi:treatment:A0283F40D65CFFD7A359FDD4FA80F8F0" httpUri="http://treatment.plazi.org/id/A0283F40D65CFFD7A359FDD4FA80F8F0" lastPageNumber="1040" pageId="0" pageNumber="1040">
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<subSubSection id="609BDDDDD65CFFD7A359FDD4FEB0F985" pageId="0" pageNumber="1040" type="discussion">
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<paragraph id="283E8E56D65CFFD7A359FDD4FDBAFCAC" blockId="0.[96,540,609,1746]" pageId="0" pageNumber="1040">Imagine a monkey typing random keys on a typewriter and let us assume that the monkey is given 100,000 attempts to generate six-letter words. One would be surprised if the monkey typed a six-letter word from Webster’ s dictionary on the first attempt; indeed, the probability of this is rather low. However, nobody would be surprised if some of the 100,000 words turned out to be correctly spelled English words.</paragraph>
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<paragraph id="283E8E56D65CFFD7A3B9FCE8FE17FB72" blockId="0.[96,540,609,1746]" pageId="0" pageNumber="1040">Now imagine a boy who watches the monkey and discovers that 7 out of 100,000 words are actually spelled correctly. The boy is so surprised that he writes a paper called “My monkey can spell!” and publishes it in a scientific journal. Some scientists are not convinced, and they request the list of all words the monkey generated in addition to the seven correctly spelled words. The boy does not understand the reason for such requests; indeed, if all other words are just junk, what is the point of asking for them?</paragraph>
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<paragraph id="283E8E56D65CFFD7A3B9FB3AFEB0F985" blockId="0.[96,540,609,1746]" pageId="0" pageNumber="1040">One often feels like a monkey (and a boy) when trying to interpret peptide mass spectra. Indeed, a randomly chosen spectrum can easily match a word in Webster (if English letters are interpreted as amino acids) or in any protein database. Scientists fail to interpret the lion’ s share of mass spectra generated worldwide, resulting in billions of uninterpreted or “junk” spectra. If we matched these junk spectra against Webster we would surely find that some of them spell English words. Unfortunately, we would not be able to publish a paper called “Mass spectrometers can spell!” because false protein identifications are unavoidable in the field of proteomics. Scientists learned how to cope with them by establishing the Proteomics Publication Guidelines that require authors to provide the error rates of their identifications.</paragraph>
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</subSubSection>
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<subSubSection id="609BDDDDD65CFFD7A3B9F933FD43FD8C" pageId="0" pageNumber="1040" type="nomenclature">
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<paragraph id="283E8E56D65CFFD7A3B9F933FD43FD8C" blockId="0.[96,540,609,1746]" lastBlockId="0.[571,1014,609,1914]" pageId="0" pageNumber="1040">
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Asara
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<emphasis id="1AF55244D65CFFD7A387F933FF4FF961" box="[190,233,1670,1691]" italics="true" pageId="0" pageNumber="1040">et al</emphasis>
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. (
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<bibRefCitation id="4C10F3A7D65CFFD7A3C6F933FEADF961" author="J. M. Asara & M. H. Schweitzer & L. M. Freimark & M. Phillips & L. C. cantley" box="[255,267,1670,1691]" journalOrPublisher="Science" pageId="0" pageNumber="1040" pagination="280" part="316" refId="ref1497" refString="1. J. M. Asara, M. H. Schweitzer, L. M. Freimark, M. Phillips, L. C. Cantley, Science 316, 280 (2007)." type="journal article" year="2007">
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<emphasis id="1AF55244D65CFFD7A3C6F933FEADF961" box="[255,267,1670,1691]" italics="true" pageId="0" pageNumber="1040">1</emphasis>
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</bibRefCitation>
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) reported the sequencing of proteins from 68-million-year-old
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<taxonomicName id="EF81F5D5D65CFFD7A29BF914FE70F94C" authority="Osborn, 1905" box="[418,470,1697,1718]" class="Reptilia" family="Tyrannosauridae" genus="Tyrannosaurus" kingdom="Animalia" order="Dinosauria" pageId="0" pageNumber="1040" phylum="Chordata" rank="species" species="rex">
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<emphasis id="1AF55244D65CFFD7A29BF914FE70F94C" box="[418,470,1697,1718]" italics="true" pageId="0" pageNumber="1040">T. rex</emphasis>
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</taxonomicName>
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fossils and established similarities between dinosaur and chicken genomes.
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</paragraph>
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</subSubSection>
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<subSubSection id="609BDDDDD65CFFD7A1D0FDD4FD7EFC77" pageId="0" pageNumber="1040" type="discussion">
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<paragraph id="283E8E56D65CFFD7A1D0FDD4FD7EFC77" blockId="0.[571,1014,609,1914]" pageId="0" pageNumber="1040">
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The authors generated seven
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<taxonomicName id="EF81F5D5D65CFFD7A102FDC8FDCDFD68" authority="Osborn, 1905" box="[571,619,637,658]" class="Reptilia" family="Tyrannosauridae" genus="Tyrannosaurus" kingdom="Animalia" order="Dinosauria" pageId="0" pageNumber="1040" phylum="Chordata" rank="species" species="rex">
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<emphasis id="1AF55244D65CFFD7A102FDC8FDCDFD68" box="[571,619,637,658]" italics="true" pageId="0" pageNumber="1040">T. rex</emphasis>
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</taxonomicName>
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peptides by matching mass spectra against collagen proteins. They did not reveal all generated spectra and never specified exactly how many spectra were generated. Because there are false identifications in every mass spectrometry experiment, without addressing the statistical significance problem, the results of (
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<bibRefCitation id="4C10F3A7D65CFFD7A0A2FC90FC00FCC0" author="J. M. Asara & M. H. Schweitzer & L. M. Freimark & M. Phillips & L. C. cantley" box="[923,934,805,826]" journalOrPublisher="Science" pageId="0" pageNumber="1040" pagination="280" part="316" refId="ref1497" refString="1. J. M. Asara, M. H. Schweitzer, L. M. Freimark, M. Phillips, L. C. Cantley, Science 316, 280 (2007)." type="journal article" year="2007">
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<emphasis id="1AF55244D65CFFD7A0A2FC90FC00FCC0" box="[923,934,805,826]" italics="true" pageId="0" pageNumber="1040">1</emphasis>
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</bibRefCitation>
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) are no more convincing than the first sensational report of dinosaur DNA published in
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<emphasis id="1AF55244D65CFFD7A069FCE8FC33FC88" box="[848,917,861,882]" italics="true" pageId="0" pageNumber="1040">Science</emphasis>
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more than a decade ago (
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<bibRefCitation id="4C10F3A7D65CFFD7A186FCCDFD6CFC77" author="S. Woodward & N. Weyand & M. Bunnell" box="[703,714,888,909]" journalOrPublisher="Science" pageId="0" pageNumber="1040" pagination="1229" part="266" refId="ref1542" refString="2. S. Woodward, N. Weyand, M. Bunnell, Science 266, 1229 (1994)." type="journal article" year="1994">
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<emphasis id="1AF55244D65CFFD7A186FCCDFD6CFC77" box="[703,714,888,909]" italics="true" pageId="0" pageNumber="1040">2</emphasis>
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</bibRefCitation>
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).
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</paragraph>
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</subSubSection>
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<subSubSection id="609BDDDDD65CFFD7A162FC21FA80F8F0" pageId="0" pageNumber="1040" type="discussion">
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<paragraph id="283E8E56D65CFFD7A162FC21FD46F8B8" blockId="0.[571,1014,609,1914]" pageId="0" pageNumber="1040">
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In the spring of 2007, we notified Asara and
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<emphasis id="1AF55244D65CFFD7A102FC05FD26FC3F" box="[571,640,944,965]" italics="true" pageId="0" pageNumber="1040">Science</emphasis>
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of concerns about the statistical significance of some of the peptides. In a subsequent clarification letter (
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<bibRefCitation id="4C10F3A7D65CFFD7A1DDFC5DFD49FC07" author="J. M. Asara" box="[740,751,1000,1021]" journalOrPublisher="Science" pageId="0" pageNumber="1040" pagination="1324" part="317" refId="ref1564" refString="3. J. M. Asara et al., Science 317, 1324 (2007)." type="journal article" year="2007">
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<emphasis id="1AF55244D65CFFD7A1DDFC5DFD49FC07" box="[740,751,1000,1021]" italics="true" pageId="0" pageNumber="1040">3</emphasis>
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</bibRefCitation>
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), Asara
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<emphasis id="1AF55244D65CFFD7A002FC5DFCC4FC07" box="[827,866,1000,1021]" italics="true" pageId="0" pageNumber="1040">et al</emphasis>
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. acknowledged some of the problems with their analysis in (
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<bibRefCitation id="4C10F3A7D65CFFD7A0E4FBB1FC4EFBE3" author="J. M. Asara & M. H. Schweitzer & L. M. Freimark & M. Phillips & L. C. cantley" box="[989,1000,1028,1049]" journalOrPublisher="Science" pageId="0" pageNumber="1040" pagination="280" part="316" refId="ref1497" refString="1. J. M. Asara, M. H. Schweitzer, L. M. Freimark, M. Phillips, L. C. Cantley, Science 316, 280 (2007)." type="journal article" year="2007">
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<emphasis id="1AF55244D65CFFD7A0E4FBB1FC4EFBE3" box="[989,1000,1028,1049]" italics="true" pageId="0" pageNumber="1040">1</emphasis>
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</bibRefCitation>
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). In particular, they stated, “We have determined that one of the reported
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<taxonomicName id="EF81F5D5D65CFFD7A013FB89FCF9FBAB" authority="Osborn, 1905" box="[810,863,1084,1105]" class="Reptilia" family="Tyrannosauridae" genus="Tyrannosaurus" kingdom="Animalia" order="Dinosauria" pageId="0" pageNumber="1040" phylum="Chordata" rank="species" species="rex">
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<emphasis id="1AF55244D65CFFD7A013FB89FCF9FBAB" box="[810,863,1084,1105]" italics="true" pageId="0" pageNumber="1040">T. rex</emphasis>
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</taxonomicName>
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spectra for the peptide GLVGAPGLRGLPGK is statistically insignificant when searched against large protein databases....” (
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<bibRefCitation id="4C10F3A7D65CFFD7A1FCFB3AFD76FB5E" author="J. M. Asara" box="[709,720,1167,1188]" journalOrPublisher="Science" pageId="0" pageNumber="1040" pagination="1324" part="317" refId="ref1564" refString="3. J. M. Asara et al., Science 317, 1324 (2007)." type="journal article" year="2007">
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<emphasis id="1AF55244D65CFFD7A1FCFB3AFD76FB5E" box="[709,720,1167,1188]" italics="true" pageId="0" pageNumber="1040">3</emphasis>
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</bibRefCitation>
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,
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<emphasis id="1AF55244D65CFFD7A1DAFB3AFD48FB5E" box="[739,750,1167,1188]" italics="true" pageId="0" pageNumber="1040">4</emphasis>
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). By admitting this point, Asara
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<emphasis id="1AF55244D65CFFD7A1BBFB1EFD13FB3A" box="[642,693,1195,1216]" italics="true" pageId="0" pageNumber="1040">et al</emphasis>
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. implicitly (and probably unknowingly) acknowledged a much bigger problem with their original study (
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<bibRefCitation id="4C10F3A7D65CFFD7A05EFB56FCD4FB02" author="J. M. Asara & M. H. Schweitzer & L. M. Freimark & M. Phillips & L. C. cantley" box="[871,882,1251,1272]" journalOrPublisher="Science" pageId="0" pageNumber="1040" pagination="280" part="316" refId="ref1497" refString="1. J. M. Asara, M. H. Schweitzer, L. M. Freimark, M. Phillips, L. C. Cantley, Science 316, 280 (2007)." type="journal article" year="2007">
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<emphasis id="1AF55244D65CFFD7A05EFB56FCD4FB02" box="[871,882,1251,1272]" italics="true" pageId="0" pageNumber="1040">1</emphasis>
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</bibRefCitation>
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). Indeed, the statistical significance (e.g., false positive rate or FPR) is a number that needs to be computed, but Asara
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<emphasis id="1AF55244D65CFFD7A14EFA82FD06FAB6" box="[631,672,1335,1356]" italics="true" pageId="0" pageNumber="1040">et al</emphasis>
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. (
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<bibRefCitation id="4C10F3A7D65CFFD7A18CFA82FD66FAB6" author="J. M. Asara" box="[693,704,1335,1356]" journalOrPublisher="Science" pageId="0" pageNumber="1040" pagination="1324" part="317" refId="ref1564" refString="3. J. M. Asara et al., Science 317, 1324 (2007)." type="journal article" year="2007">
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<emphasis id="1AF55244D65CFFD7A18CFA82FD66FAB6" box="[693,704,1335,1356]" italics="true" pageId="0" pageNumber="1040">3</emphasis>
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</bibRefCitation>
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) never described how they computed statistical significance, and it is not clear whether they tried. If they computed the statistical significance, they would discern that other
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<taxonomicName id="EF81F5D5D65CFFD7A102FA13FDD4FA41" authority="Osborn, 1905" box="[571,626,1446,1467]" class="Reptilia" family="Tyrannosauridae" genus="Tyrannosaurus" kingdom="Animalia" order="Dinosauria" pageId="0" pageNumber="1040" phylum="Chordata" rank="species" species="rex">
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<emphasis id="1AF55244D65CFFD7A102FA13FDD4FA41" box="[571,626,1446,1467]" italics="true" pageId="0" pageNumber="1040">T. rex</emphasis>
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</taxonomicName>
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peptides do not fare much better. For example, it turns out that there are thousands of peptides that match the fifth
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<taxonomicName id="EF81F5D5D65CFFD7A07FFA6BFCDEFA09" authority="Osborn, 1905" box="[838,888,1502,1523]" class="Reptilia" family="Tyrannosauridae" genus="Tyrannosaurus" kingdom="Animalia" order="Dinosauria" pageId="0" pageNumber="1040" phylum="Chordata" rank="species" species="rex">
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<emphasis id="1AF55244D65CFFD7A07FFA6BFCDEFA09" box="[838,888,1502,1523]" italics="true" pageId="0" pageNumber="1040">T. rex</emphasis>
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</taxonomicName>
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spectrum reported in (
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<bibRefCitation id="4C10F3A7D65CFFD7A1A1FA4FFD05F9F5" author="J. M. Asara & M. H. Schweitzer & L. M. Freimark & M. Phillips & L. C. cantley" box="[664,675,1530,1551]" journalOrPublisher="Science" pageId="0" pageNumber="1040" pagination="280" part="316" refId="ref1497" refString="1. J. M. Asara, M. H. Schweitzer, L. M. Freimark, M. Phillips, L. C. Cantley, Science 316, 280 (2007)." type="journal article" year="2007">
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<emphasis id="1AF55244D65CFFD7A1A1FA4FFD05F9F5" box="[664,675,1530,1551]" italics="true" pageId="0" pageNumber="1040">1</emphasis>
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</bibRefCitation>
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,
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<bibRefCitation id="4C10F3A7D65CFFD7A196FA4FFD1CF9F5" author="J. M. Asara" box="[687,698,1530,1551]" journalOrPublisher="Science" pageId="0" pageNumber="1040" pagination="1324" part="317" refId="ref1564" refString="3. J. M. Asara et al., Science 317, 1324 (2007)." type="journal article" year="2007">
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<emphasis id="1AF55244D65CFFD7A196FA4FFD1CF9F5" box="[687,698,1530,1551]" italics="true" pageId="0" pageNumber="1040">3</emphasis>
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</bibRefCitation>
|
||
) even better than the alleged
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<taxonomicName id="EF81F5D5D65CFFD7A0FAFA4FFC55F9F5" authority="Osborn, 1905" box="[963,1011,1530,1551]" class="Reptilia" family="Tyrannosauridae" genus="Tyrannosaurus" kingdom="Animalia" order="Dinosauria" pageId="0" pageNumber="1040" phylum="Chordata" rank="species" species="rex">
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<emphasis id="1AF55244D65CFFD7A0FAFA4FFC55F9F5" box="[963,1011,1530,1551]" italics="true" pageId="0" pageNumber="1040">T. rex</emphasis>
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</taxonomicName>
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peptide GVVGLP*GQR [FPR or spectral probability equal to 1.3 × 10
|
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<superScript id="DFF4231ED65CFFD7A02EF999FC8FF9C0" attach="left" box="[791,809,1580,1594]" fontSize="6" pageId="0" pageNumber="1040">−6</superScript>
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(
|
||
<bibRefCitation id="4C10F3A7D65CFFD7A00FF987FCE7F9BD" author="S. Kim & N. Gupta & P. A. Pevzner" box="[822,833,1586,1607]" journalOrPublisher="J. Proteome Res." pageId="0" pageNumber="1040" pagination="3354" part="7" refId="ref1677" refString="5. S. Kim, N. Gupta, P. A. Pevzner, J. Proteome Res. 7, 3354 (2008)." type="journal article" year="2008">
|
||
<emphasis id="1AF55244D65CFFD7A00FF987FCE7F9BD" box="[822,833,1586,1607]" italics="true" pageId="0" pageNumber="1040">5</emphasis>
|
||
</bibRefCitation>
|
||
)]. This implies that if one tries to match this spectrum against a small database of 10
|
||
<superScript id="DFF4231ED65CFFD7A1F3F9D1FD75F988" attach="left" box="[714,723,1636,1650]" fontSize="6" pageId="0" pageNumber="1040">6</superScript>
|
||
amino acids, there is a good chance of matching this spectrum simply by chance. Or, equivalently, if one tries to match 1000 arbitrary spectra of similar quality against an arbitrary database of 1000 amino acids, there is a good chance to find an interpretation that is even better than the alleged
|
||
<taxonomicName id="EF81F5D5D65CFFD7A057F8A4FC03F8DC" authority="Osborn, 1905" box="[878,933,1809,1830]" class="Reptilia" family="Tyrannosauridae" genus="Tyrannosaurus" kingdom="Animalia" order="Dinosauria" pageId="0" pageNumber="1040" phylum="Chordata" rank="species" species="rex">
|
||
<emphasis id="1AF55244D65CFFD7A057F8A4FC03F8DC" box="[878,933,1809,1830]" italics="true" pageId="0" pageNumber="1040">T. rex</emphasis>
|
||
</taxonomicName>
|
||
peptide GVVGLP*GQR.
|
||
</paragraph>
|
||
<subSubSection id="609BDDDDD65CFFD7A359F8B0FE15F8BE" pageId="0" pageNumber="1040" type="description">
|
||
<footnote id="4B9A9258D65CFFD7A359F8B0FE15F8BE" pageId="0" pageNumber="1040">
|
||
<paragraph id="283E8E56D65CFFD7A359F8B0FE15F8BE" blockId="0.[96,539,1797,1860]" pageId="0" pageNumber="1040">
|
||
<docAuthorAffiliation id="309E4135D65CFFD7A359F8B0FE15F8BE" pageId="0" pageNumber="1040">
|
||
Department of Computer
|
||
<docJournal id="AD1CB5E7D65CFFD7A212F8B0FEC5F8ED" box="[299,355,1797,1815]" pageId="0" pageNumber="1040">Science</docJournal>
|
||
and Engineering, University of California, San Diego, 9500 Gilman Drive, Mail Code 0404, La Jolla, CA 92093–0404, USA.
|
||
</docAuthorAffiliation>
|
||
</paragraph>
|
||
</footnote>
|
||
</subSubSection>
|
||
<footnote id="4B9A9258D65CFFD7A359F8E4FEADF883" pageId="0" pageNumber="1040">
|
||
<paragraph id="283E8E56D65CFFD7A359F8E4FEADF883" blockId="0.[96,541,1873,1913]" pageId="0" pageNumber="1040">
|
||
*To whom correspondence should be addressed. E-mail:
|
||
<docAuthorEmail id="778EEF41D65CFFD7A359F8D2FEADF883" box="[96,267,1895,1913]" pageId="0" pageNumber="1040">ppevzner@cs.ucsd. edu</docAuthorEmail>
|
||
</paragraph>
|
||
</footnote>
|
||
<paragraph id="283E8E56D65CFFD7A162F8FCFA77FB96" blockId="0.[571,1014,609,1914]" lastBlockId="0.[1045,1489,135,1802]" pageId="0" pageNumber="1040">
|
||
Asara
|
||
<emphasis id="1AF55244D65CFFD7A1A8F8FCFD13F8A4" box="[657,693,1865,1886]" italics="true" pageId="0" pageNumber="1040">et al</emphasis>
|
||
. (
|
||
<bibRefCitation id="4C10F3A7D65CFFD7A1FFF8FCFD77F8A4" author="J. M. Asara" box="[710,721,1865,1886]" journalOrPublisher="Science" pageId="0" pageNumber="1040" pagination="1324" part="317" refId="ref1564" refString="3. J. M. Asara et al., Science 317, 1324 (2007)." type="journal article" year="2007">
|
||
<emphasis id="1AF55244D65CFFD7A1FFF8FCFD77F8A4" box="[710,721,1865,1886]" italics="true" pageId="0" pageNumber="1040">3</emphasis>
|
||
</bibRefCitation>
|
||
) must have generated at least hundreds of thousands of spectra, and their database is much larger than 1000 amino acids. This immediately characterizes the peptide GVVGLP*GQR as a statistical artifact,in addition to GLVGAPGLRGLPGK, which the authors acknowledge in (
|
||
<bibRefCitation id="4C10F3A7D65CFFD7A65CFF6EFAD7FF0A" author="J. M. Asara" box="[1381,1393,219,240]" journalOrPublisher="Science" pageId="0" pageNumber="1040" pagination="1324" part="317" refId="ref1564" refString="3. J. M. Asara et al., Science 317, 1324 (2007)." type="journal article" year="2007">
|
||
<emphasis id="1AF55244D65CFFD7A65CFF6EFAD7FF0A" box="[1381,1393,219,240]" italics="true" pageId="0" pageNumber="1040">3</emphasis>
|
||
</bibRefCitation>
|
||
). If Asara
|
||
<emphasis id="1AF55244D65CFFD7A72CFF42FB98FEF6" box="[1045,1086,247,268]" italics="true" pageId="0" pageNumber="1040">et al</emphasis>
|
||
. (
|
||
<bibRefCitation id="4C10F3A7D65CFFD7A76AFF42FBF8FEF6" author="J. M. Asara & M. H. Schweitzer & L. M. Freimark & M. Phillips & L. C. cantley" box="[1107,1118,247,268]" journalOrPublisher="Science" pageId="0" pageNumber="1040" pagination="280" part="316" refId="ref1497" refString="1. J. M. Asara, M. H. Schweitzer, L. M. Freimark, M. Phillips, L. C. Cantley, Science 316, 280 (2007)." type="journal article" year="2007">
|
||
<emphasis id="1AF55244D65CFFD7A76AFF42FBF8FEF6" box="[1107,1118,247,268]" italics="true" pageId="0" pageNumber="1040">1</emphasis>
|
||
</bibRefCitation>
|
||
) stand by the statistical significance argument given in (
|
||
<bibRefCitation id="4C10F3A7D65CFFD7A782FEA6FB60FED2" author="J. M. Asara" box="[1211,1222,275,296]" journalOrPublisher="Science" pageId="0" pageNumber="1040" pagination="1324" part="317" refId="ref1564" refString="3. J. M. Asara et al., Science 317, 1324 (2007)." type="journal article" year="2007">
|
||
<emphasis id="1AF55244D65CFFD7A782FEA6FB60FED2" box="[1211,1222,275,296]" italics="true" pageId="0" pageNumber="1040">3</emphasis>
|
||
</bibRefCitation>
|
||
), they should question all of the
|
||
<taxonomicName id="EF81F5D5D65CFFD7A701FE9BFBCFFEB9" authority="Osborn, 1905" box="[1080,1129,302,323]" class="Reptilia" family="Tyrannosauridae" genus="Tyrannosaurus" kingdom="Animalia" order="Dinosauria" pageId="0" pageNumber="1040" phylum="Chordata" rank="species" species="rex">
|
||
<emphasis id="1AF55244D65CFFD7A701FE9BFBCFFEB9" box="[1080,1129,302,323]" italics="true" pageId="0" pageNumber="1040">T. rex</emphasis>
|
||
</taxonomicName>
|
||
peptides identified in (
|
||
<bibRefCitation id="4C10F3A7D65CFFD7A678FE9BFAEAFEB9" author="J. M. Asara & M. H. Schweitzer & L. M. Freimark & M. Phillips & L. C. cantley" box="[1345,1356,302,323]" journalOrPublisher="Science" pageId="0" pageNumber="1040" pagination="280" part="316" refId="ref1497" refString="1. J. M. Asara, M. H. Schweitzer, L. M. Freimark, M. Phillips, L. C. Cantley, Science 316, 280 (2007)." type="journal article" year="2007">
|
||
<emphasis id="1AF55244D65CFFD7A678FE9BFAEAFEB9" box="[1345,1356,302,323]" italics="true" pageId="0" pageNumber="1040">1</emphasis>
|
||
</bibRefCitation>
|
||
). Only one of these peptides was supported by chemical synthesis with a spectral correlation coefficient of 0.71, which although borderline significant, may also represent homeometric (
|
||
<bibRefCitation id="4C10F3A7D65CFFD7A622FE2BFA80FE49" author="A. M. Frank & M. M. Savitski & M. L. Nielsen & R. A. Zubarev & P. A. Pevzner" box="[1307,1318,414,435]" journalOrPublisher="J. Proteome Res." pageId="0" pageNumber="1040" pagination="114" part="6" refId="ref1705" refString="6. A. M. Frank, M. M. Savitski, M. L. Nielsen, R. A. Zubarev, P. A. Pevzner, J. Proteome Res. 6, 114 (2007)." type="journal article" year="2007">
|
||
<emphasis id="1AF55244D65CFFD7A622FE2BFA80FE49" box="[1307,1318,414,435]" italics="true" pageId="0" pageNumber="1040">6</emphasis>
|
||
</bibRefCitation>
|
||
), but not identical, peptides. We argue that most of the peptides with GVVGLP*GQR-like spectra (e.g., 10,919 peptides with better InsPecT scores or 10,294 peptides with better X!Tandem scores than GVVGLP*GQR) would have produced spectra that are somewhat similar to the spectrum of GVVGLP*GQR, thus calling for more extensive synthesis-based verification of the results in (
|
||
<bibRefCitation id="4C10F3A7D65CFFD7A630FDC8FAB2FD68" author="J. M. Asara & M. H. Schweitzer & L. M. Freimark & M. Phillips & L. C. cantley" box="[1289,1300,637,658]" journalOrPublisher="Science" pageId="0" pageNumber="1040" pagination="280" part="316" refId="ref1497" refString="1. J. M. Asara, M. H. Schweitzer, L. M. Freimark, M. Phillips, L. C. Cantley, Science 316, 280 (2007)." type="journal article" year="2007">
|
||
<emphasis id="1AF55244D65CFFD7A630FDC8FAB2FD68" box="[1289,1300,637,658]" italics="true" pageId="0" pageNumber="1040">1</emphasis>
|
||
</bibRefCitation>
|
||
). For example, one could potentially synthesize GVVGLP*GQR and discover that the resulting spectrum “looks like” one of the
|
||
<taxonomicName id="EF81F5D5D65CFFD7A7BFFD64FB1DFD1C" authority="Osborn, 1905" box="[1158,1211,721,742]" class="Reptilia" family="Tyrannosauridae" genus="Tyrannosaurus" kingdom="Animalia" order="Dinosauria" pageId="0" pageNumber="1040" phylum="Chordata" rank="species" species="rex">
|
||
<emphasis id="1AF55244D65CFFD7A7BFFD64FB1DFD1C" box="[1158,1211,721,742]" italics="true" pageId="0" pageNumber="1040">T. rex</emphasis>
|
||
</taxonomicName>
|
||
spectra, thus “proving” that GVVGLP*GQR is indeed a
|
||
<taxonomicName id="EF81F5D5D65CFFD7A612FD58FAC6FCF8" authority="Osborn, 1905" box="[1323,1376,749,770]" class="Reptilia" family="Tyrannosauridae" genus="Tyrannosaurus" kingdom="Animalia" order="Dinosauria" pageId="0" pageNumber="1040" phylum="Chordata" rank="species" species="rex">
|
||
<emphasis id="1AF55244D65CFFD7A612FD58FAC6FCF8" box="[1323,1376,749,770]" italics="true" pageId="0" pageNumber="1040">T. rex</emphasis>
|
||
</taxonomicName>
|
||
peptide. In this case, it is puzzling how Asara
|
||
<emphasis id="1AF55244D65CFFD7A66DFCBCFADDFCE4" box="[1364,1403,777,798]" italics="true" pageId="0" pageNumber="1040">et al</emphasis>
|
||
. selected the “correct” statistically insignificant peptide among hundreds of other statistically insignificant peptides. For example, peptides RVGLRAAR, RVGLPTKK, RVGP*PTKK, and thousands of others represent better InsPecTand X!Tandem spectral interpretations than GVVGLP*GQR (table S1) (supporting online material). If one is willing to argue that GVVGLP*GQR is a valid identification based on peptide synthesis, the peptides RVGLRAAR, RVGLPTKK, and RVGP*PTKK should also be synthesized and compared to the
|
||
<taxonomicName id="EF81F5D5D65CFFD7A679FB89FAD6FBAB" authority="Osborn, 1905" box="[1344,1392,1084,1105]" class="Reptilia" family="Tyrannosauridae" genus="Tyrannosaurus" kingdom="Animalia" order="Dinosauria" pageId="0" pageNumber="1040" phylum="Chordata" rank="species" species="rex">
|
||
<emphasis id="1AF55244D65CFFD7A679FB89FAD6FBAB" box="[1344,1392,1084,1105]" italics="true" pageId="0" pageNumber="1040">T. rex</emphasis>
|
||
</taxonomicName>
|
||
spectrum. Extraordinary science requires extraordinary proofs.
|
||
</paragraph>
|
||
<paragraph id="283E8E56D65CFFD7A70CFBC6FA76FA9D" blockId="0.[1045,1489,135,1802]" pageId="0" pageNumber="1040">
|
||
Since the publication of their report (
|
||
<bibRefCitation id="4C10F3A7D65CFFD7A647FBC6FA2FFB72" author="J. M. Asara & M. H. Schweitzer & L. M. Freimark & M. Phillips & L. C. cantley" box="[1406,1417,1139,1160]" journalOrPublisher="Science" pageId="0" pageNumber="1040" pagination="280" part="316" refId="ref1497" refString="1. J. M. Asara, M. H. Schweitzer, L. M. Freimark, M. Phillips, L. C. Cantley, Science 316, 280 (2007)." type="journal article" year="2007">
|
||
<emphasis id="1AF55244D65CFFD7A647FBC6FA2FFB72" box="[1406,1417,1139,1160]" italics="true" pageId="0" pageNumber="1040">1</emphasis>
|
||
</bibRefCitation>
|
||
), Asara
|
||
<emphasis id="1AF55244D65CFFD7A72CFB3AFB98FB5E" box="[1045,1086,1167,1188]" italics="true" pageId="0" pageNumber="1040">et al</emphasis>
|
||
. have reinterpreted (
|
||
<bibRefCitation id="4C10F3A7D65CFFD7A7C4FB3AFAAEFB5E" author="J. M. Asara" box="[1277,1288,1167,1188]" journalOrPublisher="Science" pageId="0" pageNumber="1040" pagination="1324" part="317" refId="ref1564" refString="3. J. M. Asara et al., Science 317, 1324 (2007)." type="journal article" year="2007">
|
||
<emphasis id="1AF55244D65CFFD7A7C4FB3AFAAEFB5E" box="[1277,1288,1167,1188]" italics="true" pageId="0" pageNumber="1040">3</emphasis>
|
||
</bibRefCitation>
|
||
) four out of seven of the
|
||
<taxonomicName id="EF81F5D5D65CFFD7A701FB1EFBCFFB3A" authority="Osborn, 1905" box="[1080,1129,1195,1216]" class="Reptilia" family="Tyrannosauridae" genus="Tyrannosaurus" kingdom="Animalia" order="Dinosauria" pageId="0" pageNumber="1040" phylum="Chordata" rank="species" species="rex">
|
||
<emphasis id="1AF55244D65CFFD7A701FB1EFBCFFB3A" box="[1080,1129,1195,1216]" italics="true" pageId="0" pageNumber="1040">T. rex</emphasis>
|
||
</taxonomicName>
|
||
peptides originally reported. The most likely outcome of further criticism is that Asara and colleagues will continue changing their original interpretations until the critics give up. So far, five out of six of the remaining significant
|
||
<taxonomicName id="EF81F5D5D65CFFD7A6A4FAAEFA68FACA" authority="Osborn, 1905" box="[1437,1486,1307,1328]" class="Reptilia" family="Tyrannosauridae" genus="Tyrannosaurus" kingdom="Animalia" order="Dinosauria" pageId="0" pageNumber="1040" phylum="Chordata" rank="species" species="rex">
|
||
<emphasis id="1AF55244D65CFFD7A6A4FAAEFA68FACA" box="[1437,1486,1307,1328]" italics="true" pageId="0" pageNumber="1040">T. rex</emphasis>
|
||
</taxonomicName>
|
||
peptides have already emerged as identical to chicken peptides. Maybe
|
||
<taxonomicName id="EF81F5D5D65CFFD7A7F3FAE7FB5FFA9D" authority="Osborn, 1905" box="[1226,1273,1362,1383]" class="Reptilia" family="Tyrannosauridae" genus="Tyrannosaurus" kingdom="Animalia" order="Dinosauria" pageId="0" pageNumber="1040" phylum="Chordata" rank="species" species="rex">
|
||
<emphasis id="1AF55244D65CFFD7A7F3FAE7FB5FFA9D" box="[1226,1273,1362,1383]" italics="true" pageId="0" pageNumber="1040">T. rex</emphasis>
|
||
</taxonomicName>
|
||
was a chicken after all?
|
||
</paragraph>
|
||
<paragraph id="283E8E56D65CFFD7A70CFADBFA80F8F0" blockId="0.[1045,1489,135,1802]" pageId="0" pageNumber="1040">
|
||
Recently, a group of 27 mass spectrometrists, bioinformaticians, and dinosaur experts published an insightful criticism of the
|
||
<taxonomicName id="EF81F5D5D65CFFD7A629FA13FA99FA41" authority="Osborn, 1905" box="[1296,1343,1446,1467]" class="Reptilia" family="Tyrannosauridae" genus="Tyrannosaurus" kingdom="Animalia" order="Dinosauria" pageId="0" pageNumber="1040" phylum="Chordata" rank="species" species="rex">
|
||
<emphasis id="1AF55244D65CFFD7A629FA13FA99FA41" box="[1296,1343,1446,1467]" italics="true" pageId="0" pageNumber="1040">T. rex</emphasis>
|
||
</taxonomicName>
|
||
protein analysis (
|
||
<bibRefCitation id="4C10F3A7D65CFFD7A724FA77FB8EFA2D" author="M. Buckley" box="[1053,1064,1474,1495]" journalOrPublisher="Science" pageId="0" pageNumber="1040" pagination="33" part="319" publicationUrl="www.sciencemag.org/cgi/content/full/319/5859/33c" refId="ref1749" refString="7. M. Buckley et al., Science 319, 33 (2008); www. sciencemag. org / cgi / content / full / 319 / 5859 / 33 c." type="journal article" year="2008">
|
||
<emphasis id="1AF55244D65CFFD7A724FA77FB8EFA2D" box="[1053,1064,1474,1495]" italics="true" pageId="0" pageNumber="1040">7</emphasis>
|
||
</bibRefCitation>
|
||
). Still, Asara and Schweitzer (
|
||
<bibRefCitation id="4C10F3A7D65CFFD7A669FA77FAFDFA2D" author="J. M. Asara & M. H. Schweitzer" box="[1360,1371,1474,1495]" journalOrPublisher="Science" pageId="0" pageNumber="1040" pagination="33" part="319" publicationUrl="www.sciencemag.org/cgi/content/full/319/5859/33d" refId="ref1785" refString="8. J. M. Asara, M. H. Schweitzer, Science 319, 33 (2008); www. sciencemag. org / cgi / content / full / 319 / 5859 / 33 d." type="journal article" year="2008">
|
||
<emphasis id="1AF55244D65CFFD7A669FA77FAFDFA2D" box="[1360,1371,1474,1495]" italics="true" pageId="0" pageNumber="1040">8</emphasis>
|
||
</bibRefCitation>
|
||
), refused to acknowledge the problems with their analysis. It is now the turn of the mass spectrometry community to question whether the monkey can actually spell. It is very easy to check; just ask the boy how many words (e.g., spectra) the monkey has generated and what tests of statistical significance were used to compute FPR. With this information in hand, the scientists can finally match all dinosaur proteins against Webster’ s dictionary to see whether mass spectrometers can spell and whether
|
||
<taxonomicName id="EF81F5D5D65CFFD7A75CF940FB30F8F0" authority="Osborn, 1905" box="[1125,1174,1781,1802]" class="Reptilia" family="Tyrannosauridae" genus="Tyrannosaurus" kingdom="Animalia" order="Dinosauria" pageId="0" pageNumber="1040" phylum="Chordata" rank="species" species="rex">
|
||
<emphasis id="1AF55244D65CFFD7A75CF940FB30F8F0" box="[1125,1174,1781,1802]" italics="true" pageId="0" pageNumber="1040">T. rex</emphasis>
|
||
</taxonomicName>
|
||
was a chicken.
|
||
</paragraph>
|
||
</subSubSection>
|
||
</treatment>
|
||
</document> |