Microbial Proteomics: Functional Biology of Whole Organisms by Ian Humphery-SmithMicrobial Proteomics: Functional Biology of Whole Organisms by Ian Humphery-Smith

Microbial Proteomics: Functional Biology of Whole Organisms

EditorIan Humphery-Smith, Michael Hecker

Hardcover | August 11, 2006

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Discover important lessons learned about whole organism biology via microbial proteomics

This text provides an exhaustive analysis and presentation of current research in the field of microbial proteomics, with an emphasis on new developments and applications and future directions in research. The editors and authors show how and why the relative simplicity of microbes has made them attractive targets for extensive experimental manipulation in a quest for both improved disease prevention and treatment and an improved understanding of whole organism functional biology. In particular, the text demonstrates how microbial proteomic analyses can aid in drug discovery, including identification of new targets, novel diagnostic markers, and lead optimization.

Each chapter is written by one or more leading experts in the field and carefully edited to ensure a consistent and thorough approach throughout. Methods, technologies, and tools associated with the most promising approaches are stressed. Key topics covered include:

  • Microbial pathogenesis at the proteome level
  • Whole cell modeling
  • Structural proteomics and computational analysis
  • Biomolecular interactions
  • Physiological proteomics
  • Metabolic reconstruction using proteomics data

While presenting the practical utility of proteomics data, the text is also clear on the field's current limitations, pointing to areas where further investigation is needed.

Offering a state-of-the-art perspective from internationally recognized experts, this text is ideally suited for researchers and students across the gamut of genomic sciences, including biochemistry, microbiology, molecular biology, genetics, biomedical and pharmaceutical sciences, biotechnology, and veterinary science.

IAN HUMPHERY-SMITH, PHD, is the Founding Chair of the Department of Pharmaceutical Proteomics at Utrecht University. Dr. Humphery-Smith has served as director of the Centre for Proteome Research and Gene-Product Mapping and served as managing director and chief scientific officer of Glaucus Proteomics BV. MICHAEL HECKER, PHD, is Profe...
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Title:Microbial Proteomics: Functional Biology of Whole OrganismsFormat:HardcoverDimensions:538 pages, 10.3 × 7.2 × 1.25 inPublished:August 11, 2006Publisher:WileyLanguage:English

The following ISBNs are associated with this title:

ISBN - 10:0471699756

ISBN - 13:9780471699750

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452.604 71.414 14.089 re S BT 7.7725 0 0 7.7725 298.0483 457.4738 Tm 0 Tw (Detection)Tj ET 1 g 359.734 487.096 71.414 14.089 re B* BT 7.7725 0 0 7.7725 386.9521 491.9662 Tm 0 g (2DE)Tj ET 1 J 395.685 517.703 m 395.685 501.185 l 294.15 535.677 m 297.065 535.677 l 297.065 541.507 l 300.465 541.507 l 299.008 504.585 m 299.008 512.844 l 294.15 512.844 l 294.15 521.589 l 343.217 493.412 m 351.476 493.412 l 351.476 489.525 l 359.734 489.525 l 294.15 490.983 m 294.15 478.837 l 314.068 478.837 l 314.068 466.692 l 395.685 487.096 m 395.685 476.894 l 314.068 476.894 l 314.068 466.692 l 177.069 517.703 m 177.069 459.405 l 278.604 459.405 l S 0 J 133.346 414.225 94.733 14.088 re S BT 7.7725 0 0 7.7725 142.1028 419.095 Tm 0.0001 Tc 0.0024 Tw [(Non-MS-based anal)20.1(ysis)]TJ ET 254.799 414.225 88.418 14.088 re S BT 7.7725 0 0 7.7725 268.4137 419.095 Tm [(MS-based anal)20(ysis)]TJ ET 1 g 363.135 440.944 44.695 14.089 re B* 363.135 414.225 45.667 14.088 re B* BT 7.7725 0 0 7.7725 377.2354 419.095 Tm 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[(A)50(utomation)]TJ ET 214.477 594.46 77.73 14.575 re S BT 7.7725 0 0 7.7725 234.097 599.3304 Tm [(Meta)10(bolites)]TJ ET 1 J 251.398 616.322 m 251.398 609.035 l S 1 g 0 J 149.864 559.968 44.209 14.089 re B* 194.073 559.968 40.808 14.089 re B* 1 J 270.345 616.322 m 270.345 632.84 l 192.615 363.7 m 192.615 355.441 l S 0 J 245.083 490.983 98.134 14.088 re B* BT 7.7725 0 0 7.7725 264.0021 495.8529 Tm 0 g 0.0324 Tw [(2D Chr)30(omato)10(gr)10(aph)45(y)]TJ ET 1 J 238.282 526.447 m 245.083 526.933 l S BT 7.7725 0 0 7.7725 243.1516 358.8542 Tm 0 Tw [(Bioinf)25(ormatics)]TJ ET 301.552 559.968 m 301.066 550.252 l S EMC BT /F7 1 Tf 8.9663 0 0 8.9663 91.6724 325.7007 Tm /GS2 gs [(Figure)-428(1.2)]TJ /F6 1 Tf 5.5199 0 TD [(Schematic)-432.8(of)-418.9(integrati)12.4(on)-429(of)-431.6(technologies)-432(for)-427.4(proteomics.)-429.3(The)-430.7(uni)]TJ /F3 1 Tf 27.4009 0 TD ()Tj /F6 1 Tf 0.552 0 TD [(cation)-421.6(of)-431.6(DN)32.3(A,)]TJ -33.4728 -1.2203 TD [(mRN)34.2(A,)-593.8(and)-589(metabolite)-597.4(information)-587(is)-592.3(essential)-599(for)-585.5(a)-596.3(complete)-590.4(understanding)-592.1(of)-589.7(biological)]TJ 0 -1.2266 TD [(function)-331.7([58].)]TJ /F11 1 Tf 0 40.8207 TD (6)Tj /F12 1 Tf 6.9738 0 0 6.9738 113.896 669.7699 Tm [(HOLIST)-13.6(IC)-399.3(BIOL)44.5(OGY)-340.9(OF)-401.6(MICROORGANISMS)]TJ ET endstream endobj 17 0 obj > endobj 18 0 obj > endobj 19 0 obj > /ExtGState > >> endobj 20 0 obj > stream BT /F6 1 Tf 9.9626 0 0 9.9626 53.8016 639.3258 Tm 0 g /GS2 gs 0 Tc 0 Tw [(greates)-10.9(t)-339.3(separat)-10.9(ion)-340.8(po)15.5(wer)-345.7(for)-342(highly)-345.8(com)-7.6(ple)10.2(x)-342.2(sample)-9.9(s.)-343.8(The)-345.3(expa)10.5(n)-6.5(sion)-342.7(of)-339.2(p)-6.5(H)-340.4(separat)-10.9(ion)]TJ 0 -1.2007 TD [(using)-457.3(a)-452.1(series)-459.1(of)-453.1(ov)21.2(erlapping)-461.8(narro)18.9(w-)-7.4(range)-441.8(g)-6.5(els)-451.9(to)-453.8(assemble)-458.3(a)-452.1(cont)-7.6(iguou)-6.6(s)-451.5(collage)-460(of)]TJ T* [(protei)-8.1(n)-234.1(expression)-234.5(and)-237.4(allo)12.4(w)-238(for)-233.9(a)-241.6(more)-237.9(meticul)-9.3(ous)-236.8(analysi)-9.9(s)-235.3(o)0(f)-236.8(proteom)-9.7(es)-237.8(was)-236.8(est)-8(ablished)]TJ T* [(in)-237.6(1997)-236.3(for)]TJ /F4 1 Tf 4.6606 0 TD [(O.)-238.4(anthr)37.8(opi)]TJ /F6 1 Tf 4.854 0 TD [([22])-240.3(and)]TJ /F4 1 Tf 3.5907 0 TD [(M.)-237.2(geni)-7.6(talium)]TJ /F6 1 Tf 5.6223 0 TD [(.)-233.7(Close)-241.9(to)-237.6(two-t)-9.5(hirds)-237.3(of)]TJ /F4 1 Tf 9.452 0 TD [(M.)-237.2(geni)-7.6(talium)]TJ /F6 1 Tf 5.8556 0 TD (open)Tj -34.0352 -1.2007 TD [(reading)-224.2(fra)-8(mes)-219.3(\(ORFs)-9.1(\))-219(were)-223.1(sho)19.3(wn)-221.7(to)-220.5(be)-219.5(expressed)-221.4(using)-218.3(this)-226(approach)-223.9([2].)-222.8(This)-223(appro)-7.5(ach)]TJ T* [(is)-455(no)21.2(w)-454.3(common)-7.7(ly)-453.8(used)-455.6(and)-453.6(bacterial)-462.4(examples)-451.4(include)]TJ /F4 1 Tf 23.7922 0 TD [(Spir)38.5(oplas)-7.7(ma)-455(melliferum)]TJ /F6 1 Tf 10.2771 0 TD ([23],)Tj /F4 1 Tf -34.0693 -1.2007 TD [(Mycoba)-10.8(cterium)-315.4(tuber)24.6(culosis)]TJ /F6 1 Tf 11.7908 0 TD [([24])-7(,)]TJ /F4 1 Tf 2.2307 0 TD [(Coryneb)-9.1(acteri)-9.1(um)-307.1(glutam)-8.3(icum)]TJ /F6 1 Tf 12.3769 0 TD [([25],)-309(and)]TJ /F4 1 Tf 3.9834 0 TD [(Str)27.9(epto)-7.6(coccus)]TJ -30.3818 -1.2007 TD (mutans)Tj /F6 1 Tf 3.1924 0 TD ([26].)Tj -1.9917 -1.195 TD [(Proteom)-8.9(ics)-588.5(is)-585.9(also)-589.2(providing)-583.4(practical)-593.3(appl)-7.6(ications)-593.9(through)-590.5(the)-587.3(iden)-7.6(ti)]TJ /F3 1 Tf 30.3634 0 TD ()Tj /F6 1 Tf 0.552 0 TD [(cation)-584(of)]TJ -32.1161 -1.2007 TD [(immu)-7.1(nogenic)-205.1(prot)-7.8(eins)-202.3(as)-203.7(p)-6.5(otential)-208.5(v)22(accine)-213.6(targets.)-194.4(Many)-200.2(hypot)-6.5(heses)-203.2(gener)-9.3(ated)-208.5(in)-203.5(silico)-203.6(by)]TJ T* [(genomic)-9.5(s)-571(hav)18.7(e)-565.9(b)-6.5(een)-540.8(v)22(alidated)-577.4(through)-573.4(functi)-8.1(onal)-570.9(stud)-7(ies)-571.4(of)-566.9(the)-570.2(tra)-8.8(nscriptom)-9.4(e)-565.9(and)]TJ T* [(proteom)-9.7(e)-287.1(and)-288.6(hav)18.7(e)-287.1(led)-291.4(to)-288.8(the)-285.7(iden)-7.6(ti)]TJ /F3 1 Tf 14.3844 0 TD ()Tj /F6 1 Tf 0.552 0 TD [(cation)-282.4(of)-288(esse)-9(ntial)-287(genes)-8.5(.)-284.9(Using)-290.5(2DE)-290.5([27])-291.5(and)-288.6(DN)24.8(A)]TJ -14.9364 -1.2007 TD [(micro)-8.1(arrays)-320.5([28])-314.3(for)-313.5(dif)15.7(ferential)-320.3(expression)-314.2(analysi)-9.9(s)-314.9(has)-312.5(con)]TJ /F3 1 Tf 24.5791 0 TD ()Tj /F6 1 Tf 0.552 0 TD [(rmed)-315.9(that)-311.9(the)-319.8(resistanc)-10.7(e)-315.5(o)0(f)]TJ /F4 1 Tf -25.1311 -1.2007 TD [(M.)-413.6(tuber)24.6(culosis)]TJ /F6 1 Tf 6.7831 0 TD [(to)-414(the)-410.9(anti-t)-10.9(uberculo)-8.7(sis)-411.5(cel)-8.6(l)-407.6(e)0(n)25.1(vel)10.3(ope)-419.5(drug)-414.7(isoniazid)-418.2(was)-418.9(the)-416.6(result)-419.1(of)]TJ -6.7831 -1.2007 TD [(ov)21.2(erexpression)-239.8(of)-242.5(component)-11(s)-235.3(o)0(f)-236.8(the)-240.1(fatty)-240.7(aci)-8.6(d)-234.1(synt)-7(hase)-241.1(system,)-243(in)-237.6(partic)-9.9(ular)-237.2(Acp)-8(M)-236(and)-237.4(a)]TJ T* [(carrier)-264(protein)-259.3(synthase)-259.5(KasA.)-258.9(A)-255.1(com)-7.6(pilation)-257.9(of)]TJ /F4 1 Tf 19.5926 0 TD [(M.)-254.3(tube)-7.6(r)32.2(culo)-7.6(sis)]TJ /F6 1 Tf 6.4645 0 TD [([29])-257.4(and)]TJ /F4 1 Tf 3.6306 0 TD [(Mycobacteri)-13.5(um)]TJ -29.6876 -1.195 TD (bovis)Tj /F6 1 Tf 2.3274 0 TD [([30])-211.8(induced)-216.5(immunore)-8.2(sponse)-8.7(s)-206.8(i)0(n)-209.1(spleno)-10.3(cyt)10.2(es)-209.4(usin)-7(g)-205.6(2)0(D)-216(liquid-pha)-8.2(se)-209.4(elect)-9(rophoresis)]TJ -2.3274 -1.2007 TD [(has)-244.3(also)-242.1(identi)]TJ /F3 1 Tf 5.7215 0 TD ()Tj /F6 1 Tf 0.552 0 TD [(ed)-234.1(multipl)-8.5(e)-241.6(antigen)-8.7(s)-235.3(assoc)-9.7(iated)-240.5(with)-245.8(posttransl)-10.6(ationall)-9.3(y)-234.1(modi)]TJ /F3 1 Tf 24.501 0 TD ()Tj /F6 1 Tf 0.5406 0 TD [(ed)-242.3(proteins.)]TJ -31.3151 -1.2007 TD [(In)-231.1(1999,)-236.7(Jungblut)-234.7(et)-233.7(al.)-234.1([31])-234.6(com)-7.6(pared)-237(the)-234.4(proteomes)-241.8(of)-231.1(two)-230.9(no)-7.2(n)33.4(virule)-8.1(nt)-231.9(v)22(accine)-242.1(strains)-238.9(of)]TJ /F4 1 Tf T* [(M.)-299.8(bovi)-7.6(s)]TJ /F6 1 Tf 3.8013 0 TD [(BCG)-305.9(with)-308.4(two)-293.5(virulent)-302.6(strai)-8.6(ns)-298.6(of)]TJ /F4 1 Tf 13.7199 0 TD [(M.)-299.8(tube)-7.6(r)32.2(culo)-7.6(sis)]TJ /F6 1 Tf 6.5555 0 TD [(to)-305.9(identify)-308.3(protein)-304.8(candidat)-11.2(es)]TJ -24.0767 -1.2007 TD [(for)-222.5(potential)-226.3(v)16.3(accine)-225(de)13.8(vel)10.2(opme)-8.3(nt)-220.5(as)-220.7(well)-224.8(as)-220.7(for)-222.5(diag)-7.6(nostic)-223.6(and)-226(therape)-9.7(utic)-220.9(purpos)-7.7(es.)-221.1(Over)]TJ T* [(30)-331.6(dif)21.4(fer)-8(ences)-334.7(were)-331.2(iden)-7.6(ti)]TJ /F3 1 Tf 10.6798 0 TD ()Tj /F6 1 Tf 0.552 0 TD [(ed)-323.3(among)-333.5(the)-331.2(strai)-8.6(ns,)-327.4(includi)-9.7(ng)-331.6(three)-336.5(cell)-330.8(en)30.8(velope)-329.6(proteins,)]TJ -11.2318 -1.2007 TD [(some)-242.8(antigen)-8.7(ic)-245.1(protei)-8.1(ns,)-242.1(and)-243.1(nov)20.5(el)-245.1(unannot)-9.8(ated)-242.7(protei)-8.1(ns.)-242.1(This)-245.8(work,)-242.6(as)-243.5(well)-247.6(as)-243.5(work)-242.2(from)]TJ T* [(others,)-445.1(has)-443.4(contributed)-437.6(to)-436.8(a)-440.7(better)-442.4(under)-7.5(standin)-8.1(g)-438.9(o)0(f)-436(the)-445(pathogeni)-10.2(c)-440.7(and)-436.6(physi)-7.7(ologica)-8.7(l)]TJ 0 -1.195 TD [(mechani)-11.2(sm)-376.1(av)25.1(ailable)-383.1(to)-379.9(this)-385.3(orga)10.3(nism)-386.1(and)-379.6(also)-384.4(contributed)-375(to)-379.9(the)-382.4(de)19.5(velopment)-377.9(of)-379.1(n)-6.5(e)20.2(w)]TJ 0 -1.2007 TD [(v)22(accine)-253.5(candidat)-11.2(es.)]TJ /F4 1 Tf 8.0407 0 TD [(Myc)-8.6(obacterium)-255.1(bovis)]TJ /F6 1 Tf 8.9114 0 TD [(BCG)-248.9(\(li)18.7(ve)-236.6(attenuate)-10.9(d\))-242.5(has)-249.9(been)-245.6(the)-245.8(only)-250.5(widely)]TJ -16.9521 -1.2007 TD [(used)-319(v)16.3(accine)-321.7(av)30.8(ailabl)-10.7(e)-315.5(against)-322.9(tube)-7.6(rculosis)-319.3(unti)-8.6(l)-310.8(rece)-10.4(ntly)59.7(,)-313.4(with)-319.8(ne)13.8(w)-317.7(tuberculosi)-12(s)-314.9(v)22(accine)]TJ T* [(trials)-308(begun)-295.8(in)-300.2(2004.)]TJ 1.2007 -1.2007 TD [(T)73.4(wo-dim)-11(ensional)-460.2(gel)-450.7(ele)-8.6(ctrophor)-8.9(esis)-453.8(is)-455(a)-452.1(p)0(o)21.2(werful)-460.8(protei)-8.1(n)-450.3(separat)-10.9(ion)-454.6(techniqu)-9.5(e)-452.1(i)0(n)]TJ -1.2007 -1.2007 TD [(combina)-9.5(tion)-361.4(with)-365.3(MS,)-367.3(yet)-365.3(it)-359.9(does)-364.5(not)-363.5(always)-368.8(deli)12.4(ver)-353.2(the)-359.6(appro)-7.6(priate)-368.4(sensit)-8.5(i)19.2(vity)-361.4(for)-364.7(the)]TJ T* [(discov)12.5(ery)-296.3(of)-299.4(lo)18.5(w-le)15(vel)-291.3(protei)-8.1(ns)-298.6([32],)-297.6(protei)-8.1(ns)-298.6(with)-302.7(ext)10.3(reme)-302.3(isoe)-8.8(lectric)-305.5(point)-299.5(\(pI\))-299.2(or)-299.4(mass)]TJ T* [([11],)-229.3(or)-225.4(membrane-)-11.8(associa)-10.1(ted)-223.1(prot)-7.8(eins)-225(becau)-9.1(se)-226.4(of)-225.4(solubility)-227.4(iss)-7.4(ues)-227.2([33].)-223.6(For)-219.7(these)-227.6(reasons,)]TJ 0 -1.195 TD [(the)-826.3(de)19.5(velopment)-827.5(of)-828.6(alternat)-10.3(i)24.9(v)0(e)-817.1(appro)-7.6(aches)-829.8(to)-829.4(2DE,)-831.5(such)-825.4(as)-829.6(multidi)-8.5(mensio)-8.1(nal)]TJ 0 -1.2007 TD [(chromat)-11.4(ography)-589.5(coupled)-592.1(to)-584.7(MS)-8.4(,)-580.8(has)-591.4(been)-558.6(vital)-588.6(to)-584.7(the)-593(success)-594.7(of)]TJ /F4 1 Tf 29.5283 0 TD (Bidobacterium)Tj /F6 1 Tf -29.5283 -1.2007 TD [(proteom)-9.7(ics.)]TJ /F4 1 Tf 5.1272 0 TD [(Bi)12.2(do)-7.2(bacterium)]TJ /F6 1 Tf 6.8628 0 TD [(is)-409.5(a)-412.3(gram-p)-8.1(ositi)20.9(ve)-401.6(proka)-7.5(ryote)-408.7(that)-414.4(natural)-10.7(ly)-408.3(coloniz)-8.7(es)-408.5(the)]TJ -11.99 -1.2007 TD [(human)-697.6(gut)-693.6(ex)13.8(erting)-696.7(health-)-10.7(promoting)-700.7(ef)17.5(fects.)-696.5(Clin)-7.6(ical)-695(studies)-697.9(hav)13(e)-691.1(claim)-10.7(ed)-691.9(that)]TJ T* (bi)Tj /F3 1 Tf 0.781 0 TD ()Tj /F6 1 Tf 0.552 0 TD [(dobacterial)-365.7(probiot)-7.1(ics)-360.8(p)-6.5(romote)-356(gastroint)-8.7(estinal)-365.5(tract)-367.7(home)-8.3(ostasis)-363.3(and)-368.3(health)-366.5(becau)-9.1(se)]TJ -1.333 -1.2007 TD [(of)-424.6(antidiarr)-11.2(heal,)-425.2(immu)-7.1(nomod)-7.3(ulating,)-425.5(and)-425.2(possi)-8.9(bly)-426.1(anticarcinoge)-12(nic)-427.9(prope)-7.6(rties.)-424.4(Prot)-7(eo-)]TJ T* [(mics)-774.8(has)-779.2(contributed)-767.6(to)-778.2(the)-769.4(com)-7.6(prehensi)12.9(ve)-765.8(understa)-9.9(nding)-774.8(of)-771.7(the)-775.1(physi)-7.7(ological)]TJ T* [(mechani)-11.2(sms)-298.4(under)-7.5(lying)-299.5(these)-301.5(prope)-7.5(rties)-298.8([34])-7(.)-296.3(A)-294.9(predo)-7.6(minant)-299.9(port)-7.8(ion)-295.3(of)]TJ /F4 1 Tf 29.5283 0 TD (Bidobacterium)Tj -29.5283 -1.195 TD [(infant)-7.1(is)]TJ /F6 1 Tf 3.2778 0 TD [(proteome)-268.3(consist)-9.3(s)-258(o)0(f)-265.3(enzymes)-271.4(of)-259.6(the)-251.5(glyc)-7.6(olytic)-265(and)-265.8(pentose-)-9.9(phosphate)-270.4(pathways,)]TJ -3.2778 -1.2007 TD [(enzymes)-527.5(of)-515.6(anaer)-11.1(obic)-519.7(metabo)-8.7(lism,)-520.1(transcr)-11.1(iptional)-525.3(factors,)-523.6(shock)-524.6(proteins,)-523.4(ribosom)-9.1(al)]TJ T* [(protei)-8.1(ns,)-304.7(and)-311.4(prot)-7.8(eases.)-313.5(The)-311.2(high)-307.4(le)16.7(vel)-302.7(of)-305.1(thes)-8.8(e)-304.2(prot)-7.8(eins)-310.4(during)-310.9(the)-314.1(exponential)-306.5(phase)-315.8(of)]TJ T* [(gro)18.5(wth)-316.3(under)-7.5(lines)-319.6(their)-320.4(central)-325.5(role)-316.9(in)-317.3(cell)-319.4(survi)18.7(v)22(al,)-319.4(replic)-9.9(ation,)-318.8(and)-317(energy)-311.7(metabo)-8.7(lism,)]TJ T* [(gi)18.5(ving)-421.2(an)-424.4(indicat)-11.5(ion)-420.5(of)-424.6(the)-422.2(basal)-426.7(functi)-8.1(ons,)-424.9(which)-427.7(are)-423.2(essential)-432.6(for)-421.6(the)-405.2(vitality)-425.7(of)-424.6(the)]TJ T* (bi)Tj /F3 1 Tf 0.781 0 TD ()Tj /F6 1 Tf 0.552 0 TD [(dobacteria)-305.3(biologi)-7.9(cal)-304.5(system.)]TJ -0.1323 -1.2007 TD [(A)-824.1(uni)]TJ /F3 1 Tf 2.8232 0 TD ()Tj /F6 1 Tf 0.552 0 TD [(cation)-821(of)-822.9(g)-6.5(enomics,)-830.5(transcrip)-9.7(tomics,)-830.7(and)-823.5(prot)-7.8(eomics)-829.3(will)-823.3(provide)-819.9(a)]TJ -4.5759 -1.2007 TD [(compreh)-8.7(ensi)14(ve)-424.4(kno)20.5(wledge)-441.6(base)-434.6(of)-436(gene)-439.1(function)-436.5(and)-436.5(a)-435(p)0(o)21.2(werful)-443.8(reference)-442.8(of)-436(protein)]TJ /F12 1 Tf 6.9738 0 0 6.9738 181.4173 669.7699 Tm [(AMAL)50.6(GAMA)52(TION)-402.5(OF)-401.6(T)44.9(OOLS)-398.6(FOR)-407.1(A)-399(PRO)43.3(TEOMIC)]TJ /F2 1 Tf 23.9086 0 TD ()Tj /F12 1 Tf 0.436 0 TD [(T)50.1(OOL)-406.1(BO)40.6(X)]TJ /F2 1 Tf 5.1564 0 TD ()Tj /F11 1 Tf 8.9663 0 0 8.9663 407.3952 669.7699 Tm (7)Tj ET endstream endobj 21 0 obj > endobj 22 0 obj > /ExtGState > >> endobj 23 0 obj > stream BT /F6 1 Tf 9.9626 0 0 9.9626 91.6724 639.3258 Tm 0 g /GS2 gs 0 Tc 0 Tw [(propert)-8.1(ies.)-355.5(There)-362(are,)-361(ho)15.5(we)21.2(ver)33.8(,)-353.2(signi)]TJ /F3 1 Tf 15.0865 0 TD ()Tj /F6 1 Tf 0.552 0 TD [(cant)-355.6(challe)-9.7(nges)-358.8(that)-357.5(are)-360.6(being)-361.2(addresse)-10.1(d)-353.6(but)-352.2(may)]TJ -15.6385 -1.2007 TD [(remain)-619.6(unresolved)-614.6(until)-615.3(technol)-8.7(ogical)-622.5(adv)18.7(ances)-619.2(can)-614.7(ov)15.5(ercome)-618.6(them.)-620.4(The)-607.1(goal)-616.5(of)]TJ T* [(decipher)-10.5(ing)-642.4(the)-649.9(entire)-653(protein)-651.9(compleme)-9.8(nt)-647.3(of)-646.5(an)-646.3(or)13.6(g)-6.5(anism)-650.4(and)-647.1(making)-650(heuristic)]TJ T* [(relations)-10.5(hips)-291.5(is)-290(formi)-8.3(dable)-294.7(and)-294.3(often)-294.8(limited)-294.8(by)-291.7(cell)-296.7(dynamics.)-296.3(Unde)-8.7(rstanding)-296.1(biologi)-7.9(cal)]TJ T* [(e)20.2(vents)-715.2(such)-728.7(as)-721.5(modi)]TJ /F3 1 Tf 9.4406 0 TD ()Tj /F6 1 Tf 0.5406 0 TD [(cation,)-731(complexity)62.4(,)-723.1(e)0(n)30.8(vironm)-7.1(ental)-724.2(input)-9.3(,)-717.4(and)-726.8(tech)-9.4(nological)]TJ -9.9812 -1.2007 TD [(constra)-9.1(ints)-351.2(of)-350.6(detect)-9.7(ion)-352.2(thresholds)-360.7(and)-351.2(bioinfo)-7.1(rmatics)-356.8(will)-356.7(be)-350.4(require)-9.9(d)-347.9(t)0(o)-351.4(o)0(v)21.2(erco)-8.6(me)-354(the)]TJ T* [(challenges)-311.6(for)-302.1(a)-304.2(complete)-310.7(proteome)-308.1(study)-303.6([1,)-305.5(35].)]TJ /F11 1 Tf 0 -3.5964 TD [(1.4)-1005(RELAT)-10.3(IONSHI)-9.1(P)-335.5(BETWEEN)-348.3(GENOME)-10.6(,)-333.6(TRAN)-8.9(SCRIPTO)-11.6(ME,)]TJ 0 -1.2007 TD [(AND)-338.4(PROT)-9.3(EOME)]TJ /F6 1 Tf 0 -2.4014 TD [(All)-245(life)-245.6(is)-238.8(linked)-250.9(by)-240.5(a)-241.6(com)-7.6(mon)-244.8(genetic)-249.5(scaf)18.7(fol)-7(d)-239.8(constra)-9.1(ined)-246.6(to)-243.3(4)-239.8(nucleot)-8.7(ides)-242.1(and)-248.8(20)-240.5(amino)]TJ 0 -1.2007 TD [(acids)-409.7(and)-408.1(as)-408.5(such)-410(phenot)-9.1(ypic)-411.6(dif)21.4(ference)-10.7(s)-406(require)-413.9(far)-412(more)-408.7(in)29.9(vestigation)-405.4(than)-411.6(was)]TJ /F3 1 Tf 34.4449 0 TD ()Tj /F6 1 Tf 0.5406 0 TD (rst)Tj -34.9855 -1.2007 TD [(anticipated.)-283(Gen)-8(omics)-274.8(pres)-8(ents)-276.2(only)-273.3(one)-277.2(le)22.4(vel)-268.6(of)-248.2(funct)-10.3(ional)-272.9(inf)-7(ormation.)-281(Both)-272.3(qual)-7.6(itati)17.5(ve)]TJ T* [(and)-413.8(quantitat)-10.1(i)24.9(v)0(e)-407.3(unique)-413.1(le)16.7(vel)10.2(s)-411.7(o)0(f)-401.8(inform)-9.1(ation)-415.1(are)-411.9(also)-412.8(gi)18.5(ven)-402.4(b)-6.5(y)-410.5(the)-410.9(transcr)-11.1(iptome)-413.7(and)]TJ 0 -1.195 TD [(proteome)-308.1(as)-300.4(well)-310.2(as)-300.4(the)-302.7(intera)-9.9(ctome)-303.9(and)-305.7(metabo)-8.7(lome.)]TJ /F11 1 Tf 0 -3.0046 TD [(1.4.1)-1002.8(Tr)-8.2(anscript)-9.2(ome)-333.3(and)-342.5(Proteomi)-11.8(cs)]TJ /F6 1 Tf 0 -1.7982 TD [(T)33.6(rans)-8(cripto)-8.1(me)-496.2(anal)-9.4(ysis)-497.6(in)24.2(vol)12(ves)-494.6(messeng)-9.1(er)-500.4(ribonucl)-9.6(eic)-498(acid)-504.4(\(mRN)22.7(A\),)-497.2(the)-501.9(relayer)-506.8(of)]TJ 0 -1.2007 TD [(informat)-9.5(ion)-471.7(for)-472.9(protei)-8.1(n)-473.1(synthesis.)-479(Se)20.2(veral)-467.3(methods)-8.9(,)-472.7(includi)-9.7(ng)-468.2(serial)-477.7(anal)-9.4(ysis)-474.8(of)-470.1(gene)]TJ T* [(expression)-331.2(\(SA)26.7(GE\))-8(,)-330.4(oligonuc)-7.7(leoti)-8.2(de)-333.4(and)-334.1(com)-7.6(plemen)-8.7(tary)-333.9(deoxyr)-8.3(ibonu)-6.5(cleic)-339(acid)-339.4(\(cDN)25.2(A\))]TJ T* [(microarr)-10.5(ays,)-284.5(and)-282.9(large-scale)-289.7(seque)-8.6(ncing)-287.2(of)-282.3(expressed)-284(tags,)-288(are)-286.7(av)30.8(ailable)-292.1(to)-283.1(measur)-9.1(e)-270(gene)]TJ 0 -1.195 TD [(expression)-496.3(at)-501.1(the)-501.9(mRN)25.4(A)-494.1(l)0(e)16.7(vel)-490.5(globa)-8.3(lly)-497.2(and)-499.1(quant)-8.3(itati)17.5(vely)66.4(.)-495.5(Meas)-9.7(urements)-502.8(of)-498.6(prot)-7.8(ein)]TJ 0 -1.2007 TD 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[(the)-319.8(adv)13(ances)-323.3(that)-329(three)-325.1(model)-324.8(organisms)-320.8(hav)18.7(e)-321.2(a)0(f)17.5(ford)-7(ed)-322(us)-321.4(and)-322.7(ho)21.2(w)-323.4(this)-322.7(inf)-7(ormation)-326.2(has)]TJ T* [(been)-302.5(appl)-7.6(ied)-302.7(to)-300.2(othe)-7.6(r)-298.7(organisms.)]TJ 1.2007 -1.2007 TD [(Life)-430.5(in)-431.1(its)-430.1(most)-431.6(minimal)-437.8(form)-431.6(is)-426.6(still)-431.4(biologi)-7.9(cally)-434(complex.)-425.2(The)-430.7(sma)-8.8(llest)-430.5(bacterial)]TJ -1.2007 -1.195 TD [(genome)-307.5(capab)-9.1(le)-307.7(of)-293.7(independe)-9.2(nt)-305.9(survi)18.7(v)16.3(a)0(l)-302(i)0(s)-307.1(that)-306.3(of)]TJ /F15 1 Tf 20.6339 0 TD [(M.)-305.5(geni)-7.6(talium)]TJ /F6 1 Tf 5.9921 0 TD [(\(517)-306.6(genes)-8.6(\).)-304.7(Intere)-9.2(st)-301.4(in)]TJ -26.6261 -1.2007 TD [(this)-351.2(bact)-9.4(erium)-355.3(has)-358.1(focused)-359.2(on)-354.3(deri)18.9(v)16.3(ation)-352.5(of)-356.3(the)-354(minimal)-358.2(gene)-359.4(set)-355.1(or)-350.6(wha)-8(t)-350.7(i)0(s)-352.6(esse)-9(ntially)]TJ T* [(required)-335(to)-334.3(make)-334.5(a)-332.6(cell)-336.5(ali)18.9(ve.)-322.3(By)-336.3(selecti)14(vel)10.3(y)-336.5(switching)-335(of)19.3(f)-332.8(each)-338.4(gene)-336.7(in)-328.7(turn,)-332.5(Hutchi)-10.1(son)]TJ T* [(et)-404.4(al.)-399.1([50])-405.3(wer)-10(e)-400.9(able)-407.7(to)-402.6(determin)-9.3(e)-400.9(a)0(n)-401.6(esse)-9(ntial)-406.5(require)-9.9(ment)-403.7(of)-401.8(260)]TJ /F3 1 Tf 27.8473 0 TD ()Tj /F6 1 Tf 0.5 0 TD (350)Tj /F15 1 Tf 1.9094 0 TD [(M.)-402.2(geni)-7.6(talium)]TJ /F6 1 Tf -30.2566 -1.2007 TD [(genes,)-486.9(100)-480.3(of)-481.5(which)-484.6(had)-482.1(unkno)13.3(wn)-477.8(functi)-8.1(on.)-479.9(Th)-7(is)-477.8(has)-483.3(since)-483.6(been)-484.6(re)17.5(vised)-487.5(to)-476.6(25)-7.2(0)-478.8(b)0(y)]TJ T* 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[(will)-294.1(also)-287.6(occur)-293.9(with)-291.3(highe)-8.3(r)-287.3(organisms)-286.7(as)-289(the)-291.4(inertia)-298(to)-288.8(propel)-289.9(rese)-9.8(arch)-293.1(forward)-295.8(and)-288.6(unify)]TJ T* [(kno)20.5(wledge)-225.4(is)-216(reached.)-219.7(Th)-7(is)-216(will)-214.4(resu)-8(lt)-211.9(in)-214.8(a)-218.8(holistic)-219.3(under)-7.6(standing)-219.4(that)-215.2(wi)-8.2(ll)-211.9(be)-213.9(b)-6.5(ene)]TJ /F3 1 Tf 32.601 0 TD ()Tj /F6 1 Tf 0.552 0 TD [(cial)-211.4(for)]TJ -33.153 -1.2007 TD [(all)-305.5(biological)-306.7(syst)-8.2(ems.)]TJ /F11 1 Tf 0 -4.0972 TD [(ACK)-8.4(NOWLED)-11.6(GMENTS)]TJ /F6 1 Tf 8.9663 0 0 8.9663 53.8016 306.3117 Tm [(I)-210.8(would)-219.9(like)-210.9(to)-211.7(ackno)16.5(wledge)-217.9(support)-213.1(in)-211.7(part)-215.8(from)-215.5(the)-213.6(Australian)-215.2(Gov)17.1(ernment)-214(Systemic)-214.7(Infrastructure)]TJ 0 -1.2203 TD [(Initiati)16.7(v)13.1(e)-292.8(grant.)]TJ /F11 1 Tf 9.9626 0 0 9.9626 53.8016 254.7212 Tm [(REFER)-9.5(ENCE)-8.9(S)]TJ /F6 1 Tf 8.9663 0 0 8.9663 58.6772 230.57 Tm [(1.)-483(W)74.4(asinger)28.7(,)-319.1(V)123.6(.)-319.1(C.,)-319.9(Cordwell,)-323.7(S.)-317.2(J.,)-322.7(Cerpa-Poljak,)-318.1(A.,)-318.5(Y)92(an,)-320.5(J.)-319.8(X.,)-318.5(Gooley)69(,)-319.1(A)0(.)-315.6(A.,)-318.5(W)30.2(ilkins,)-323.1(M.)-319.3(R.,)]TJ 1.233 -1.2203 TD [(Duncan,)-185.2(M.)-186.5(W)80.8(.)0(,)-182.9(Harris,)-186.9(R.,)-180.8(W)30.2(illiams,)-187.2(K.)-189.1(L.,)-182.2(and)-184.3(Humphery-Smith,)-185.2(I.,)-185(Progress)-188.1(with)-186.5(gene-product)]TJ T* [(mapping)-335.4(of)-330.4(the)-333.8(Mollicutes:)]TJ /F15 1 Tf 11.4761 0 TD [(Mycoplasma)-339.4(genitalium,)-336.1(Electr)39.6(ophor)32.8(esis)]TJ /F6 1 Tf 16.9264 0 TD (1995,)Tj /F17 1 Tf 2.5798 0 TD (16)Tj /F6 1 Tf 1.0053 0 TD [(,)-331.7(1090)]TJ /F3 1 Tf 2.5817 0 TD ()Tj /F6 1 Tf 0.5 0 TD (1094.)Tj -36.3022 -1.4479 TD [(2.)-483(W)74.4(asinger)28.7(,)-521.4(V)123.6(.)-521.4(C.,)-522.2(Pollack,)-523.2(J.)-522.1(D.,)-520.8(and)-525.8(Humphery-Smith,)-520.3(I.,)-520.1(The)-525.6(proteome)-523.3(of)]TJ /F15 1 Tf 34.3271 0 TD (Mycoplasma)Tj -33.0941 -1.2203 TD (genitalium)Tj /F6 1 Tf 4.2933 0 TD [(;)-332.3(CHAPS)-334.9(soluble)-337.1(component,)]TJ /F15 1 Tf 12.4245 0 TD [(Eur)101.6(.)-331.7(J)23.4(.)-338(Bioc)14.7(hem.)]TJ /F6 1 Tf 7.069 0 TD (2000,)Tj /F17 1 Tf 2.5861 0 TD (267)Tj /F6 1 Tf 1.4985 0 TD [(,)-331.7(1571)]TJ /F3 1 Tf 2.5817 0 TD ()Tj /F6 1 Tf 0.5 0 TD (1582.)Tj -32.186 -1.4479 TD [(3.)-483(Ghaemmaghami,)-290.3(S.,)-282.2(Huh,)-283(W)61.8(-K.,)-289(Bo)21.5(wer)31.1(,)-287.4(K.,)-280.6(Ho)16.6(wson,)-283.7(R.,)-288.3(Belle,)-283.7(A.,)-286.9(Dephoure,)-288(N.,)-280.6(O)]TJ /F3 1 Tf 35.513 0 TD ()Tj /F6 1 Tf 0.333 0 TD [(Shea,)-287.6(E.,)]TJ -34.613 -1.2203 TD [(and)-329.8(W)74.4(eissman,)-330.5(J.,)-329(Global)-327(analysis)-327.5(of)-330.4(protein)-325.8(expressio)9.5(n)-328.3(i)0(n)-319.2(yeast,)]TJ /F15 1 Tf 26.9419 0 TD [(Nat.)-326.4(Biotechn)10.1(ol.)]TJ /F6 1 Tf 6.9426 0 TD (2003,)Tj /F17 1 Tf 2.5798 0 TD (425)Tj /F6 1 Tf 1.4985 0 TD (,)Tj -37.9628 -1.2203 TD (737)Tj /F3 1 Tf 1.5 0 TD ()Tj /F6 1 Tf 0.5 0 TD (741.)Tj -3.2329 -1.4479 TD [(4.)-483(Adami,)-260.4(C.,)-250.4(Ofria,)-262(C.,)-250.4(and)-260.2(Collier)32.2(,)-255.8(T)70.2(.)-255.8(C.,)-250.4(Evolution)-247.8(of)-254.5(biological)-256.4(complexity)]TJ /F15 1 Tf 31.3869 0 TD 0.2558 Tc [(,P)255.8(N)277.5(A)255.8(S)]TJ /F6 1 Tf 3.1362 0 TD 0 Tc (2000,)Tj /F17 1 Tf 2.5039 0 TD (97)Tj /F6 1 Tf 0.999 0 TD (\(9\),)Tj -36.793 -1.2203 TD (4463)Tj /F3 1 Tf 2 0 TD ()Tj /F6 1 Tf 0.5 0 TD (4468.)Tj -3.7329 -1.4416 TD [(5.)-483(Southan,)-377.6(C.,)-383.1(Has)-378.5(the)-365.4(yo-yo)-379.6(stopped?)-379.2(An)-381.7(assessment)-381.5(of)-381(human)-376.6(protein-coding)-382.1(gene)-376(number)26(,)]TJ /F15 1 Tf 1.233 -1.2266 TD [(Pr)37.9(oteomics)]TJ /F6 1 Tf 4.856 0 TD (2004,)Tj /F17 1 Tf 2.5797 0 TD (4)Tj /F6 1 Tf 0.4995 0 TD [(\(6\),)-335.5(1712)]TJ /F3 1 Tf 3.7514 0 TD ()Tj /F6 1 Tf 0.5 0 TD (1726.)Tj -13.4196 -1.4416 TD [(6.)-483(Jaenisch,)-221.4(R.,)-218.7(and)-222.3(Bird,)-221(A.,)-217.3(Epigenetic)-223(regulation)-217(of)-216.6(gene)-217.9(expression:)-214.9(Ho)23(w)-224.1(the)-207.3(genome)-220.5(integrates)]TJ 1.233 -1.2203 TD [(intrinsic)-334.1(and)-336.1(en)30.2(vironmental)-333.9(signals,)]TJ /F15 1 Tf 14.8715 0 TD [(Nat.)-332.7(Genet.)]TJ /F6 1 Tf 5.0141 0 TD (2003,)Tj /F17 1 Tf 2.5797 0 TD (33)Tj /F6 1 Tf 0.999 0 TD [(,)-331.7(s245)]TJ /F3 1 Tf 2.4667 0 TD ()Tj /F6 1 Tf 0.5 0 TD (254.)Tj /F12 1 Tf 6.9738 0 0 6.9738 337.6062 669.7699 Tm [(REFER)-16(ENCES)]TJ /F11 1 Tf 8.9663 0 0 8.9663 402.4629 669.7699 Tm (11)Tj ET endstream endobj 38 0 obj > endobj 39 0 obj > /ExtGState > >> endobj 40 0 obj > stream BT /F6 1 Tf 8.9663 0 0 8.9663 96.548 640.2896 Tm 0 g /GS2 gs 0 Tc 0 Tw [(7.)-483(Strohman,)-237.9(R.,)-237.7(Epigenesis:)-241.4(The)-241.1(missing)-238.2(beat)-234.5(in)-243.3(biotechnology?)]TJ /F15 1 Tf 26.3918 0 TD [(Biotechn)10.1(ology)-238(\(NY\))]TJ /F6 1 Tf 8.1502 0 TD (1994,)Tj /F17 1 Tf 2.4849 0 TD (12)Tj /F6 1 Tf 0.999 0 TD (\(2\),)Tj -36.793 -1.2203 TD (156)Tj /F3 1 Tf 1.5 0 TD ()Tj /F6 1 Tf 0.5 0 TD (164.)Tj -3.2329 -1.448 TD [(8.)-483(K)22.5(ellner)25.4(,)-211.6(R.,)-212.4(Proteomics.)-212.9(Concepts)-213.2(and)-209.6(perspecti)16.9(ves,)]TJ /F15 1 Tf 21.9911 0 TD [(F)57.6(r)24.6(enius)-207.5(J)17(.)-211.6(Anal.)-213.5(Chem.)]TJ /F6 1 Tf 9.282 0 TD (2000,)Tj /F17 1 Tf 2.4596 0 TD (366)Tj /F6 1 Tf 1.4985 0 TD [(,)-211.6(517)]TJ /F3 1 Tf 1.9615 0 TD ()Tj /F6 1 Tf 0.5 0 TD (524.)Tj -37.6928 -1.4416 TD [(9.)-483(Harrison,)-337.7(P)103.1(.)-338(M.,)-334.9(Kuma)11.6(r)29.5(,)-338(A.,)-337.5(Lang,)-338.3(N.,)-337.5(Sn)15(yder)28.5(,)-338(M.,)-334.9(and)-336.1(Gerstein,)-341.5(M.,)-334.9(A)-337.9(question)-336.6(of)-336.8(size:)-340.4(The)]TJ 1.233 -1.2203 TD [(eukaryotic)-196.4(proteome)-194.5(and)-190.7(the)-194.7(problems)-193.3(in)-192.7(de)]TJ /F3 1 Tf 17.317 0 TD ()Tj /F6 1 Tf 0.5389 0 TD [(ning)-191.8(it,)]TJ /F15 1 Tf 2.9781 0 TD [(Nucleic)-200(Acids)-188.4(Res.)]TJ /F6 1 Tf 7.5749 0 TD (2002,)Tj /F17 1 Tf 2.4406 0 TD (30)Tj /F6 1 Tf 1.0053 0 TD [(\(5\),)-190(1083)]TJ /F3 1 Tf 3.606 0 TD ()Tj /F6 1 Tf 0.5 0 TD (1090.)Tj -37.6933 -1.448 TD [(10.)-482.5(Gra)12.1(vele)18.4(y)57.4(,)-224.2(B.)-222.1(R.,)-225.1(Alternati)15.5(v)13.1(e)-229.6(splicing:)-224(Increasing)-227.8(di)22.2(versity)-219.5(in)-224.3(the)-226.3(proteomic)-223.3(world,)]TJ /F15 1 Tf 34.384 0 TD [(T)52.5(r)30.9(ends)-229.3(Genet)]TJ /F6 1 Tf 5.3112 0 TD (.)Tj -37.9628 -1.2203 TD (2001,)Tj /F17 1 Tf 2.5797 0 TD (17)Tj /F6 1 Tf 1.0053 0 TD [(\(2\),)-329.1(100)]TJ /F3 1 Tf 3.2451 0 TD ()Tj /F6 1 Tf 0.5 0 TD (107.)Tj -9.0627 -1.4479 TD [(11.)-482.5(Huang,)-417.2(S.,)-414.9(Back)-418.6(to)-414(the)-416(biology)-415.7(in)-420.4(systems)-414.8(biology:)-419.2(What)-417.4(can)-414.4(we)-415.7(learn)-420(from)-417.8(biomolecular)]TJ 1.7325 -1.2203 TD (networks?)Tj /F15 1 Tf 4.445 0 TD [(Brief)-337.8(Funct.)-335.6(Genomic)-334.6(Pr)44.2(oteomic)]TJ /F6 1 Tf 13.6891 0 TD (2004,)Tj /F17 1 Tf 2.5797 0 TD (2)Tj /F6 1 Tf 0.4995 0 TD [(\(4\),)-335.5(279)]TJ /F3 1 Tf 3.2514 0 TD ()Tj /F6 1 Tf 0.5 0 TD (297.)Tj -26.6973 -1.4416 TD [(12.)-482.5(Zhu,)-184.7(H.,)-185.7(Huang,)-183.3(S.,)-181(and)-184.3(Dhar)25.2(,)-180(P)103.1(.,)-182.9(The)-184.1(next)-175.2(step)-189.1(in)-180.1(systems)-187.2(biology:)-185.2(Simulating)-186.5(the)-182(temporospatial)]TJ 1.7325 -1.2266 TD [(dynamics)-332.2(of)-336.8(molecular)-333.2(network,)]TJ /F15 1 Tf 13.5563 0 TD (Bioessays)Tj /F6 1 Tf 4.2806 0 TD (2004,)Tj /F17 1 Tf 2.5861 0 TD (26)Tj /F6 1 Tf 0.999 0 TD [(\(1\),)-335.5(68)]TJ /F3 1 Tf 2.7514 0 TD ()Tj /F6 1 Tf 0.5 0 TD (72.)Tj -26.4059 -1.4416 TD [(13.)-482.5(Date,)-209.2(S.)-203.4(V)123.6(.)0(,)-201.8(and)-209.6(Marcotte,)-207.3(E.)-204.6(M.,)-202.1(Discov)17.3(ery)-205.9(of)-204(uncharacterized)-212.6(cellular)-207.7(systems)-206.2(by)-207.7(genome-wide)]TJ 1.7325 -1.2203 TD [(analysis)-333.9(of)-311.5(functional)-337.1(linkages,)]TJ /F15 1 Tf 13.0378 0 TD [(Nat.)-332.7(Biotechnol)]TJ /F6 1 Tf 6.3735 0 TD [(.)-331.7(2003,)]TJ /F17 1 Tf 3.1678 0 TD (21)Tj /F6 1 Tf 0.999 0 TD [(\(9\),)-335.5(1055)]TJ /F3 1 Tf 3.7514 0 TD ()Tj /F6 1 Tf 0.5 0 TD (1062.)Tj -29.562 -1.4479 TD [(14.)-482.5(Pelleg)10.4(rini,)-296.2(M.,)-296.9(Marcotte,)-302.2(E.)-293.1(M.,)-296.9(Thompson,)-294.5(M.)-300.3(J.,)-297.4(Eisenber)10.4(g,)-293.3(D.,)-299.5(and)-298.1(Y)92(eates,)-297.5(T)76.5(.)-300.1(O.,)-293.2(Assigning)]TJ 1.7325 -1.2203 TD [(protein)-357.4(functions)-357.7(by)-359.4(comparati)20.8(ve)-336.6(genome)-359.6(analysis:)-362.7(Protein)-356(phylogenetic)-361.3(pro)]TJ /F3 1 Tf 31.4553 0 TD ()Tj /F6 1 Tf 0.5386 0 TD (les,)Tj /F15 1 Tf 1.7262 0 TD [(Pr)44.2(oc.)-358.5(Natl.)]TJ -33.7201 -1.2203 TD [(Acad.)-332(Sci.)-336.7(USA)]TJ /F6 1 Tf 6.6201 0 TD (1999,)Tj /F17 1 Tf 2.5861 0 TD (96)Tj /F6 1 Tf 0.999 0 TD [(\(8\),)-335.5(4285)]TJ /F3 1 Tf 3.7514 0 TD ()Tj /F6 1 Tf 0.5 0 TD (4288.)Tj -16.1891 -1.4479 TD [(15.)-482.5(Marcotte,)-239(E.)-236.2(M.,)-233.7(Pelleg)10.4(rini,)-232.9(M.,)-240(Thompson,)-231.2(M.)-237.1(J.,)-234.2(Y)92(eates,)-234.3(T)70.2(.)-236.9(O.,)-230(and)-234.9(Eisenberg,)-232.3(D.,)-230(A)-236.8(combined)]TJ 1.7325 -1.2203 TD [(algorithm)-332.4(for)-326.2(genome-wide)-337.9(prediction)-330.8(of)-336.8(protein)-332.1(function,)]TJ /F15 1 Tf 24.1915 0 TD [(Natur)30.4(e)]TJ /F6 1 Tf 3.0856 0 TD (1999,)Tj /F17 1 Tf 2.5797 0 TD (402)Tj /F6 1 Tf 1.5049 0 TD [(\(6757\),)-327.7(83)]TJ /F3 1 Tf 4.2436 0 TD ()Tj /F6 1 Tf 0.5 0 TD (86.)Tj -37.8377 -1.4479 TD [(16.)-482.5(Enright,)-250.3(A.)-252.3(J.,)-253.1(Iliopoulos,)-254.2(I.,)-254.6(K)22.5(yrpides,)-250(N.)-258.7(C.,)-250.3(and)-253.9(Ouzounis,)-250.3(C.)-253.7(A.,)-255.3(Protein)-248.5(interaction)-254.6(maps)-258.1(for)]TJ 1.7325 -1.2203 TD [(complete)-324.8(genomes)-335(based)-338.7(on)-327.8(gene)-338(fusion)-333.7(e)23.4(vents,)]TJ /F15 1 Tf 20.0247 0 TD [(Natur)30.4(e)]TJ /F6 1 Tf 3.0856 0 TD (1999,)Tj /F17 1 Tf 2.5798 0 TD (402)Tj /F6 1 Tf 1.5048 0 TD [(\(6757\),)-334(86)]TJ /F3 1 Tf 4.25 0 TD ()Tj /F6 1 Tf 0.5 0 TD (90.)Tj -33.6773 -1.4416 TD [(17.)-482.5(Dandekar)28.6(,)-281.1(T)76.6(.,)-284(Snel,)-277.9(B.,)-282(Huynen,)-277.6(M.,)-284.3(and)-279.2(Bork,)-280.2(P)103.1(.)0(,)-277.7(Conserv)17.7(ation)-279.9(of)-279.8(gene)-281.1(order:)-280.6(A)]TJ /F3 1 Tf 34.6116 0 TD ()Tj /F6 1 Tf 0.552 0 TD [(nger)11.4(print)-280.1(of)]TJ -33.4311 -1.2266 TD [(proteins)-332.9(that)-337.3(physically)-335.7(interact,)]TJ /F15 1 Tf 13.4678 0 TD [(T)52.5(r)30.9(ends)-330.5(Biochem.)-327.7(Sci.)]TJ /F6 1 Tf 8.9153 0 TD (1998,)Tj /F17 1 Tf 2.5798 0 TD (23)Tj /F6 1 Tf 0.999 0 TD [(\(9\),)-335.5(324)]TJ /F3 1 Tf 3.2514 0 TD ()Tj /F6 1 Tf 0.5 0 TD (328.)Tj -31.4458 -1.4416 TD [(18.)-482.5(Corthals,)-372.1(G.)-372.5(L.,)-371.9(W)74.4(asinger)28.7(,)-369.6(V)123.6(.)-376(C.,)-370.5(Hochstrasser)-371.6(D.)-372.5(F)71.5(.)0(,)-372.6(and)-367.7(Sanchez,)-374.5(J-C.,)-373.3(The)-373.8(dynamic)-375.7(range)]TJ 1.7325 -1.2203 TD [(of)-678.2(protein)-686.2(expres)13.2(sion:)-683.4(A)-685.7(challenge)-683.6(for)-680.3(proteomic)-684.9(research,)]TJ /F15 1 Tf 27.0747 0 TD [(Electr)33.3(ophor)32.8(esis)]TJ /F6 1 Tf 6.9552 0 TD (2000,)Tj /F17 1 Tf 2.9275 0 TD (21)Tj /F6 1 Tf 0.999 0 TD (,)Tj -37.9564 -1.2266 TD (1104)Tj /F3 1 Tf 2 0 TD ()Tj /F6 1 Tf 0.5 0 TD (1115.)Tj -4.2324 -1.4416 TD [(19.)-482.5(Oda,)-272.8(Y)123.6(.)0(,)-271.4(Nagasu,)-274.9(T)70.2(.)0(,)-271.4(and)-272.9(Chait,)-268.6(B.)-272.7(T)70.2(.)0(,)-271.4(Enrichment)-273.2(analysis)-276.9(of)-273.5(phosphorylated)-275.5(proteins)-269.6(as)-274.5(a)-273.8(tool)]TJ 1.7325 -1.2266 TD [(for)-332.5(probing)-332(the)-333.8(phosphoproteome,)]TJ /F15 1 Tf 14.2708 0 TD [(Nat.)-332.7(Biotechn)10.1(ol.)]TJ /F6 1 Tf 6.9552 0 TD (2001,)Tj /F17 1 Tf 2.5797 0 TD (19)Tj /F6 1 Tf 0.999 0 TD [(,)-338(379)]TJ /F3 1 Tf 2.088 0 TD ()Tj /F6 1 Tf 0.5 0 TD (382.)Tj -29.1252 -1.4416 TD [(20.)-482.5(Krishna,)-303.9(R.)-304.3(G.,)-299.5(and)-304.5(W)74.4(old,)-302.7(F)71.5(.)0(,)-303(Post-translational)-307.1(modi)]TJ /F3 1 Tf 23.3133 0 TD ()Tj /F6 1 Tf 0.5368 0 TD [(cation)-307.2(of)-298.8(proteins,)]TJ /F15 1 Tf 7.676 0 TD [(Adv)68.8(.)-300.1(Enzymol.)-307.5(Relat.)]TJ -29.7936 -1.2203 TD [(Ar)31.6(eas)-337.3(Mol.)-330.1(Biol)]TJ /F6 1 Tf 6.5063 0 TD [(.)-338(1993,)]TJ /F17 1 Tf 3.1678 0 TD (67)Tj /F6 1 Tf 0.999 0 TD [(,)-331.7(265)]TJ /F3 1 Tf 2.0817 0 TD ()Tj /F6 1 Tf 0.5 0 TD (298.)Tj -14.9872 -1.4479 TD [(21.)-482.5(James,)-333.7(P)103.1(.)0(,)-334.6(Mass)-332.4(spectrometry)-335.6(and)-329.8(the)-333.8(proteome,)-336.5(in)-331.8(P)103.1(.)-331.7(James)-337.1(\(Ed.\),)]TJ /F15 1 Tf 29.3004 0 TD [(Pr)37.9(oteome)-331.7(Resear)27.5(ch:)-319.7(Mass)]TJ -27.5679 -1.2203 TD [(Spectr)43.4(ometry)]TJ /F6 1 Tf 5.2354 0 TD [(,)-338(Springer)31.6(,)-331.7(2001,)-336.1(p.)-331.2(6.)]TJ -6.9678 -1.4416 TD [(22.)-482.5(W)74.4(asinger)28.7(,)-224.2(V)123.6(.)-224.2(C.,)-225.1(Bjellqvist,)-228.9(B.,)-225.1(and)-228.6(Humphery-Smith,)-229.5(I.,)-222.9(Proteomic)]TJ /F3 1 Tf 28.7439 0 TD -0.0738 Tc ()Tj /F6 1 Tf 0.5922 0 TD 0 Tc (contigs)Tj /F3 1 Tf 2.8939 0 TD -0.0697 Tc ()Tj /F6 1 Tf 0.8197 0 TD 0 Tc (of)Tj /F15 1 Tf 1.0622 0 TD [(Ochr)51.9(obactrum)]TJ -32.3796 -1.2267 TD [(anthr)41.5(opi)]TJ /F6 1 Tf 3.408 0 TD [(,)-331.7(application)-334.2(of)-336.7(ext)14(ensi)19.6(ve)-323.9(pH)-337.4(gradients,)]TJ /F15 1 Tf 16.4396 0 TD [(Electr)33.3(ophor)32.8(esis)]TJ /F6 1 Tf 6.6074 0 TD (1997,)Tj /F17 1 Tf 2.5797 0 TD (18)Tj /F6 1 Tf 0.999 0 TD [(,)-338(1373)]TJ /F3 1 Tf 2.588 0 TD ()Tj /F6 1 Tf 0.5 0 TD (1383.)Tj -34.8543 -1.4416 TD [(23.)-482.5(Cordwell,)-273.1(S.)-266.6(J.,)-265.8(Basseal,)-277.2(D.)-265(J.,)-272.1(Bjellqvist,)-266.8(B.,)-269.3(Shaw)67.2(,)-268.5(D)0(.)-265(C.,)-269.3(and)-272.9(Humphery-Smith,)-267.4(I.,)-267.2(Character-)]TJ 1.7325 -1.2266 TD [(isation)-328.4(of)-324.1(basic)-323.8(proteins)-326.5(from)]TJ /F15 1 Tf 12.3676 0 TD [(Spir)41(oplasma)-327.6(melliferum)]TJ /F6 1 Tf 10.0028 0 TD [(using)-325.3(nov)20.4(el)-327.9(immobilised)-324.9(pH)-324.8(gradients,)]TJ /F15 1 Tf -22.3705 -1.2203 TD [(Electr)39.6(ophor)32.8(esis)]TJ /F6 1 Tf 6.6011 0 TD (1997,)Tj /F17 1 Tf 2.5861 0 TD (18)Tj /F6 1 Tf 0.999 0 TD [(\(8\),)-335.5(1393)]TJ /F3 1 Tf 3.7514 0 TD ()Tj /F6 1 Tf 0.5 0 TD (1398.)Tj -16.1701 -1.4416 TD [(24.)-482.5(Urquhart,)-222.7(B.)-215.8(L.,)-220.2(Cordwell,)-222.5(S.)-216(J,)-218.6(and)-222.3(Humphery-Smith,)-216.8(I.,)-222.9(Comparison)-216(of)-222.9(predicted)-222.2(and)-215.9(observed)]TJ 1.7325 -1.2266 TD [(properties)-254.7(of)-260.9(proteins)-257(encoded)-256.8(in)-256(the)-245.3(genome)-258.4(of)]TJ /F15 1 Tf 19.4682 0 TD [(Mycobacterium)-258.3(tuber)26.4(culosis)]TJ /F6 1 Tf 11.6658 0 TD [(H37Rv)63.9(,)]TJ /F15 1 Tf 3.3258 0 TD (Biochem.)Tj -34.4599 -1.2203 TD [(Biophys.)-335.8(Res.)-333.7(Commun.)]TJ /F6 1 Tf 10.0281 0 TD (1998,)Tj /F17 1 Tf 2.5861 0 TD (253)Tj /F6 1 Tf 1.4985 0 TD [(\(1\),)-335.5(70)]TJ /F3 1 Tf 2.7514 0 TD ()Tj /F6 1 Tf 0.5 0 TD (79.)Tj -19.0966 -1.4416 TD [(25.)-482.5(Schaf)21.7(fer)25.4(,)-243.2(S.,)-244.2(W)68.1(eil,)-245.9(B.,)-244(Nguyen,)-246(V)123.6(.)-243.2(D.,)-248.9(Dongmann,)-242.3(G.,)-248.9(Gunther)29(,)-243.2(K.,)-248.9(Nickolaus,)-243.6(M.,)-246.3(Hermann,)-247.8(T)70.2(.)0(,)]TJ 1.7325 -1.2266 TD [(and)-494.2(Bott,)-494.3(M.,)-492.9(A)-496(high-resolution)-491.9(reference)-502.4(map)-491.4(for)-490.6(cytoplasmic)-486.6(and)-494.2(membrane-associated)]TJ 0 -1.2203 TD [(proteins)-332.9(of)]TJ /F15 1 Tf 4.7295 0 TD [(Corynebacterium)-337(glutamicum)]TJ /F6 1 Tf 12.0704 0 TD (,)Tj /F15 1 Tf 0.5817 0 TD [(Electr)39.6(ophor)32.8(esis)]TJ /F6 1 Tf 6.6011 0 TD (2001,)Tj /F17 1 Tf 2.5861 0 TD (22)Tj /F6 1 Tf 0.999 0 TD [(\(20\),)-335(4404)]TJ /F3 1 Tf 4.2509 0 TD ()Tj /F6 1 Tf 0.5 0 TD (4422.)Tj -34.0513 -1.4416 TD [(26.)-482.5(Len,)-206(A.)-208.1(C.,)-206.1(Cordwell,)-209.8(S.)-203.4(J.,)-208.9(Harty)59.6(,)-205.2(D)0(.)-208.1(W)87.1(.,)-208.2(and)-209.6(Jacques,)-205.2(N.)-208.1(A.,)-211(Cellular)-203.7(and)-209.6(extr)11.9(acellular)-216(proteome)]TJ 1.7325 -1.2266 TD [(analysis)-333.9(of)]TJ /F15 1 Tf 4.7295 0 TD [(Str)34.2(eptococcus)-338.8(mutans)]TJ /F6 1 Tf 9.1429 0 TD [(gro)24.1(wn)-337.4(in)-331.8(a)-337(chemostat,)]TJ /F15 1 Tf 9.4148 0 TD [(Pr)44.2(oteomics)]TJ /F6 1 Tf 4.856 0 TD (2003,)Tj /F17 1 Tf 2.5798 0 TD (3)Tj /F6 1 Tf 0.4995 0 TD [(\(5\),)-335.5(627)]TJ /F3 1 Tf 3.2514 0 TD ()Tj /F6 1 Tf 0.5 0 TD (646.)Tj -36.7064 -1.4416 TD [(27.)-482.5(Mdluli,)-215.1(K.,)-217.3(Slayden,)-222(R.)-215.8(A.,)-217.3(Zhu,)-222.6(Y)123.6(.)0(,)-214.5(Ramaswamy)56.7(,)-217.9(S.,)-212.6(Pan,)-211.1(X.,)-217.3(Mead,)-221.5(D.,)-217.3(Crane,)-215(D.)-220.7(D.,)-217.3(Musser)26.4(,)-217.9(J)0(.)]TJ 1.7325 -1.2203 TD [(M.,)-467.6(and)-462.5(Barry)59.6(,)-464.5(C)0(.)-468.7(E)0(.)-463.8(3rd.,)-468.6(Inhibition)-469.1(of)-463.2(a)]TJ /F15 1 Tf 18.3491 0 TD [(Mycobacterium)-467(tuber)26.4(culosis)]TJ /F6 1 Tf 12.0831 0 TD [(beta-ketoac)7.9(yl)-471(A)35.1(C)0(P)]TJ -30.4322 -1.2266 TD [(synthase)-336.2(by)-334.1(isoniazid,)]TJ /F15 1 Tf 9.32 0 TD (Science)Tj /F6 1 Tf 3.4081 0 TD (1998,)Tj /F17 1 Tf 2.5797 0 TD (280)Tj /F6 1 Tf 1.4985 0 TD [(\(5369\),)-334(1607)]TJ /F3 1 Tf 5.2499 0 TD ()Tj /F6 1 Tf 0.5 0 TD (1610.)Tj /F11 1 Tf -24.333 63.9563 TD (12)Tj /F12 1 Tf 6.9738 0 0 6.9738 118.885 669.7699 Tm [(HOLISTIC)-404.8(BIOL)44.4(OGY)-340.9(OF)-401.6(MICROORGANISMS)]TJ ET endstream endobj 41 0 obj > endobj 42 0 obj > /ExtGState > >> endobj 43 0 obj > stream BT /F6 1 Tf 8.9663 0 0 8.9663 54.1984 640.2896 Tm 0 g /GS2 gs 0 Tc 0 Tw [(28.)-482.5(W)30.2(ilson,)-287.9(M.,)-290.6(DeRisi,)-291.6(J.,)-291.1(Kristensen,)-291.1(H.)-290.3(H.,)-286.9(Imboden,)-292.6(P)109.4(.)0(,)-290.4(Rane,)-295.1(S.,)-288.5(Bro)25.7(wn,)-289.8(P)103.1(.)-287.4(O.,)-293.2(and)-285.5(Schoolnik,)]TJ 1.7325 -1.2203 TD [(G.)-359.8(K.,)-362.7(Exploring)-360.2(drug-induced)-362.4(alterations)-363.2(in)-363.5(gene)-357(expression)-356.8(in)]TJ /F15 1 Tf 26.6953 0 TD [(Mycobacterium)-365.8(tuber)32.7(culosis)]TJ /F6 1 Tf -26.6953 -1.2203 TD [(by)-334.1(microarray)-333.9(hybridization,)]TJ /F15 1 Tf 12.0072 0 TD [(Pr)37.9(oc.)-333.2(Natl.)-336.2(Acad.)-332(Sci.)-336.7(USA)]TJ /F6 1 Tf 11.0967 0 TD [(,)-331.7(1999,)]TJ /F17 1 Tf 3.1615 0 TD (96)Tj /F6 1 Tf 0.999 0 TD [(\(22\),)-335(12833)]TJ /F3 1 Tf 4.7509 0 TD ()Tj /F6 1 Tf 0.5 0 TD (12838.)Tj -34.2478 -1.4479 TD [(29.)-482.5(Cov)22(ert,)-377.2(B.)-373.9(A.,)-375.4(Spencer)26.6(,)-376(J)0(.)-376.7(S.,)-370.7(Orme,)-379.6(I.)-371.8(M.,)-379.1(and)-374(Belisle,)-376.4(J.)-376.7(T)70.2(.)0(,)-372.6(The)-373.8(application)-378.4(of)-374.7(proteomics)]TJ 1.7325 -1.2203 TD [(in)-237(de)]TJ /F3 1 Tf 1.965 0 TD ()Tj /F6 1 Tf 0.552 0 TD [(ning)-229.3(the)-238.9(T)-233.3(cell)-238.6(antigens)-237.8(of)]TJ /F15 1 Tf 10.6726 0 TD [(Mycobacterium)-239.4(tuber)32.7(culosis,)-240(Pr)37.9(oteomics)]TJ /F6 1 Tf 16.6356 0 TD (2001,)Tj /F17 1 Tf 2.4849 0 TD (1)Tj /F6 1 Tf 0.4995 0 TD [(\(4\),)-234.3(574)]TJ /F3 1 Tf 3.1502 0 TD ()Tj /F6 1 Tf 0.5 0 TD (586.)Tj -38.1923 -1.4479 TD [(30.)-482.5(Gulle,)-260.9(H.,)-255.3(Fray)61.6(,)-255.8(L)0(.)-255.2(M.,)-259(Gormle)12.3(y)63.7(,)-255.8(E.)-261.5(P)109.4(.)0(,)-258.8(Murray)57.8(,)-255.8(A.,)-255.3(and)-253.9(Moriarty)57(,)-255.8(K)0(.)-252.3(M.,)-259(Responses)-255.4(of)-260.9(bo)13.6(vine)-257.4(T)]TJ 1.7325 -1.2203 TD [(cells)-447.9(to)-445.7(fractionated)-444.8(lysate)-447.4(and)-443.6(culture)]TJ /F3 1 Tf 16.6735 0 TD ()Tj /F6 1 Tf 0.552 0 TD [(ltrate)-438.3(proteins)-446.7(of)]TJ /F15 1 Tf 7.4591 0 TD [(Mycobacterium)-448(bovis)]TJ /F6 1 Tf 9.2884 0 TD (BCG,)Tj /F15 1 Tf 2.7505 0 TD [(V)108.2(et.)]TJ -36.7235 -1.2203 TD [(Immunol.)-335.3(Immunopathol.)]TJ /F6 1 Tf 10.5529 0 TD (1995,)Tj /F17 1 Tf 2.5797 0 TD (48)Tj /F6 1 Tf 0.999 0 TD (\(1)Tj /F3 1 Tf 0.833 0 TD ()Tj /F6 1 Tf 0.5 0 TD [(2\),)-334.5(183)]TJ /F3 1 Tf 2.9175 0 TD ()Tj /F6 1 Tf 0.5 0 TD (190.)Tj -20.6146 -1.4479 TD [(31.)-482.5(Jungblut,)-299.1(P)109.4(.)-300.1(R.,)-294.6(Schaible,)-297.5(U.)-296.6(E.,)-296(Mollenkopf,)-296.4(H.)-296.6(J.,)-291.1(Zimny-Arndt,)-289.4(U.,)-293.2(Raupach,)-302.4(B.,)-294.6(Matto)22.9(w)60.4(,)-293.8(J.,)]TJ 1.7325 -1.2203 TD [(Halada,)-375(P)103.1(.)0(,)-372.6(Lamer)29.6(,)-376(S.,)-370.7(Hagens,)-376.1(K.,)-375.4(and)-374(Kaufmann,)-373.8(S.)-374.1(H.,)-375.4(Comparati)18.5(v)13.1(e)-375(proteome)-377.9(analysis)-371.8(of)]TJ /F15 1 Tf T* [(Mycobacterium)-599.8(tuber)26.4(culosis)]TJ /F6 1 Tf 12.3486 0 TD (and)Tj /F15 1 Tf 2.0486 0 TD [(Mycobacterium)-599.8(bovis)]TJ /F6 1 Tf 9.5982 0 TD [(BCG)-599.3(strains:)-597.3(T)70.2(o)25.8(wards)-601.5(functional)]TJ -23.9954 -1.2266 TD [(genomics)-338.5(of)-330.4(microbial)-334.8(pathogens,)]TJ /F15 1 Tf 14.176 0 TD [(Mol.)-330.1(Micr)36.5(obiol)]TJ /F6 1 Tf 6.1648 0 TD [(.)-331.7(1999,)]TJ /F17 1 Tf 3.1678 0 TD (33)Tj /F6 1 Tf 0.999 0 TD [(\(6\),)-335.5(1103)]TJ /F3 1 Tf 3.7514 0 TD ()Tj /F6 1 Tf 0.5 0 TD (1117.)Tj -30.4915 -1.4416 TD [(32.)-482.5(Botstein,)-430.4(D.,)-426(Chervitz)-427.3(S.)-431(A.,)-426(and)-430.9(Cherry)-426.8(J.)-427.3(M.,)-423.4(Y)92(east)-431.7(as)-426.3(a)-425.6(model)-431.2(organi)12.8(sm,)]TJ /F15 1 Tf 34.1943 0 TD (Science)Tj /F6 1 Tf 3.4966 0 TD (1997,)Tj /F17 1 Tf -35.9584 -1.2203 TD (277)Tj /F6 1 Tf 1.4985 0 TD [(\(5330\),)-334(1259)]TJ /F3 1 Tf 5.2499 0 TD ()Tj /F6 1 Tf 0.5 0 TD (1260.)Tj -8.9809 -1.4479 TD [(33.)-482.5(Anderson,)-267.8(N.)-265(L.,)-264.4(Polanski,)-268.5(M.,)-265.3(Pieper)30.8(,)-268.5(R.,)-263(Gatlin,)-270.7(T)76.6(.)0(,)-265.1(T)32.3(irumalai,)-268.7(R.)-266.4(S.,)-263.2(Conrads,)-269.7(T)70.2(.)-262.2(P)103.1(.)0(,)-265.1(V)104.7(eenstra,)]TJ 1.7325 -1.2203 TD [(T)70.2(.)-274.8(D.,)-280.5(Adkins,)-274.1(J.)-275.5(N.,)-280.5(Pounds,)-278(J.)-275.5(G.,)-274.2(Fagan,)-269.5(R.,)-275.6(and)-279.2(Lobley)72.5(,)-281.1(A.,)-274.2(The)-279(human)-275.4(plasma)-282.6(proteome:)-280.2(A)]TJ T* [(nonredundant)-391.4(list)-390.7(de)23.8(veloped)-384.9(by)-384.7(combination)-394.5(of)-368.4(four)-389(separate)-393(sources,)]TJ /F15 1 Tf 29.3699 0 TD [(Mol.)-393.3(Cell)-386.3(Pr)37.9(oteomics)]TJ /F6 1 Tf -29.3699 -1.2266 TD (2004,)Tj /F17 1 Tf 2.5861 0 TD (3)Tj /F6 1 Tf 0.4995 0 TD [(\(4\),)-329.1(311)]TJ /F3 1 Tf 3.2451 0 TD ()Tj /F6 1 Tf 0.5 0 TD (326.)Tj -8.5631 -1.4416 TD [(34.)-482.5(V)47.8(itali,)-360.4(B.,)-370.5(W)74.4(asinger)28.7(,)-363.3(V)123.6(.,)-366.2(Brigidi,)-360.4(P)103.1(.)0(,)-366.2(and)-367.7(Guilhaus,)-361.8(M.,)-366.5(A)-363.2(proteomic)-368.8(vie)20.3(w)-363.2(o)0(f)]TJ /F15 1 Tf 33.4988 0 TD (Bi)Tj /F4 1 Tf 0.895 0 TD ()Tj /F15 1 Tf 0.5 0 TD [(doba)12.2(cterium)]TJ -33.1613 -1.2266 TD (infantis)Tj /F6 1 Tf 3.3701 0 TD [(generated)-359.7(by)-359.4(multi-dimensional)-360.4(chromatography)-354.7(coupled)-359.6(with)-363.5(tandem)-357.3(mass)-360.5(spectro-)]TJ -3.3701 -1.2203 TD [(metry)59.4(,)]TJ /F15 1 Tf 2.8643 0 TD [(Pr)37.9(oteomics)]TJ /F6 1 Tf 4.5209 0 TD [(,)-331.7(i)0(n)-331.8(press.)]TJ -9.1176 -1.4416 TD [(35.)-482.5(W)30.2(ilkins,)-253.5(M.)-249.7(R.,)-250.4(Sanchez,)-248.1(J.)-250.2(C.,)-250.4(Gooley)69(,)-249.5(A)0(.)-252.3(A.,)-248.9(Appel,)-250.5(R.)-253.8(D.,)-248.9(Humphery-Smith,)-248.4(I.,)-254.6(Hochstrasser)26.7(,)]TJ 1.7325 -1.2266 TD [(D.)-321.9(F)71.5(.)0(,)-315.7(and)-323.4(W)30.2(illiams,)-319.9(K.)-315.6(L.,)-321.3(Progress)-320.9(with)-319.2(proteome)-321(projects:)-326.2(Why)-316.6(all)-325.1(proteins)-320.2(express)12.5(ed)-323.9(by)-321.5(a)]TJ 0 -1.2203 TD [(genome)-327.9(should)-324.8(be)-330.2(identi)]TJ /F3 1 Tf 10.0608 0 TD ()Tj /F6 1 Tf 0.552 0 TD [(e)13.7(d)-328.3(and)-323.4(ho)19.9(w)-325.3(t)0(o)-325.5(d)0(o)-327.8(it,)]TJ /F15 1 Tf 8.6278 0 TD [(Biotechn)10.1(ol.)-328.4(Genet.)-328.8(Eng)14.3(.)-325.4(Rev)79(.)]TJ /F6 1 Tf 12.0704 0 TD (1996,)Tj /F17 1 Tf 2.5734 0 TD (13)Tj /F6 1 Tf 0.999 0 TD 0.3254 Tc [(,1)325.4(9)]TJ /F3 1 Tf 1.5754 0 TD 0 Tc ()Tj /F6 1 Tf 0.5 0 TD (50.)Tj -38.6913 -1.4416 TD [(36.)-482.5(Hatzimanikatis,)-274.2(V)123.6(.)0(,)-271.4(and)-266.5(Lee,)-271.7(K.)-271.3(H.,)-267.9(Dynamical)-270.7(analysis)-276.9(of)-267.2(gene)-268.5(networks)-275.2(requires)-270.6(both)-267.7(mRN)27.8(A)]TJ 1.7325 -1.2266 TD [(and)-336.1(protein)-332.1(expressio)9.5(n)-334.6(information,)]TJ /F15 1 Tf 14.8841 0 TD [(Metab)31.8(.)-331.7(Eng.)]TJ /F6 1 Tf 5.2986 0 TD (1999,)Tj /F17 1 Tf 2.5861 0 TD (1)Tj /F6 1 Tf 0.4995 0 TD [(\(4\),)-335.5(275)]TJ /F3 1 Tf 3.2514 0 TD ()Tj /F6 1 Tf 0.5 0 TD (281.)Tj -28.7522 -1.4416 TD [(37.)-482.5(Futcher)31.3(,)-281.1(B.,)-275.6(Latter)25.5(,)-274.8(G)0(.)-284(I.,)-273.5(Monardo,)-283.5(P)103.1(.)0(,)-277.7(McLaughlin,)-277.1(C.)-279(S.,)-275.8(and)-279.2(Garrels,)-283.7(J.)-275.5(I.,)-279.8(A)-281(sampling)-276.9(of)-279.8(the)]TJ 1.7325 -1.2203 TD [(yeast)-336.4(proteome,)]TJ /F15 1 Tf 6.7718 0 TD [(Mol.)-330.1(Cell.)-338.6(Biol.)]TJ /F6 1 Tf 6.7149 0 TD (1999,)Tj /F17 1 Tf 2.5861 0 TD (19)Tj /F6 1 Tf 0.999 0 TD [(\(11\),)-335(7357)]TJ /F3 1 Tf 4.2509 0 TD ()Tj /F6 1 Tf 0.5 0 TD (7368.)Tj -23.5552 -1.4479 TD [(38.)-482.5(V)104.7(elculescu,)-510.7(V)130(.)-502.4(E.,)-504.7(Zhang,)-502.3(L,)-501.8(V)123.6(ogelstein,)-503.5(B.,)-503.3(and)-500.5(Kinzler)28.9(,)-502.4(K)0(.)-505.2(W)80.8(.,)-499(Serial)-504.4(analysis)-504.6(of)-501.1(gene)]TJ 1.7325 -1.2203 TD [(expressio)9.5(n,)]TJ /F15 1 Tf 4.856 0 TD (Science)Tj /F6 1 Tf 3.4017 0 TD (1995,)Tj /F17 1 Tf 2.5861 0 TD (270)Tj /F6 1 Tf 1.4985 0 TD [(\(5235\),)-334(484)]TJ /F3 1 Tf 4.7499 0 TD ()Tj /F6 1 Tf 0.5 0 TD (487.)Tj -19.3247 -1.4479 TD [(39.)-482.5(Gygi,)-413(S.)-405.7(P)103.1(.)0(,)-410.5(Corthals,)-410.1(G.)-410.4(L.,)-409.8(Zhang,)-413.7(Y)123.6(.)0(,)-404.2(Rochon,)-411.8(Y)123.6(.)0(,)-410.5(and)-412(Aebersold,)-412.9(R.,)-408.4(Ev)20.1(aluation)-411.4(of)-406.3(two-)]TJ 1.7325 -1.2203 TD [(dimensional)-199.7(gel)-201(electrophoresis-based)-198.5(proteome)-200.8(analysis)-201.1(technology)61.5(,)]TJ /F15 1 Tf 27.6691 0 TD [(Pr)44.2(oc.)-200.4(Natl.)-197.1(Acad.)-192.9(Sci.)-197.6(USA)]TJ /F6 1 Tf -27.6691 -1.2203 TD (2000,)Tj /F17 1 Tf 2.5861 0 TD (97)Tj /F6 1 Tf 0.999 0 TD [(,)-331.7(9390)]TJ /F3 1 Tf 2.5817 0 TD ()Tj /F6 1 Tf 0.5 0 TD (9395.)Tj -8.3992 -1.4479 TD [(40.)-482.5(Holland,)-215.6(M.)-211.8(J.,)-215.2(T)32.3(ranscript)-217.3(abun)12.2(dance)-219.8(in)-199.1(yeast)-216.3(v)19.5(aries)-212.6(ov)19.9(er)-212.7(six)-218.7(orders)-214.6(of)-210.3(magnitude,)]TJ /F15 1 Tf 34.3334 0 TD [(J)23.4(.)-211.6(Biol.)-217.5(Chem.)]TJ /F6 1 Tf -32.6009 -1.2203 TD (2002,)Tj /F17 1 Tf 2.5861 0 TD (277)Tj /F6 1 Tf 1.4985 0 TD [(\(17\),)-335(14363)]TJ /F3 1 Tf 4.7509 0 TD ()Tj /F6 1 Tf 0.5 0 TD (14366.)Tj -11.068 -1.4416 TD [(41.)-482.5(Rigaut,)-242.8(G.,)-242.6(She)19.4(vchenko,)-238.3(A.,)-242.6(Rutz,)-239.8(B.,)-237.7(W)30.2(ilm,)-240.7(M.,)-240(Mann,)-244.4(M.,)-240(and)-241.2(Seraphin,)-243.1(B.,)-237.7(A)-243.1(generic)-244.4(protein)]TJ 1.7325 -1.2266 TD (puri)Tj /F3 1 Tf 1.614 0 TD ()Tj /F6 1 Tf 0.552 0 TD [(cation)-543.9(method)-550.9(for)-547.5(protein)-553.4(complex)-540.1(characterization)-561.6(and)-551.1(proteome)-548.6(exploration,)]TJ /F15 1 Tf 34.3489 0 TD (Nat.)Tj -36.5148 -1.2203 TD [(Biotechn)10.1(ol)]TJ /F6 1 Tf 4.3438 0 TD [(.)-331.7(1999,)]TJ /F17 1 Tf 3.1678 0 TD (17)Tj /F6 1 Tf 0.999 0 TD [(\(10\),)-335(1030)]TJ /F3 1 Tf 4.2509 0 TD ()Tj /F6 1 Tf 0.5 0 TD (1032.)Tj -14.994 -1.4416 TD [(42.)-482.5(Ikeda,)-241.9(M.,)-246.3(and)-241.2(Nakaga)11.3(wa,)-241.6(S.,)-244.2(The)]TJ /F15 1 Tf 15.5733 0 TD [(Corynebacterium)-248.5(glutamicum)]TJ /F6 1 Tf 12.2222 0 TD [(genome:)-243(Features)-243.7(and)-241.2(impacts)]TJ -26.063 -1.2266 TD [(on)-334.1(biotechnological)-338.2(processes,)]TJ /F15 1 Tf 12.7786 0 TD [(Appl.)-333.6(Micr)36.4(obiol.)-331(Biotechn)10.1(ol.)]TJ /F6 1 Tf 11.9566 0 TD (2003,)Tj /F17 1 Tf 2.5861 0 TD (62)Tj /F6 1 Tf 0.999 0 TD (\(2)Tj /F3 1 Tf 0.833 0 TD ()Tj /F6 1 Tf 0.5 0 TD [(3\),)-334.5(99)]TJ /F3 1 Tf 2.4175 0 TD ()Tj /F6 1 Tf 0.5 0 TD (109.)Tj -34.3032 -1.4416 TD [(43.)-482.5(Kalino)20.8(wski,)-192.9(J.,)-189.9(Bathe,)-184.8(B.,)-193.4(Bartels,)-191.6(D.,)-185.7(Bischof)20(f,)-188.4(N.,)-192(Bott,)-184.5(M.,)-189.4(Burkovski,)-181.8(A.,)-185.7(Dusch,)-190.8(N.,)-192(Eggeling,)]TJ 1.7325 -1.2266 TD [(L.,)-308.7(Eikmanns,)-313.5(B.)-310.7(J.,)-310(Gaigalat,)-312.5(L.,)-315(Goesmann,)-309.1(A.,)-312.2(Hartmann,)-308.2(M.,)-315.9(Huthmacher)28.4(,)-306.4(K.,)-312.2(Kramer)30.3(,)-312.7(R.,)]TJ 0 -1.2203 TD [(Linke,)-215.4(B.,)-218.7(McHardy)61.5(,)-217.9(A)0(.)-214.4(C.,)-218.7(Meyer)38.5(,)-217.9(F)77.8(.,)-220.8(Mockel,)-218.2(B.,)-212.4(Pfef)21(ferle,)-223.2(W)87.1(.)0(,)-220.8(Puhler)33.2(,)-217.9(A.,)-217.3(Re)12.8(y)63.7(,)-217.9(D.)-220.7(A.,)-211(Ruckert,)]TJ T* [(C.,)-579.1(Rupp,)-581.1(O.,)-577.7(Sahm,)-580.9(H.,)-577.7(W)74.4(endisch,)-585(V)130(.)-578.3(F)71.5(.)0(,)-581.2(W)30.2(ie)13.5(grabe,)-583.3(I.,)-577(and)-582.7(T)76.6(auch,)-581.2(A.,)-577.7(The)-582.5(complete)]TJ /F15 1 Tf T* [(Corynebacterium)-267.5(glutamicum)]TJ /F6 1 Tf 12.2538 0 TD [(A)98.4(TCC)-260.7(13032)-256.8(genome)-258.4(sequence)-266.2(and)-260.2(its)-260.7(impact)-260.1(on)-258.3(the)-257.9(production)]TJ -12.2538 -1.2266 TD (of)Tj 6.2762 0 0 6.2762 80.2205 117.2409 Tm (L)Tj 8.9663 0 0 8.9663 84.0756 117.2409 Tm [(-aspartate-deri)15.8(v)13.1(e)0(d)-336.6(amino)-330(acids)-336.4(and)-336.1(vitamins,)]TJ /F15 1 Tf 18.6083 0 TD [(J)17(.)-331.7(Biotechn)10.1(ol.)]TJ /F6 1 Tf 5.9372 0 TD (2003,)Tj /F17 1 Tf 2.5797 0 TD (104)Tj /F6 1 Tf 1.5049 0 TD (\(1)Tj /F3 1 Tf 0.833 0 TD ()Tj /F6 1 Tf 0.5 0 TD [(3\),)-328.2(5)]TJ /F3 1 Tf 1.9112 0 TD ()Tj /F6 1 Tf 0.5 0 TD (25.)Tj -35.7064 -1.4416 TD [(44.)-482.5(Hayashi,)-259.5(M.,)-252.7(Mizoguchi,)-252.4(H.,)-255.3(Shiraishi,)-255.7(N.,)-248.9(Obayashi,)-259(M.,)-252.7(Nakagaw)8.5(a,)-257.8(S.,)-250.5(Imai,)-253.8(J.,)-253.1(W)68.1(atanabe,)-253.5(S.,)]TJ 1.7325 -1.2203 TD [(Ota,)-453.8(T)70.2(.)0(,)-454.8(and)-456.2(Ikeda,)-456.9(M.,)-455(T)32.3(ranscriptome)-455.7(analysis)-460.3(of)-450.6(acetate)-459.3(metabolism)-456.6(in)]TJ /F15 1 Tf 31.2036 0 TD (Corynebacterium)Tj /F12 1 Tf 6.9738 0 0 6.9738 337.6062 669.7699 Tm [(REFER)-16(ENCES)]TJ /F11 1 Tf 8.9663 0 0 8.9663 402.4629 669.7699 Tm (13)Tj ET endstream endobj 44 0 obj > endobj 45 0 obj > /ExtGState > >> endobj 46 0 obj > stream BT /F15 1 Tf 8.9663 0 0 8.9663 107.6031 640.2896 Tm 0 g /GS2 gs 0 Tc 0 Tw (glutamicum)Tj /F6 1 Tf 4.9445 0 TD [(using)-211.4(a)-216.9(n)0(e)17.5(wly)-214.5(de)23.8(veloped)-207.8(metabolic)-220.8(array)61.9(,)]TJ /F15 1 Tf 16.6356 0 TD [(Biosci.)-220.1(Biotechn)10.1(ol.)-214.6(Biochem.)]TJ /F6 1 Tf 11.748 0 TD (2002,)Tj /F17 1 Tf 2.4659 0 TD (66)Tj /F6 1 Tf 0.999 0 TD (\(6\),)Tj -36.793 -1.2203 TD (1337)Tj /F3 1 Tf 2 0 TD ()Tj /F6 1 Tf 0.5 0 TD (1344.)Tj -4.2324 -1.448 TD [(45.)-482.5(Krmer)32.2(,)-186.3(J)0(.)-187(O.,)-185.7(Sor)12.9(genfrei,)-184.3(O.,)-185.7(Klopprogge,)-187.5(K.,)-185.7(Heinzle,)-188.9(E.,)-182.2(and)-184.3(W)30.2(ittmann,)-188.3(C.,)-180.8(In-depth)-191.1(pro)]TJ /F3 1 Tf 36.8235 0 TD ()Tj /F6 1 Tf 0.5386 0 TD [(ling)-183.1(of)]TJ -35.6296 -1.2203 TD (lysine-producing)Tj /F15 1 Tf 7.2461 0 TD [(Corynebacterium)-463.5(glutamicum)]TJ /F6 1 Tf 12.6585 0 TD [(by)-454.3(combined)-457.5(analysis)-460.3(of)-463.2(the)-460.2(transcriptome,)]TJ -19.9045 -1.2203 TD [(metabolome,)-336.6(and)]TJ /F3 1 Tf 7.3283 0 TD ()Tj /F6 1 Tf 0.552 0 TD (uxome,)Tj /F15 1 Tf 3.3176 0 TD [(J)23.4(.)-331.7(Bacteriol.)]TJ /F6 1 Tf 5.3302 0 TD (2004,)Tj /F17 1 Tf 2.5797 0 TD (186)Tj /F6 1 Tf 1.5049 0 TD [(\(6\),)-329.1(1769)]TJ /F3 1 Tf 3.7451 0 TD ()Tj /F6 1 Tf 0.5 0 TD (1784.)Tj -26.5902 -1.4479 TD [(46.)-482.5(Hermann,)-197.2(T)76.6(.)0(,)-195.5(Pfef)21(ferle,)-191.6(W)80.8(.)0(,)-195.5(Baumann,)-189.7(C.,)-193.4(Busker)29.9(,)-192.6(E.,)-194.9(Schaf)21.7(fer)25.4(,)-192.6(S.,)-187.3(Bott,)-197.1(M.,)-189.4(Sahm,)-195.2(H.,)-192(Dusch,)-190.8(N.,)]TJ 1.7325 -1.2203 TD [(Kalino)20.8(wski,)-300.4(J.,)-297.4(Puhler)26.9(,)-293.8(A.,)-299.5(Bendt,)-302.5(A.)-296.6(K.,)-299.5(Kramer)30.3(,)-300.1(R.,)-300.9(and)-298.1(Burko)14.1(vski,)-303.4(A.,)-299.5(Proteome)-300.6(analysis)-295.9(of)]TJ /F15 1 Tf T* [(Corynebacterium)-337(glutamicum)]TJ /F6 1 Tf 12.0704 0 TD (,)Tj /F15 1 Tf 0.5817 0 TD [(Electr)39.6(ophor)26.5(esis)]TJ /F6 1 Tf 6.2723 0 TD [(,)-331.7(2001,)]TJ /F17 1 Tf 3.1678 0 TD (22)Tj /F6 1 Tf 0.999 0 TD [(\(9\),)-329.1(1712)]TJ /F3 1 Tf 3.7451 0 TD ()Tj /F6 1 Tf 0.5 0 TD (1723.)Tj -29.0688 -1.4479 TD [(47.)-482.5(Bendt,)-233(A.)-239.7(K.,)-230(Burkovski,)-226.1(A.,)-236.3(Schaf)15.4(fer)31.8(,)-236.9(S.,)-231.6(Bott,)-235.1(M.,)-233.7(and)-234.9(Farwick,)-227.9(M.,)-233.7(and)-234.9(Hermann,)-241.5(T)76.6(.)0(,)-233.5(T)70.2(o)19.5(wards)]TJ 1.7325 -1.2203 TD [(a)-286.5(phosphoproteome)-293.5(map)-289(of)]TJ /F15 1 Tf 11.3433 0 TD [(Corynebacterium)-292.8(glutamicum)]TJ /F6 1 Tf 12.0262 0 TD (,)Tj /F15 1 Tf 0.5374 0 TD [(Pr)37.9(oteomics)]TJ /F6 1 Tf 4.8117 0 TD (2003,)Tj /F17 1 Tf 2.5355 0 TD (3)Tj /F6 1 Tf 0.4995 0 TD [(\(8\),)-291.2(1637)]TJ /F3 1 Tf 3.7071 0 TD ()Tj /F6 1 Tf 0.5 0 TD (1646.)Tj -37.6933 -1.4416 TD [(48.)-482.5(Hermann,)-298.4(T)76.6(.)0(,)-296.7(Finkemeier)29.1(,)-300.1(M.,)-296.9(Pfef)21(ferle,)-299.1(W)87.1(.)0(,)-296.7(W)74.4(ersch,)-300(G.,)-299.5(Kramer)30.3(,)-293.8(R.,)-294.6(and)-298.1(Burkovski,)-289.3(A.,)-293.2(T)70.2(wo-)]TJ 1.7325 -1.2266 TD [(dimensional)-332.5(electrophoretic)-342.3(analysis)-333.9(of)]TJ /F15 1 Tf 16.3321 0 TD [(Corynebacterium)-337(glutamicum)]TJ /F6 1 Tf 12.3992 0 TD [(membrane)-335.5(fraction)-336.7(and)]TJ -28.7313 -1.2203 TD [(surface)-339.1(proteins.)]TJ /F15 1 Tf 7.0374 0 TD [(Electr)33.3(ophor)32.8(esis)]TJ /F6 1 Tf 6.6074 0 TD (2000,)Tj /F17 1 Tf 2.5798 0 TD (21)Tj /F6 1 Tf 0.999 0 TD [(\(3\),)-335.5(654)]TJ /F3 1 Tf 3.2514 0 TD ()Tj /F6 1 Tf 0.5 0 TD (659.)Tj -22.7075 -1.4479 TD [(49.)-482.5(Barr)27.5(,)-331.7(M)0(.)-331.9(M.,)-334.9(Super)-336.3(models,)]TJ /F15 1 Tf 13.3982 0 TD [(Physiol)-330.5(Genomics)]TJ /F6 1 Tf 7.676 0 TD (2003,)Tj /F17 1 Tf 2.5798 0 TD (13)Tj /F6 1 Tf 0.999 0 TD [(\(1\),)-335.5(15)]TJ /F3 1 Tf 2.7514 0 TD ()Tj /F6 1 Tf 0.5 0 TD (24.)Tj -27.9044 -1.4416 TD [(50.)-482.5(Hutchison,)-215.9(C.)-209.5(A.,)-217.3(Peterson,)-212.6(S.)-216(N.,)-211(Gill,)-218.7(S.)-209.7(R.,)-212.4(Cline,)-218(R.)-209.5(T)70.2(.)0(,)-214.5(White,)-215.2(O.,)-211(Fraser)24.7(,)-211.6(C)0(.)-215.8(M.,)-208.4(Smith,)-213(H.)-214.4(O.,)]TJ 1.7325 -1.2203 TD [(and)-272.9(V)104.7(enter)28.9(,)-268.5(J)0(.)-269.2(C.,)-269.3(Global)-270.1(transposon)-272.2(mutagenesis)-275.1(and)-272.9(a)-267.5(minimal)]TJ /F15 1 Tf 26.0567 0 TD (Mycoplasma)Tj /F6 1 Tf 5.3871 0 TD (genome.)Tj /F15 1 Tf 3.6926 0 TD (Science)Tj /F6 1 Tf -35.1364 -1.2266 TD (1999,)Tj /F17 1 Tf 2.5797 0 TD (286)Tj /F6 1 Tf 1.5049 0 TD [(\(5447\),)-334(2089)]TJ /F3 1 Tf 5.2499 0 TD ()Tj /F6 1 Tf 0.5 0 TD (2090.)Tj -11.567 -1.4416 TD [(51.)-482.5(K)28.8(oonin,)-364.9(E.)-375.3(V)123.6(.)0(,)-366.2(H)0(o)16.6(w)-369.5(many)-358.1(genes)-376.7(can)-370.1(make)-373.2(a)-368.7(cell:)-374.9(the)-371.7(minimal-gene-set)-372.9(concept,)]TJ /F15 1 Tf 35.5284 0 TD [(Annu.)-373.9(Re)11.4(v)67.6(.)]TJ -33.796 -1.2203 TD [(Genomics)-335.3(Hum.)-336.9(Genet.)]TJ /F6 1 Tf 9.8321 0 TD (2000,)Tj /F17 1 Tf 2.5797 0 TD (1)Tj /F6 1 Tf 0.4995 0 TD 0.338 Tc [(,9)338(9)]TJ /F3 1 Tf 1.588 0 TD 0 Tc ()Tj /F6 1 Tf 0.5 0 TD (116.)Tj -16.7319 -1.448 TD [(52.)-482.5(Zimmer)31.2(,)-451.8(C.,)-452.7(Genomics.)-458.6(T)32.3(inker)31.3(,)-458.2(tailor:)-454(Can)-454.6(V)104.7(enter)-451.6(stitch)-455.4(together)-454.2(a)-457.2(genome)-454.4(from)-455.7(scratch?)]TJ /F15 1 Tf 1.7325 -1.2203 TD (Science)Tj /F6 1 Tf 3.408 0 TD (2003,)Tj /F17 1 Tf 2.5797 0 TD (299)Tj /F6 1 Tf 1.4985 0 TD [(\(5609\),)-334(1006)]TJ /F3 1 Tf 5.2499 0 TD ()Tj /F6 1 Tf 0.5 0 TD (1007.)Tj -14.9687 -1.4479 TD [(53.)-482.5(Schwiko)20.3(wski,)-237.1(B.,)-237.7(Uetz)-237.8(P)103.1(,)-236.9(and)-241.2(Fields,)-237.9(S.,)-237.9(A)-236.8(network)-236.6(of)-241.9(protein-protein)-236.5(interactions)-242.6(in)-224.3(yeast,)]TJ /F15 1 Tf 38.2473 0 TD (Nat.)Tj -36.5148 -1.2203 TD [(Biotechn)10.1(ol.)]TJ /F6 1 Tf 4.9256 0 TD (2000,)Tj /F17 1 Tf 2.5797 0 TD (18)Tj /F6 1 Tf 1.0053 0 TD [(\(12\),)-328.7(1257)]TJ /F3 1 Tf 4.2446 0 TD ()Tj /F6 1 Tf 0.5 0 TD (1261.)Tj -14.9877 -1.4416 TD [(54.)-482.5(Me)23.1(wes,)-261.3(H.)-265(W)87.1(.)0(,)-265.1(Hani,)-257.3(J.,)-259.5(Pfeif)17.5(fer)31.8(,)-262.2(F)71.5(.,)-258.8(and)-260.2(Frishman,)-258(D.,)-261.6(MIPS:)-261.3(A)-262.1(database)-257.6(for)-263(protein)-262.6(sequences)]TJ 1.7325 -1.2267 TD [(and)-336.1(complete)-324.8(genomes,)]TJ /F15 1 Tf 9.9333 0 TD [(Nucleic)-339.1(Acids)-333.8(Res.)]TJ /F6 1 Tf 7.9985 0 TD (1998,)Tj /F17 1 Tf 2.5861 0 TD (26)Tj /F6 1 Tf 0.999 0 TD [(\(1\),)-335.5(33)]TJ /F3 1 Tf 2.7514 0 TD ()Tj /F6 1 Tf 0.5 0 TD (37.)Tj -26.5008 -1.4416 TD [(55.)-482.5(Gof)20.8(feau,)-280.3(A.,)-286.9(F)14.6(our)-285.7(years)-278.1(of)-286.2(post-genomic)-280(life)-264(with)-281.3(6,000)-279.2(yeast)-285.8(genes,)]TJ /F15 1 Tf 29.7809 0 TD [(FEBS)-282(Lett.)]TJ /F6 1 Tf 4.7169 0 TD (2000,)Tj /F17 1 Tf 2.5292 0 TD (480)Tj /F6 1 Tf 1.4985 0 TD (\(1\),)Tj -36.793 -1.2203 TD (37)Tj /F3 1 Tf 1 0 TD ()Tj /F6 1 Tf 0.5 0 TD (41.)Tj -3.2324 -1.448 TD [(56.)-482.5(O)]TJ /F3 1 Tf 2.4505 0 TD ()Tj /F6 1 Tf 0.333 0 TD [(Far)11.9(rell,)-368.1(P)103.1(.)-363.3(H.,)-362.7(High)-365.8(resolution)-367.5(two-dimensional)-365.8(electrophoresis)-369.8(of)-368.4(proteins,)]TJ /F15 1 Tf 31.2464 0 TD [(J)23.4(.)-363.3(Biol.)-369.2(Chem.)]TJ /F6 1 Tf -32.2974 -1.2203 TD (1975,)Tj /F17 1 Tf 2.5797 0 TD (250)Tj /F6 1 Tf 1.5049 0 TD [(\(10\),)-328.7(4007)]TJ /F3 1 Tf 4.2446 0 TD ()Tj /F6 1 Tf 0.5 0 TD (4021.)Tj -10.5617 -1.4479 TD [(57.)-482.5(Sundararaj,)-266.1(S.,)-256.9(Guo,)-264(A.,)-261.6(Habibi-Nazhad,)-263.9(B.,)-263(Rouani,)-264.1(M.,)-259(Stothard,)-263.6(P)103.1(.)0(,)-258.8(Ellison,)-259.2(M.,)-265.3(and)-260.2(W)30.2(ishart,)]TJ 1.7325 -1.2203 TD [(D.)-233.4(S.,)-231.6(The)-234.7(CyberCell)-241.9(Database)-235.6(\(CCDB\):)-238.3(A)-230.4(comprehensi)12(v)13.1(e)0(,)-232.5(self-updating,)-241.2(relational)-236.1(database)-238.6(to)]TJ T* [(coordinate)-341.9(and)-336.1(facilitate)-343.7(in)-331.8(silico)-341.6(modeling)-338.9(of)]TJ /F15 1 Tf 19.1584 0 TD [(Esch)11.2(erichia)-333.1(coli)]TJ /F6 1 Tf 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Table of Contents

PREFACE.

ACKNOWLEDGMENTS.

CONTRIBUTORS.

PART I: GENERAL PROTEOMICS OF MICROORGANISMS/MODEL ORGANISMS.

1. Holistic Biology of Microorganisms: Genomics, Transcriptomics, and Proteomics (Valerie Wasinger).

2. Strategies for Measuring Dynamics: The Temporal Component of Proteomics (Robert J. Beynon and Julie M. Pratt).

3. Quest for Complete Proteome Coverage (C. David O’Connor, Ian N. Clarke, and Paul Skipp).

4. Proteome of Mycoplasma pneumoniae (Richard Herrmann and Thomas Ruppert).

5. Proteomics of Archaea (Ricardo Cavicchioli, Amber Goodchild, and Mark Raftery).

PART II: PROTEOMICS AND CELL PHYSIOLOGY.

6. Elucidation of Mechanisms of Acid Stress in Listeria monocytogenes by Proteomic Analysis (Luu Phan-Thanh and Lothar Jänsch).

7. Oxidation of Bacterial Proteome in Response to Starvation (Thomas Nyström).

8. Tale of Two Metal Reducers: Comparative Proteome Analysis of Geobacter sulferreducens PCA and Shewanella oneidensis MR-1 (Carol S. Giometti).

9. AMT Tag Approach to Proteomic Characterization of Deinococcus radiodurans and Shewanella oneidensis (Mary S. Lipton, Margaret F. Romine, Matthew E. Monroe, Dwayne A. Elias, Ljiljana Pasa-Tolic, Gordon A. Anderson, David J. Anderson, Jim Fredrickson, Kim K. Hixson, Christophe Masselon, Heather Mottaz, Nikola Tolic, and Richard D. Smith).

PART III: PHYSIOLOGICAL PROTEOMICS OF INDUSTRIAL BACTERIA.

10. Proteomics of Corynebacterium glutamicum: Essential Industrial Bacterium (Andreas Burkovski).

11. Proteomics of Lactococcus lactis: Phenotypes for a Domestic Bacterium (Mogens Kilstrup).

12. Proteomic Survey through Secretome of Bacillus subtilis (Haike Antelmann, Jan Maarten van Dijl, Sierd Bron, and Michael Hecker).

PART IV: PROTEOMICS OF PATHOGENIC MICROORGANISMS.

13. Analyzing Bacterial Pathogenesis at Level of Proteome (Phillip Cash).

14. Unraveling Edwardsiella tarda Pathogenesis Using the Proteomics Approach (P. S. Srinivasa Rao, Yuen Peng Tan, Jun Zheng, and Ka Yin Leung).

15. Structural Proteomics and Computational Analysis of a Deadly Pathogen: Combating Mycobacterium tuberculosis from Multiple Fronts (Michael Strong and Celia W. Goulding).

16. Proteomic Studies of Plant-Pathogenic Oomycetes and Fungi (Catherine R. Bruce, Pieter van West, and Laura J. Grenville-Briggs).

17. Candida albicans Biology and Pathogenicity: Insights from Proteomics (Aida Pitarch, Ce´sar Nombela, and Concha Gil).

18. Contributions of Proteomics to Diagnosis, Treatment, and Prevention of Candidiasis (Aida Pitarch, Ce´sar Nombela, and Concha Gil).

19. Identification of Protein Candidates for Developing Bacterial Ghost Vaccines against Brucella (Vito G. Delvecchio, Tim Alefantis, Rodolfo A. Ugalde, Diego Comerci, Maria Ines Marchesini, Akbar Khan, Werner Lubitz, and Cesar V. Mujer).

20. Genomics and Proteomics in Reverse Vaccines (Guido Grandi).

PART V: PROTEOME DATABASES, BIOINFORMATICS, AND BIOCHEMICAL MODELING.

21. Databases and Resources for in silico Proteome Analysis (Manuela Pruess, Paul Kersey, Tamara Kulikova, and Rolf Apweiler).

22. Interspecies and Intraspecies Comparison of Microbial Proteins: Learning about Gene Ancestry, Protein Function, and Species Life Style (Bernard Labedan and Olivier Lespinet).

23. Cellular Kinetic Modeling of the Microbial Metabolism (Igor I. Goryanin, Galina V. Lebedeva, Ekaterina A. Mogilevskaya, Eugeniy A. Metelkin, and Oleg V. Demin).

INDEX.