Characterization of early autophagy signaling by quantitative phosphoproteomics

Autophagy

Volumn 10, Issue 2, 2014, Pages 356-371

  Rigbolt, Kristoffer T G ^a   Zarei, Mostafa ^a   Sprenger, Adrian ^a,b   Becker, Andrea C ^a   Diedrich, Britta ^a   Huang, Xun ^a   Eiselein, Sven ^a   Kristensen, Anders R ^c   Gretzmeier, Christine ^a   Andersen, JensS ^d   Zi, Zhike ^a   Dengjel, Jor̈n ^a,b  

^a UNIVERSITY OF FREIBURG   (Germany)

^b UNIVERSITY OF FREIBURG   (Germany)

^c UNIVERSITY OF BRITISH COLUMBIA   (Canada)

^d UNIVERSITY OF SOUTHERN DENMARK   (Denmark)

Author keywords

Autophagy; Bioinformatics; Mass spectrometry; Phosphoproteomics; Phosphorylation; Proteomics; Signal transduction

Indexed keywords

MAMMALIAN TARGET OF RAPAMYCIN; PHOSPHOPROTEIN; PROTEIN KINASE;

ARTICLE; AUTOPHAGY; HUMAN; MOLECULAR DYNAMICS; NONHUMAN; PHOSPHOPROTEOMICS; PROTEIN ANALYSIS; PROTEIN DEPHOSPHORYLATION; PROTEIN PHOSPHORYLATION; PROTEIN PROTEIN INTERACTION; PROTEOMICS; QUANTITATIVE ANALYSIS; REGULATORY MECHANISM; SIGNAL TRANSDUCTION;

AUTOPHAGY; BIOINFORMATICS; MASS SPECTROMETRY; PHOSPHOPROTEOMICS; PHOSPHORYLATION; PROTEOMICS; SIGNAL TRANSDUCTION;

AUTOPHAGY; CELL LINE, TUMOR; HUMANS; PHOSPHOPROTEINS; PHOSPHORYLATION; PROTEOMICS; SIGNAL TRANSDUCTION; SIROLIMUS; STARVATION; TIME FACTORS;

EID: 84894452623     PISSN: 15548627     EISSN: 15548635     Source Type: Journal    
DOI: 10.4161/auto.26864     Document Type: Article

References (76)

1. Rabinowitz JD, White E. Autophagy and metabolism. Science 2010; 330:1344-8; PMID:21127245; http://dx.doi.org/10.1126/science.1193497
2. De Duve C, Wattiaux R. Functions of lysosomes. Annu Rev Physiol 1966; 28:435-92; PMID:5322983; http://dx.doi.org/10.1146/annurev.ph.28.030166.002251
3. Klionsky DJ. Autophagy: from phenomenology to molecular understanding in less than a decade. Nat Rev Mol Cell Biol 2007; 8:931-7; PMID:17712358; http://dx.doi.org/10.1038/nrm2245
4. He C, Klionsky DJ. Regulation mechanisms and signaling pathways of autophagy. Annu Rev Genet 2009; 43:67-93; PMID:19653858; http://dx.doi.org/10. 1146/annurev-genet-102808-114910
5. Johansen T, Lamark T. Selective autophagy mediated by autophagic adapter proteins. Autophagy 2011; 7:279-96; PMID:21189453; http://dx.doi.org/10.4161/ auto.7.3.14487
6. Randow F, Münz C. Autophagy in the regulation of pathogen replication and adaptive immunity. Trends Immunol 2012; 33:475-87; PMID:22796170; http://dx.doi.org/10.1016/j.it.2012.06.003
7. Dumit VI, Dengjel J. Autophagosomal protein dynamics and influenza virus infection. Front Immunol 2012; 3:43; PMID:22566925; http://dx.doi.org/10.3389/ fimmu.2012.00043
8. White E. Deconvoluting the context-dependent role for autophagy in cancer. Nat Rev Cancer 2012; 12:401-10; PMID:22534666; http://dx.doi.org/10. 1038/nrc3262
9. Mizushima N. The role of the Atg1/ULK1 complex in autophagy regulation. Curr Opin Cell Biol 2010; 22:132-9; PMID:20056399; http://dx.doi.org/10.1016/j. ceb.2009.12.004
10. Chan EY. Regulation and function of uncoordinated-51 like kinase proteins. Antioxid Redox Signal 2012; 17:775-85; PMID:22074133; http://dx.doi.org/10.1089/ars.2011.4396
11. Egan DF, Shackelford DB, Mihaylova MM, Gelino S, Kohnz RA, Mair W, Vasquez DS, Joshi A, Gwinn DM, Taylor R, et al. Phosphorylation of ULK1 (hATG1) by AMP-activated protein kinase connects energy sensing to mitophagy. Science 2011; 331:456-61; PMID:21205641; http://dx.doi.org/10.1126/science.1196371
12. Blommaart EF, Luiken JJ, Blommaart PJ, van Woerkom GM, Meijer AJ. Phosphorylation of ribosomal protein S6 is inhibitory for autophagy in isolated rat hepatocytes. J Biol Chem 1995; 270:2320-6; PMID:7836465; http://dx.doi.org/10.1074/jbc.270.5.2320
13. Neufeld TP. TOR-dependent control of autophagy: biting the hand that feeds. Curr Opin Cell Biol 2010; 22:157-68; PMID:20006481; http://dx.doi.org/10. 1016/j.ceb.2009.11.005
14. Zimmermann AC, Zarei M, Eiselein S, Dengjel J. Quantitative proteomics for the analysis of spatiotemporal protein dynamics during autophagy. Autophagy 2010; 6:1009-16; PMID:20603599; http://dx.doi.org/10.4161/auto.6.8.12786
15. Dengjel J, Høyer-Hansen M, Nielsen MO, Eisenberg T, Harder LM, Schandorff S, Farkas T, Kirkegaard T, Becker AC, Schroeder S, et al. Identification of autophagosome-associated proteins and regulators by quantitative proteomic analysis and genetic screens. Mol Cell Proteomics 2012; 11:014035; PMID:22311637; http://dx.doi.org/10.1074/mcp.M111.014035
16. Engelke R, Becker AC, Dengjel J. The degradative inventory of the cell: proteomic insights. Antioxid Redox Signal 2012; 17:803-12; PMID:22074050; http://dx.doi.org/10.1089/ars.2011.4393
17. Kristensen AR, Schandorff S, Høyer-Hansen M, Nielsen MO, Jäättelä M, Dengjel J, Andersen JS. Ordered organelle degradation during starvation-induced autophagy. Mol Cell Proteomics 2008; 7:2419-28; PMID:18687634; http://dx.doi.org/10.1074/mcp.M800184-MCP200
18. Behrends C, Sowa ME, Gygi SP, Harper JW. Network organization of the human autophagy system. Nature 2010; 466:68-76; PMID:20562859; http://dx.doi.org/10.1038/nature09204
19. Macek B, Mann M, Olsen JV. Global and site-specific quantitative phosphoproteomics: principles and applications. Annu Rev Pharmacol Toxicol 2009; 49:199-221; PMID:18834307; http://dx.doi.org/10.1146/annurev.pharmtox.011008. 145606
20. Rigbolt K, Blagoev B. Quantitative phosphoproteomics to characterize signaling networks. Sem Cell Dev Biol 2012; PMID:22677334; http://dx.doi.org/10. 1016/j.semcdb.2012.05.006
21. Becker AC, Bunkenborg J, Eisenberg T, Harder LM, Schroeder S, Madeo F, Andersen JS, Dengjel J. Friend or food: different cues to the autophagosomal proteome. Autophagy 2012; 8:995-6; PMID:22572990; http://dx.doi.org/10.4161/ auto.20286
22. Han JM, Jeong SJ, Park MC, Kim G, Kwon NH, Kim HK, Ha SH, Ryu SH, Kim S. Leucyl-tRNA synthetase is an intracellular leucine sensor for the mTORC1-signaling pathway. Cell 2012; 149:410-24; PMID:22424946; http://dx.doi.org/10.1016/j.cell.2012.02.044
23. Ong S-E, Blagoev B, Kratchmarova I, Kristensen DB, Steen H, Pandey A, Mann M. Stable isotope labeling by amino acids in cell culture, SILAC, as a simple and accurate approach to expression proteomics. Mol Cell Proteomics 2002; 1:376-86; PMID:12118079; http://dx.doi.org/10.1074/mcp.M200025-MCP200
24. Rigbolt KT, Blagoev B. Proteome-wide quantitation by SILAC. Methods Mol Biol 2010; 658:187-204; PMID:20839105; http://dx.doi.org/10.1007/978-1-60761- 780-8-11
25. Rigbolt KT, Prokhorova TA, Akimov V, Henningsen J, Johansen PT, Kratchmarova I, Kassem M, Mann M, Olsen JV, Blagoev B. System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation. Sci Signal 2011; 4:rs3; PMID:21406692; http://dx.doi.org/10.1126/scisignal.2001570
26. Cox J, Mann M. MaxQuant enables high peptide identification rates, individualized p.p.b.-range mass accuracies and proteome-wide protein quantification. Nat Biotechnol 2008; 26:1367-72; PMID:19029910; http://dx.doi.org/10.1038/nbt.1511
27. Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M. Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell 2006; 127:635-48; PMID:17081983; http://dx.doi.org/10.1016/j. cell.2006.09.026
28. Prakash A, Piening B, Whiteaker J, Zhang H, Shaffer SA, Martin D, Hohmann L, Cooke K, Olson JM, Hansen S, et al. Assessing bias in experiment design for large scale mass spectrometry-based quantitative proteomics. Mol Cell Proteomics 2007; 6:1741-8; PMID:17617667; http://dx.doi.org/10.1074/mcp.M600470-MCP200
29. Schwanhäusser B, Busse D, Li N, Dittmar G, Schuchhardt J, Wolf J, Chen W, Selbach M. Global quantification of mammalian gene expression control. Nature 2011; 473:337-42; PMID:21593866; http://dx.doi.org/10.1038/nature10098
30. Boisvert F-M, Ahmad Y, Gierliñski M, Charrière F, Lamont D, Scott M, Barton G, Lamond AI. A quantitative spatial proteomics analysis of proteome turnover in human cells. Mol Cell Proteomics 2012; 11:011429; PMID:21937730; http://dx.doi.org/10.1074/mcp.M111.011429
31. Zarei M, Sprenger A, Metzger F, Gretzmeier C, Dengjel J. Comparison of ERLIC-TiO2, HILIC-TiO2, and SCX-TiO2 for global phosphoproteomics approaches. J Proteome Res 2011; 10:3474-83; PMID:21682340; http://dx.doi.org/10.1021/ pr200092z
32. Zarei M, Sprenger A, Gretzmeier C, Dengjel J. Combinatorial use of electrostatic repulsion-hydrophilic interaction chromatography (ERLIC) and strong cation exchange (SCX) chromatography for in-depth phosphoproteome analysis. J Proteome Res 2012; 11:4269-76; PMID:22768876; http://dx.doi.org/10. 1021/pr300375d
33. Yu Y, Yoon S-O, Poulogiannis G, Yang Q, Ma XM, Villén J, Kubica N, Hoffman GR, Cantley LC, Gygi SP, et al. Phosphoproteomic analysis identifies Grb10 as an mTORC1 substrate that negatively regulates insulin signaling. Science 2011; 332:1322-6; PMID:21659605; http://dx.doi.org/10.1126/science. 1199484
34. Lipinski MM, Hoffman G, Ng A, Zhou W, Py BF, Hsu E, Liu X, Eisenberg J, Liu J, Blenis J, et al. A genome-wide siRNA screen reveals multiple mTORC1 independent signaling pathways regulating autophagy under normal nutritional conditions. Dev Cell 2010; 18:1041-52; PMID:20627085; http://dx.doi.org/10.1016/ j.devcel.2010.05.005
35. Schmitt WA Jr., Raab RM, Stephanopoulos G. Elucidation of gene interaction networks through time-lagged correlation analysis of transcriptional data. Genome Res 2004; 14:1654-63; PMID:15289483; http://dx.doi.org/10.1101/gr. 2439804
36. Kazi AA, Lang CH. PRAS40 regulates protein synthesis and cell cycle in C2C12 myoblasts. Mol Med 2010; 16:359-71; PMID:20464060; http://dx.doi.org/10. 2119/molmed.2009-00168
37. Futschik ME, Carlisle B. Noise-robust soft clustering of gene expression time-course data. J Bioinform Comput Biol 2005; 3:965-88; PMID:16078370; http://dx.doi.org/10.1142/S0219720005001375
38. Lin S-Y, Li TY, Liu Q, Zhang C, Li X, Chen Y, Zhang S-M, Lian G, Liu Q, Ruan K, et al. GSK3-TIP60-ULK1 signaling pathway links growth factor deprivation to autophagy. Science 2012; 336:477-81; PMID:22539723; http://dx.doi.org/10. 1126/science.1217032
39. Miller ML, Jensen LJ, Diella F, Jørgensen C, Tinti M, Li L, Hsiung M, Parker SA, Bordeaux J, Sicheritz-Ponten T, et al. Linear motif atlas for phosphorylation-dependent signaling. Sci Signal 2008; 1:ra2; PMID:18765831; http://dx.doi.org/10.1126/scisignal.1159433
40. Schwartz D, Gygi SP. An iterative statistical approach to the identification of protein phosphorylation motifs from large-scale data sets. Nat Biotechnol 2005; 23:1391-8; PMID:16273072; http://dx.doi.org/10.1038/nbt1146
41. Linding R, Jensen LJ, Ostheimer GJ, van Vugt MA, Jørgensen C, Miron IM, Diella F, Colwill K, Taylor L, Elder K, et al. Systematic discovery of in vivo phosphorylation networks. Cell 2007; 129:1415-26; PMID:17570479; http://dx.doi.org/10.1016/j.cell.2007.05.052
42. Shao J, Prince T, Hartson SD, Matts RL. Phosphorylation of serine 13 is required for the proper function of the Hsp90 co-chaperone, Cdc37. J Biol Chem 2003; 278:38117-20; PMID:12930845; http://dx.doi.org/10.1074/jbc.C300330200
43. Myers JS, Zhao R, Xu X, Ham A-J, Cortez D. Cyclin-dependent kinase 2 dependent phosphorylation of ATRIP regulates the G2-M checkpoint response to DNA damage. Cancer Res 2007; 67:6685-90; PMID:17638878; http://dx.doi.org/10.1158/ 0008-5472.CAN-07-0495
44. Wild P, Farhan H, McEwan DG, Wagner S, Rogov VV, Brady NR, Richter B, Korac J, Waidmann O, Choudhary C, et al. Phosphorylation of the autophagy receptor optineurin restricts Salmonella growth. Science 2011; 333:228-33; PMID:21617041; http://dx.doi.org/10.1126/science.1205405
45. Zhu Y, Massen S, Terenzio M, Lang V, Chen-Lindner S, Eils R, Novak I, Dikic I, Hamacher-Brady A, Brady NR. Modulation of serines 17 and 24 in the LC3-interacting region of Bnip3 determines pro-survival mitophagy versus apoptosis. J Biol Chem 2013; 288:1099-113; PMID:23209295; http://dx.doi.org/10. 1074/jbc.M112.399345
46. Huang W, Sherman BT, Lempicki RA. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc 2009; 4:44-57; PMID:19131956; http://dx.doi.org/10.1038/nprot.2008.211
47. Jain A, Lamark T, Sjøttem E, Larsen KB, Awuh JA, Øvervatn A, McMahon M, Hayes JD, Johansen T. p62/SQSTM1 is a target gene for transcription factor NRF2 and creates a positive feedback loop by inducing antioxidant response element-driven gene transcription. J Biol Chem 2010; 285:22576-91; PMID:20452972; http://dx.doi.org/10.1074/jbc.M110.118976
48. English L, Chemali M, Duron J, Rondeau C, Laplante A, Gingras D, Alexander D, Leib D, Norbury C, Lippé R, et al. Autophagy enhances the presentation of endogenous viral antigens on MHC class I molecules during HSV-1 infection. Nat Immunol 2009; 10:480-7; PMID:19305394; http://dx.doi.org/10.1038/ ni.1720
49. Evankovich J, Zhang R, Cardinal JS, Zhang L, Chen J, Huang H, Beer-Stolz D, Billiar TR, Rosengart MR, Tsung A. Calcium/calmodulin-dependent protein kinase IV limits organ damage in hepatic ischemia-reperfusion injury through induction of autophagy. Am J Physiol Gastrointest Liver Physiol 2012; 303:G189-98; PMID:22575222; http://dx.doi.org/10.1152/ajpgi.00051.2012
50. +/calmodulin-dependent kinase (CaMK) signaling via CaMKI and AMP-activated protein kinase contributes to the regulation of WIPI-1 at the onset of autophagy. Mol Pharmacol 2011; 80:1066-75; PMID:21896713; http://dx.doi.org/10.1124/mol.111.071761
51. Munafó DB, Colombo MI. A novel assay to study autophagy: regulation of autophagosome vacuole size by amino acid deprivation. J Cell Sci 2001; 114:3619-29; PMID:11707514
52. Marambio P, Toro B, Sanhueza C, Troncoso R, Parra V, Verdejo H, García L, Quiroga C, Munafo D, Díaz-Elizondo J, et al. Glucose deprivation causes oxidative stress and stimulates aggresome formation and autophagy in cultured cardiac myocytes. Biochim Biophys Acta 2010; 1802:509-18; PMID:20176105; http://dx.doi.org/10.1016/j.bbadis.2010.02.002
53. Lum JJ, Bauer DE, Kong M, Harris MH, Li C, Lindsten T, Thompson CB. Growth factor regulation of autophagy and cell survival in the absence of apoptosis. Cell 2005; 120:237-48; PMID:15680329; http://dx.doi.org/10.1016/j. cell.2004.11.046
54. Lee IH, Cao L, Mostoslavsky R, Lombard DB, Liu J, Bruns NE, Tsokos M, Alt FW, Finkel T. A role for the NAD-dependent deacetylase Sirt1 in the regulation of autophagy. Proc Natl Acad Sci U S A 2008; 105:3374-9; PMID:18296641; http://dx.doi.org/10.1073/pnas.0712145105
55. Eisenberg T, Knauer H, Schauer A, Büttner S, Ruckenstuhl C, Carmona-Gutierrez D, Ring J, Schroeder S, Magnes C, Antonacci L, et al. Induction of autophagy by spermidine promotes longevity. Nat Cell Biol 2009; 11:1305-14; PMID:19801973; http://dx.doi.org/10.1038/ncb1975
56. Dai D-F, Rabinovitch P. Mitochondrial oxidative stress mediates induction of autophagy and hypertrophy in angiotensin-II treated mouse hearts. Autophagy 2011; 7:917-8; PMID:21505274; http://dx.doi.org/10.4161/auto.7.8.15813
57. Eng CH, Yu K, Lucas J, White E, Abraham RT. Ammonia derived from glutaminolysis is a diffusible regulator of autophagy. Sci Signal 2010; 3:ra31; PMID:20424262; http://dx.doi.org/10.1126/scisignal.2000911
58. Chen Y, McMillan-Ward E, Kong J, Israels SJ, Gibson SB. Oxidative stress induces autophagic cell death independent of apoptosis in transformed and cancer cells. Cell Death Differ 2008; 15:171-82; PMID:17917680; http://dx.doi.org/10. 1038/sj.cdd.4402233
59. Zhang H, Bosch-Marce M, Shimoda LA, Tan YS, Baek JH, Wesley JB, Gonzalez FJ, Semenza GL. Mitochondrial autophagy is an HIF-1-dependent adaptive metabolic response to hypoxia. J Biol Chem 2008; 283:10892-903; PMID:18281291; http://dx.doi.org/10.1074/jbc.M800102200
60. Høyvik H, Gordon PB, Berg TO, Strømhaug PE, Seglen PO. Inhibition of autophagic-lysosomal delivery and autophagic lactolysis by asparagine. J Cell Biol 1991; 113:1305-12; PMID:1904444; http://dx.doi.org/10. 1083/jcb.113.6.1305
61. Seglen PO, Gordon PB. 3-Methyladenine: specific inhibitor of autophagic/lysosomal protein degradation in isolated rat hepatocytes. Proc Natl Acad Sci U S A 1982; 79:1889-92; PMID:6952238; http://dx.doi.org/10.1073/pnas. 79.6.1889
62. Bennetzen MV, Mariño G, Pultz D, Morselli E, Færgeman NJ, Kroemer G, Andersen JS. Phosphoproteomic analysis of cells treated with longevity-related autophagy inducers. Cell Cycle 2012; 11:1827-40; PMID:22517431; http://dx.doi.org/10.4161/cc.20233
63. rd, Lee J-D. CDC25B mediates rapamycin-induced oncogenic responses in cancer cells. Cancer Res 2009; 69:2663-8; PMID:19276368; http://dx.doi.org/ 10.1158/0008-5472.CAN-08-3222
64. Hsu PP, Kang SA, Rameseder J, Zhang Y, Ottina KA, Lim D, Peterson TR, Choi Y, Gray NS, Yaffe MB, et al. The mTOR-regulated phosphoproteome reveals a mechanism of mTORC1-mediated inhibition of growth factor signaling. Science 2011; 332:1317-22; PMID:21659604; http://dx.doi.org/10.1126/science.1199498
65. Wilkinson S, Croft DR, O'Prey J, Meedendorp A, O'Prey M, Dufès C, Ryan KM. The cyclin-dependent kinase PITSLRE/CDK11 is required for successful autophagy. Autophagy 2011; 7:1295-301; PMID:21808150; http://dx.doi.org/10.4161/ auto.7.11.16646
66. Capparelli C, Chiavarina B, Whitaker-Menezes D, Pestell TG, Pestell RG, Hulit J, Andò S, Howell A, Martinez-Outschoorn UE, Sotgia F, et al. CDK inhibitors (p16/p19/p21) induce senescence and autophagy in cancer-associated fibroblasts, "fueling" tumor growth via paracrine interactions, without an increase in neo-angiogenesis. Cell Cycle 2012; 11:3599-610; PMID:22935696; http://dx.doi.org/10.4161/cc.21884
67. Furuya T, Kim M, Lipinski M, Li J, Kim D, Lu T, Shen Y, Rameh L, Yankner B, Tsai L-H, et al. Negative regulation of Vps34 by Cdk mediated phosphorylation. Mol Cell 2010; 38:500-11; PMID:20513426; http://dx.doi.org/10. 1016/j.molcel.2010.05.009
68. Szyniarowski P, Corcelle-Termeau E, Farkas T, Høyer-Hansen M, Nylandsted J, Kallunki T, Jäättelä M. A comprehensive siRNA screen for kinases that suppress macroautophagy in optimal growth conditions. Autophagy 2011; 7:892-903; PMID:21508686; http://dx.doi.org/10.4161/auto.7.8. 15770
69. Matsumoto G, Wada K, Okuno M, Kurosawa M, Nukina N. Serine 403 phosphorylation of p62/SQSTM1 regulates selective autophagic clearance of ubiquitinated proteins. Mol Cell 2011; 44:279-89; PMID:22017874; http://dx.doi.org/10.1016/j.molcel.2011.07.039
70. Dagda RK, Zhu J, Kulich SM, Chu CT. Mitochondrially localized ERK2 regulates mitophagy and autophagic cell stress: implications for Parkinson's disease. Autophagy 2008; 4:770-82; PMID:18594198
71. Kabeya Y, Mizushima N, Ueno T, Yamamoto A, Kirisako T, Noda T, Kominami E, Ohsumi Y, Yoshimori T. LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing. EMBO J 2000; 19:5720-8; PMID:11060023; http://dx.doi.org/10.1093/emboj/19.21.5720
72. Rigbolt KT, Vanselow JT, Blagoev B. GProX, a user-friendly platform for bioinformatics analysis and visualization of quantitative proteomics data. Mol Cell Proteomics 2011; 10:007450; PMID:21602510; http://dx.doi.org/10.1074/mcp. O110.007450
73. Bennetzen MV, Cox J, Mann M, Andersen JS. PhosphoSiteAnalyzer: A Bioinformatic Platform for Deciphering Phospho Proteomes Using Kinase Predictions Retrieved from NetworKIN. J Proteome Res 2012; 11:3480-6; PMID:22471441; http://dx.doi.org/10.1021/pr300016e
74. Larkin MA, Blackshields G, Brown NP, Chenna R, McGettigan PA, McWilliam H, Valentin F, Wallace IM, Wilm A, Lopez R, et al. Clustal W and Clustal X version 2.0. Bioinformatics 2007; 23:2947-8; PMID:17846036; http://dx.doi.org/ 10.1093/bioinformatics/btm404
75. Letunic I, Bork P. Interactive Tree Of Life (iTOL): an online tool for phylogenetic tree display and annotation. Bioinformatics 2007; 23:127-8; PMID:17050570; http://dx.doi.org/10.1093/bioinformatics/btl529
76. Husmeier D. Sensitivity and specificity of inferring genetic regulatory interactions from microarray experiments with dynamic Bayesian networks. Bioinformatics 2003; 19:2271-82; PMID:14630656; http://dx.doi.org/10.1093/ bioinformatics/btg313