Impact of Next-Generation Technologies on Exploring Socioeconomically Important Parasites and Developing New Interventions

  • Cinzia Cantacessi
  • Andreas Hofmann
  • Bronwyn E. Campbell
  • Robin B. GasserEmail author
Part of the Methods in Molecular Biology book series (MIMB, volume 1247)


High-throughput molecular and computer technologies have become instrumental for systems biological explorations of pathogens, including parasites. For instance, investigations of the transcriptomes of different developmental stages of parasitic nematodes give insights into gene expression, regulation and function in a parasite, which is a significant step to understanding their biology, as well as interactions with their host(s) and disease. This chapter (1) gives a background on some key parasitic nematodes of socioeconomic importance, (2) describes sequencing and bioinformatic technologies for large-scale studies of the transcriptomes and genomes of these parasites, (3) provides some recent examples of applications and (4) emphasizes the prospects of fundamental biological explorations of parasites using these technologies for the development of new interventions to combat parasitic diseases.

Key words

Parasitic nematodes Genomics Transcriptomics Bioinformatics Next-generation sequencing Post-genomics Anthelmintic resistance Drug targets Diagnostic markers 



Funding from the Australian Research Council, the National Health and Medical Research Council, the Australian Academy of Science, the Alexander von Humboldt Foundation, and Melbourne Water Corporation is gratefully acknowledged (RBG). Our research program was also supported by the Victorian Life Sciences Computation Initiative (grant number VR0007) on its Peak Computing Facility at the University of Melbourne, an initiative of the Victorian Government (RBG).


  1. 1.
    de Silva NR, Brooker S, Hotez PJ et al (2003) Soil-transmitted helminth infections: updating the global picture. Trends Parasitol 19:547–551PubMedGoogle Scholar
  2. 2.
    Artis D (2006) New weapons in the war on worms: identification of putative mechanisms of immune-mediated expulsion of gastrointestinal nematodes. Int J Parasitol 36:723–733PubMedCentralPubMedGoogle Scholar
  3. 3.
    Bethony J, Brooker S, Albonico M et al (2006) Soil-transmitted helminth infections: ascariasis, trichuriasis, and hookworm. Lancet 367:1521–1532PubMedGoogle Scholar
  4. 4.
    Brooker S, Clements AC, Bundy DA (2006) Global epidemiology, ecology and control of soil-transmitted helminth infections. Adv Parasitol 62:221–261PubMedCentralPubMedGoogle Scholar
  5. 5.
    Nikolaou S, Gasser RB (2006) Prospects for exploring molecular developmental processes in Haemonchus contortus. Int J Parasitol 36:859–868PubMedGoogle Scholar
  6. 6.
    Hotez PJ, Fenwick A, Savioli L et al (2009) Rescuing the bottom billion through control of neglected tropical diseases. Lancet 373:1570–1575PubMedGoogle Scholar
  7. 7.
    O’Harhay MO, Horton J, Olliaro PL (2010) Epidemiology and control of human gastrointestinal parasites in children. Expert Rev Anti Infect Ther 8:219–234Google Scholar
  8. 8.
    Newton SE, Munn EA (1999) The development of vaccines against gastrointestinal nematode parasites, particularly Haemonchus contortus. Parasitol Today 15:116–122PubMedGoogle Scholar
  9. 9.
    Newton SE, Meeusen EN (2003) Progress and new technologies for developing vaccines against gastrointestinal nematode parasites of sheep. Parasite Immunol 25:283–296PubMedGoogle Scholar
  10. 10.
    Roeber F, Jex AR, Gasser RB (2013) Advances in the diagnosis of key gastrointestinal nematode infections of livestock, with an emphasis on small ruminants. Biotechnol Adv 31(8):1135–1152. doi: 10.1016/j.biotechadv.2013.01.008, pii: S0734-9750(13)00010-4PubMedGoogle Scholar
  11. 11.
    Wolstenholme AJ, Fairweather I, Prichard R et al (2004) Drug resistance in veterinary helminths. Trends Parasitol 20:469–476PubMedGoogle Scholar
  12. 12.
    Gilleard JS (2006) Understanding anthelmintic resistance: the need for genomics and genetics. Int J Parasitol 36:1227–1239PubMedGoogle Scholar
  13. 13.
    Wolstenholme AJ, Kaplan RM (2012) Resistance to macrocyclic lactones. Curr Pharm Biotechnol 13:873–887PubMedGoogle Scholar
  14. 14.
    Anderson RC (2000) Nematode parasites of vertebrate. Their development and transmission, 2nd edn. CABI Publishing, WallingfordGoogle Scholar
  15. 15.
    Kennedy MW, Harnett W (2001) Parasitic nematodes: molecular biology, biochemistry and immunology. CABI Publishing, New YorkGoogle Scholar
  16. 16.
    Nagaraj SH, Gasser RB, Ranganathan S (2007) A hitchhiker’s guide to expressed sequence tag (EST) analysis. Brief Bioinform 8:6–21PubMedGoogle Scholar
  17. 17.
    Parkinson J, Blaxter M (2009) Expressed sequence tags: an overview. Methods Mol Biol 533:1–12PubMedGoogle Scholar
  18. 18.
    Ranganathan S, Menon R, Gasser RB (2009) Advanced in silico analysis of expressed sequence tag (EST) data for parasitic nematodes of major socio-economic importance-fundamental insights toward biotechnological outcomes. Biotechnol Adv 27:439–448PubMedGoogle Scholar
  19. 19.
    Cantacessi C, Campbell BE, Gasser RB (2012) Key strongylid nematodes of animals – Impact of next-generation transcriptomics on systems biology and biotechnology. Biotechnol Adv 30:469–488PubMedGoogle Scholar
  20. 20.
    Hugot JP, Baujard P, Morand S (2001) Biodiversity in helminths and nematodes as a field of study: an overview. Nematology 3:199–208Google Scholar
  21. 21.
    Chitwood BG (1950) An outline classification of the Nematoda. In: Chitwood BG, Chitwood MB (eds) Introduction to nematology. University Park Press, Baltimore, MD, pp 12–25Google Scholar
  22. 22.
    Lichtenfels JR (1980) Keys to the genera of the Superfamily Strongyloidea. In: Anderson RC, Chabaud AG, Willmott S (eds) CIH Keys to the nematode parasites of vertebrate. CAB International, Wallingford, pp 1–41Google Scholar
  23. 23.
    Durette-Desset MC, Chabaud AG (1977) Essai de classification des nématodes Trichostrongyloidea. Ann Parasitol Hum Comp 52:539–558PubMedGoogle Scholar
  24. 24.
    Durette-Desset MC, Chabaud AG (1981) Nouvel essai de classification de nematode Trichostrongyloidea. Ann Parasitol Hum Comp 56:297–312PubMedGoogle Scholar
  25. 25.
    Durette-Desset MC (1983) Keys to the genera of the superfamily Trichostrongyloidea. In: Anderson RC, Chabaud AG, Willmott S (eds) CIH Keys to the nematode parasites of vertebrate. CAB International, Wallingford, pp 1–68Google Scholar
  26. 26.
    Skrjabin KI, Sobolev AA, Ivashkin VM (1967) Principles of Nematology. Izdatel’sto Akademii Nauk SSSR. Israel Program for Scientific Translations, WashingtonGoogle Scholar
  27. 27.
    Blaxter ML, De Ley P, Garey JR et al (1998) A molecular evolutionary framework for the phylum Nematoda. Nature 392:71–75PubMedGoogle Scholar
  28. 28.
    O’Connor LJ, Walkden-Brown SW, Kahn LP (2006) Ecology of the free-living stages of major trichostrongylid parasites of sheep. Vet Parasitol 142:1–15PubMedGoogle Scholar
  29. 29.
    Anderson N, Dash KM, Donald AD et al (1978) Epidemiology and control of nematode infections. In: Donald AD, Southcott WH, Dineen JK (eds) The epidemiology and control of gastrointestinal parasites of sheep in Australia. CSIRO, Australia, pp 23–51Google Scholar
  30. 30.
    Veglia F (1915) The anatomy and life-history of the Haemonchus contortus (Rud.). Rep Dir Vet Res 3–4:347–500Google Scholar
  31. 31.
    Monnig HO (1926) The life histories of Trichostrongylus instabilis and T. rugatus of sheep in South Africa. 11-12th Annual Report of the Director of Veterinary Education and Research, Union of South Africa, pp. 231–251Google Scholar
  32. 32.
    Olsen OW (1986) Animal parasites. Their life cycles and ecology. The quarterly review of biology. University of Chicago Press, Chicago, ILGoogle Scholar
  33. 33.
    Sommerville RI (1957) The exsheathing mechanism of nematode infective larva. Exp Parasitol 6:18–30PubMedGoogle Scholar
  34. 34.
    Rogers WP, Sommerville RI (1963) The infective stage of nematode parasites and its significance in parasitism. Adv Parasitol 1:109–177PubMedGoogle Scholar
  35. 35.
    Rogers WP, Sommerville RI (1968) The infectious process, and its relation to the development of early parasitic stages of nematodes. Adv Parasitol 6:327–348PubMedGoogle Scholar
  36. 36.
    Noble ER, Noble GA (1982) Parasitology: the biology of animal parasites, 5th edn. Lea & Febiger, Philadelphia, PAGoogle Scholar
  37. 37.
    Waller PJ (1997) Anthelmintic resistance. Vet Parasitol 72:391–412PubMedGoogle Scholar
  38. 38.
    Holmes PH (1985) Pathogenesis of trichostrongylosis. Vet Parasitol 18:89–101PubMedGoogle Scholar
  39. 39.
    Barker IK (1973) Scanning electron microscopy of duodenal mucosa of lambs infected with Trichostrongylus colubriformis. Parasitology 67:307–314PubMedGoogle Scholar
  40. 40.
    Barker IK (1975) Intestinal pathology associated with Trichostrongylus colubriformis infection in sheep – histology. Parasitology 70:165–171PubMedGoogle Scholar
  41. 41.
    Beveridge I, Pullman AL, Phillips PH et al (1989) Comparison on the effects of infection with Trichostrongylus colubriformis, Trichostrongylus vitrinus and Trichostrongylus rugatus in Merino lambs. Vet Parasitol 32:229–245PubMedGoogle Scholar
  42. 42.
    Garside P, Kennedy MW, Wakelin D et al (2000) Immunopathology of intestinal helminth infection. Parasite Immunol 22:605–612PubMedGoogle Scholar
  43. 43.
    Xu LQ, Yu SH, Jiang ZX et al (1995) Soil-transmitted helminthiases: nationwide survey in China. Bull World Health Organ 73:507–513PubMedCentralPubMedGoogle Scholar
  44. 44.
    Schneider B, Jariwala AR, Periago MV et al (2011) A history of hookworm vaccine development. Hum Vaccin 7:1234–1244PubMedCentralPubMedGoogle Scholar
  45. 45.
    Hotez PJ, Bethony J, Bottazzi ME et al (2006) New technologies for the control of human hookworm infection. Trends Parasitol 22:327–331PubMedGoogle Scholar
  46. 46.
    Schad GA, Warren KS (eds) (1990) Hookworm disease: current status and new directions. Taylor & Francis, LondonGoogle Scholar
  47. 47.
    Looss A (1898) Zur Lebensgeschichte des Ancylostoma duodenale. Eine Erwiederung an Herrn Prof Dr Leichtenstern. Zentralblatt fur Bakteriologie 24:442–449Google Scholar
  48. 48.
    Bruni A, Passalaqua A (1954) Sulla presenza di una mesomucinasi (jaluronidasi) in Ancylostoma duodenale. Boll Soc Ital Biol Sper 30:789–791PubMedGoogle Scholar
  49. 49.
    Lewert RM, Lee CL (1954) Studies on the passage of helminth larvae through host tissues. I Histochemical studies on extracellular changes caused by penetrating larvae II Enzymatic activity of larvae in vitro and in vivo. J Infect Dis 95:13–51PubMedGoogle Scholar
  50. 50.
    Gilman RH (1982) Hookworm disease: host-pathogen biology. Rev Infect Dis 4:824–829PubMedGoogle Scholar
  51. 51.
    Gasser RB, Cantacessi C, Loukas A (2008) DNA technological progress toward advanced diagnostic tools to support human hookworm control. Biotechnol Adv 26:35–45PubMedGoogle Scholar
  52. 52.
    Foster AO, Cross SX (1934) The direct development of hookworms after oral infection. Am J Trop Med 14:565–573Google Scholar
  53. 53.
    Schad GA, Chowdhury AB, Dean CG et al (1973) Arrested development in human hookworm infections: an adaptation to a seasonally unfavourable external environment. Science 180:500–501Google Scholar
  54. 54.
    Gibbs HC (1986) Hypobiosis in parasitic nematodes – an update. Adv Parasitol 25:129–174PubMedGoogle Scholar
  55. 55.
    Arasu P, Kwak D (1999) Developmental arrest and pregnancy-induced transmammary transmission of Ancylostoma caninum larvae in the murine model. J Parasitol 85:779–784PubMedGoogle Scholar
  56. 56.
    Hotez PJ, Brooker S, Bethony J et al (2004) Hookworm infection. N Engl J Med 351:799–807PubMedGoogle Scholar
  57. 57.
    Loukas A, Bethony J, Brooker S et al (2006) Hookworm vaccines: past, present, and future. Lancet Infect Dis 6:733–741PubMedGoogle Scholar
  58. 58.
    Gasbarre LC, Nansen P, Monrad J et al (1993) Serum anti-trichostrongyle antibody responses to first and second season grazing calves. Res Vet Sci 54:340–344PubMedGoogle Scholar
  59. 59.
    Klei TR (1997) Immunological control of gastrointestinal nematode infections. Vet Parasitol 72:507–523PubMedGoogle Scholar
  60. 60.
    Balic A, Bowles VM, Meeusen ELT (2000) The immunobiology of gastrointestinal nematode infections in ruminants. Adv Parasitol 45:181–241PubMedGoogle Scholar
  61. 61.
    Loukas A, Prociv P (2001) Immune responses in hookworm infection. Clin Microbiol Rev 14:689–703PubMedCentralPubMedGoogle Scholar
  62. 62.
    Loukas A, Constant SL, Bethony JM (2005) Immunobiology of hookworm infection. FEMS Immunol Med Microbiol 43:115–124PubMedGoogle Scholar
  63. 63.
    Gause WC, Urban JF Jr, Stadecker MJ (2003) The immune response to parasitic helminths: insights from murine models. Trends Immunol 24:269–277PubMedGoogle Scholar
  64. 64.
    Liu Z, Liu Q, Pesce J et al (2004) Requirements for the development of IL-4-producing T cells during intestinal nematode infections: what it takes to make a Th2 cell in vivo. Immunol Rev 201:57–74PubMedGoogle Scholar
  65. 65.
    Maizels RM, Yazdanbakhsh M (2003) Immune regulation by helminth parasites: cellular and molecular mechanisms. Nat Rev Immunol 3:733–744PubMedGoogle Scholar
  66. 66.
    Maizels RM, Balic A, Gomez-Escobar N et al (2004) Helminth parasites—masters of regulation. Immunol Rev 201:89–116PubMedGoogle Scholar
  67. 67.
    Anthony RM, Rutitzky LI, Urban JF Jr et al (2007) Protective immune mechanisms in helminth infection. Nat Rev Immunol 7:975–987PubMedCentralPubMedGoogle Scholar
  68. 68.
    Patel N, Kreider T, Urban JF Jr et al (2009) Characterization of effector mechanisms at the host: parasite interface during the immune response to tissue-dwelling intestinal nematode parasites. Int J Parasitol 39:13–21PubMedCentralPubMedGoogle Scholar
  69. 69.
    Liu Q, Kreider T, Bowdridge S et al (2010) B cells have distinct roles in host protection against different nematode parasites. J Immunol 184:5213–5223PubMedCentralPubMedGoogle Scholar
  70. 70.
    Allen JE, Maizels RM (2011) Diversity and dialogue in immunity to helminths. Nat Rev Immunol 11:375–388PubMedGoogle Scholar
  71. 71.
    White CJ, Maxwell CJ, Gallin JI (1986) Changes in the structural and functional properties of human eosinophils during experimental hookworm infection. J Infect Dis 154:778–783PubMedGoogle Scholar
  72. 72.
    Maxwell C, Hussain R, Nutman TB et al (1987) The clinical and immunological responses of normal human volunteers to low dose hookworm (Necator americanus) infection. Am J Trop Med Hyg 37:126–134PubMedGoogle Scholar
  73. 73.
    Miller JE, Horohov DW (2006) Immunological aspects of nematode parasite control in sheep. J Anim Sci 84:E124–E132PubMedGoogle Scholar
  74. 74.
    Larsen RH, Christensen CM, Lind P (1997) Serological assays for the identification of Oesophagostomum dentatum infections in pigs. Res Vet Sci 63:5–10PubMedGoogle Scholar
  75. 75.
    Joachim A, Ruttkowski B, Daugschies A (1998) Changes in antigen and glycoprotein patterns during the development of Oesophagostomum dentatum. Int J Parasitol 28:1853–1860PubMedGoogle Scholar
  76. 76.
    Joachim A, Ruttkowski B, Christensen CM et al (1999) Identification, isolation and characterisation of a species-specific 30 kDa-antigen of Oesophagostomum dentatum. Parasitol Res 85:307–311PubMedGoogle Scholar
  77. 77.
    Stockdale PH (1970) Necrotic enteritis of pigs caused by infection with Oesophagostomum spp. Br Vet J 126:526–530PubMedGoogle Scholar
  78. 78.
    Haussler M (1996) Immunhistologische Untersuchungen an der Dickdarmschleimhaut bei der Oesophagostomum dentatum-infektion des Schweines zu unterschiedlichen Zeitpunkten nach experimenteller infection. Dr Med. Vet. Thesis, Tierartzliche Hochschule, Hannover, GermanyGoogle Scholar
  79. 79.
    McSorley HJ, Loukas A (2010) The immunology of human hookworm infections. Parasite Immunol 32:549–559PubMedGoogle Scholar
  80. 80.
    Pearson MS, Tribolet L, Cantacessi C et al (2012) Molecular mechanisms of hookworm disease – stealth, virulence, and vaccines. J Allergy Clin Immunol 130:13–21PubMedGoogle Scholar
  81. 81.
    Holden-Dye L, Walker RJ (2007) Anthelmintic drugs. WormBook, ed. The C. elegans Research Community, doi:/10.1895/wormbook.1.143.1,
  82. 82.
    Robertson AP, Clark CL, Martin RJ (2010) Levamisole and ryanodine receptors. I: A contraction study in Ascaris suum. Mol Biochem Parasitol 171:1–7PubMedCentralPubMedGoogle Scholar
  83. 83.
    Keiser J, Utzinger J (2008) Efficacy of current drugs against soil-transmitted helminth infections: systematic review and meta-analysis. JAMA 299:1937–1948PubMedGoogle Scholar
  84. 84.
    Stepek G, Buttle DJ, Duce IR et al (2006) Human gastrointestinal nematode infections: are new control methods required? Int J Exp Pathol 87:325–341PubMedCentralPubMedGoogle Scholar
  85. 85.
    Epe C, Kaminsky R (2013) New advancement in anthelmintic drugs in veterinary medicine. Trends Parasitol 29:129–134PubMedGoogle Scholar
  86. 86.
    Gilleard JS, Beech RN (2007) Population genetics of anthelmintic resistance in parasitic nematodes. Parasitology 134:1133–1147PubMedGoogle Scholar
  87. 87.
    Kwa MS, Veenstra JG, Roos MH (1993) Molecular characterisation of beta-tubulin genes present in benzimidazole-resistant populations of Haemonchus contortus. Mol Biochem Parasitol 60:133–143PubMedGoogle Scholar
  88. 88.
    Geerts S, Coles GC, Gryssels B (1997) Anthelmintic resistance in human helminths: learning from problems with worm control in livestock. Parasitol Today 13:149–151PubMedGoogle Scholar
  89. 89.
    Roos MH (1997) The role of drugs in the control of parasitic nematode infections: must we do without? Parasitology 114:S137–S144PubMedGoogle Scholar
  90. 90.
    Geerts S, Gryssels B (2001) Anthelmintic resistance in human helminths: a review. Trop Med Int Health 6:915–921PubMedGoogle Scholar
  91. 91.
    Horton J (2003) Human gastrointestinal helminth infections: are they now neglected diseases? Trends Parasitol 19:527–531PubMedGoogle Scholar
  92. 92.
    Albonico M, Smith PG, Hall A et al (1994) A randomized controlled trial comparing mebendazole and albendazole against Ascaris, Trichuris and hookworm infections. Trans R Soc Trop Med Hyg 88:585–589PubMedGoogle Scholar
  93. 93.
    Albonico M, Bickle Q, Ramsan M et al (2003) Efficacy of mebendazole and levamisole alone or in combination against intestinal nematode infections after repeated targeted mebendazole treatment in Zanzibar. Bull World Health Org 81:343–352PubMedCentralPubMedGoogle Scholar
  94. 94.
    de Clercq D, Sacko M, Behnke J et al (1997) Failure of mebendazole in treatment of human hookworm infections in the southern region of Mali. Am J Trop Med Hyg 57:25–30PubMedGoogle Scholar
  95. 95.
    Reynoldson JA, Behnke JM, Gracey M et al (1997) Failure of pyrantel in treatment of human hookworm infections (Ancylostoma duodenale) in the Kimberley region of North West Australia. Acta Trop 68:301–312PubMedGoogle Scholar
  96. 96.
    Sacko M, de Clercq D, Behnke JM et al (1999) Comparison of the efficacy of mebendazole, albendazole and pyrantel in treatment of human hookworm infections in the southern region of Mali, West Africa. Trans R Soc Trop Med Hyg 93:195–203PubMedGoogle Scholar
  97. 97.
    Kotze AC, Kopp SR (2008) The potential impact of density dependent fecundity on the use of the faecal egg count reduction test for detecting drug resistance in human hookworms. PLoS Negl Trop Dis 2:e297PubMedCentralPubMedGoogle Scholar
  98. 98.
    Besier B (2007) New anthelmintics for livestock: the time is right. Trends Parasitol 23:21–24PubMedGoogle Scholar
  99. 99.
    Campbell BE, Hofmann A, McCluskey A et al (2010) Serine/threonine phosphatases in socioeconomically important parasitic nematodes—prospects as novel drug targets? Biotechnol Adv 29:28–39PubMedGoogle Scholar
  100. 100.
    Albonico M (2003) Methods to sustain drug efficacy in helminth control programmes. Acta Trop 86:233–242PubMedGoogle Scholar
  101. 101.
    Smits HL (2009) Prospects for the control of neglected tropical diseases by mass drug administration. Expert Rev Anti Infect Ther 7:37–56PubMedGoogle Scholar
  102. 102.
    Morgan ER, Coles GC (2010) Nematode control practices on sheep farms following an information campaign aiming to delay anthelmintic resistance. Vet Rec 166:301–303PubMedGoogle Scholar
  103. 103.
    Knox DP (2000) Development of vaccines against gastrointestinal nematodes. Parasitology 120:S43–S61PubMedGoogle Scholar
  104. 104.
    Dalton JP, Mulcahy G (2001) Parasite-vaccines—a reality? Vet Parasitol 98:149–167PubMedGoogle Scholar
  105. 105.
    Claerebout E, Knox DP, Vercruysse J (2003) Current research and future prospects in the development of vaccines against gastrointestinal nematodes in cattle. Expert Rev Vaccines 2:147–157PubMedGoogle Scholar
  106. 106.
    Bethony JM, Loukas A, Hotez PJ et al (2006) Vaccines against blood-feeding nematodes of humans and livestock. Parasitology 133:S63–S79PubMedGoogle Scholar
  107. 107.
    Diemert DJ, Bethony JM, Hotez PJ (2008) Hookworm vaccines. Clin Infect Dis 46:282–288PubMedGoogle Scholar
  108. 108.
    Hotez PJ, Bethony JM, Oliveira SC et al (2008) Multivalent anthelmintic vaccine to prevent hookworm and schistosomiasis. Expert Rev Vaccines 7:745–752PubMedGoogle Scholar
  109. 109.
    Jarrett WFH, Jennings FW, McIntyre WIM et al (1959) Studies on immunity to Haemonchus contortus infection—vaccination of sheep using a single dose of X-irradiated larvae. Am J Vet Res 20:527–531Google Scholar
  110. 110.
    Jarrett WFH, Jennings FW, McIntyre WIM et al (1961) Studies on immunity to Haemonchus contortus infection—double vaccination of sheep with irradiated larvae. Am J Vet Res 22:186–188PubMedGoogle Scholar
  111. 111.
    Miller TA (1971) Vaccination against the canine hookworm disease. Adv Parasitol 9:153–183PubMedGoogle Scholar
  112. 112.
    Smith WD, Angus KW (1980) Haemonchus contortus: attempts to immunize lambs with irradiated larvae. Res Vet Sci 29:45–50PubMedGoogle Scholar
  113. 113.
    Hotez PJ, Zhan B, Bethony JM et al (2003) Progress in the development of a recombinant vaccine for human hookworm disease: the Human Hookworm Vaccine Initiative. Int J Parasitol 33:1245–1258PubMedGoogle Scholar
  114. 114.
    Munn EA, Smith TS, Graham M et al (1993) Vaccination of merino lambs against haemonchosis with membrane-associated proteins from the adult parasite. Parasitology 106:63–66PubMedGoogle Scholar
  115. 115.
    Newton SE (1995) Progress on vaccination against Haemonchus contortus. Int J Parasitol 25:1281–1289PubMedGoogle Scholar
  116. 116.
    Newton SE, Morrish LE, Martin PJ et al (1995) Protection against multiply drug-resistant and geographically distant strains of Haemonchus contortus by vaccination with H11, a gut membrane-derived protective antigen. Int J Parasitol 25:511–521PubMedGoogle Scholar
  117. 117.
    Smith WD, van Wyk JA, van Strijp MF (2001) Preliminary observations on the potential of gut membrane proteins of Haemonchus contortus as candidate vaccine antigens in sheep on naturally infected pasture. Vet Parasitol 98:285–297PubMedGoogle Scholar
  118. 118.
    Knox DP, Smith WD (2001) Vaccination against gastrointestinal nematode parasites of ruminants using gut-expressed antigens. Vet Parasitol 100:21–32PubMedGoogle Scholar
  119. 119.
    Smith TS, Munn EA, Graham M et al (1993) Purification and evaluation of the integral membrane protein H11 as a protective antigen against Haemonchus contortus. Int J Parasitol 23:271–277PubMedGoogle Scholar
  120. 120.
    Smith WD, Smith SK, Murray JM (1994) Protection studies with integral membrane fractions of Haemonchus contortus. Parasitol Immunol 16:231–241Google Scholar
  121. 121.
    Cachat E, Newlands GF, Ekoja SE et al (2010) Attempts to immunize sheep against Haemonchus contortus using a cocktail of recombinant proteases derived from the protective antigen, H-gal-GP. Parasite Immunol 32:414–419PubMedGoogle Scholar
  122. 122.
    Pearson MS, Ranjit N, Loukas A (2010) Blunting the knife: development of vaccines targeting digestive proteases of blood-feeding helminth parasites. Biol Chem 391:901–911PubMedGoogle Scholar
  123. 123.
    Skuce PJ, Redmond DL, Liddell S et al (1999) Molecular cloning and characterization of gut-derived cysteine proteinases associated with a host protective extract from Haemonchus contortus. Parasitology 119:405–412PubMedGoogle Scholar
  124. 124.
    Williamson AL, Brindley PJ, Abbenante G et al (2003) Hookworm aspartic protease, Na-APR-2, cleaves human hemoglobin and serum proteins in a host-specific fashion. J Infect Dis 187:484–494PubMedGoogle Scholar
  125. 125.
    Smith WD, Newlands GF, Smith SK et al (2003) Metalloendopeptidases from the intestinal brush border of Haemonchus contortus as protective antigens for sheep. Parasite Immunol 25:313–323PubMedGoogle Scholar
  126. 126.
    Loukas A, Bethony JM, Williamson AL et al (2004) Vaccination of dogs with a recombinant cysteine protease from the intestine of canine hookworms diminishes the fecundity and growth of worms. J Infect Dis 189:1952–1961PubMedGoogle Scholar
  127. 127.
    Redmond DL, Knox DP (2004) Protection studies in sheep using affinity-purified and recombinant cysteine proteinases of adult Haemonchus contortus. Vaccine 22:4252–4261PubMedGoogle Scholar
  128. 128.
    Pearson MS, Bethony JM, Pickering DA et al (2009) An enzymatically inactivated hemoglobinase from Necator americanus induces neutralizing antibodies against multiple hookworm species and protects dogs against heterologous hookworm infection. FASEB J 23:3007–3019PubMedCentralPubMedGoogle Scholar
  129. 129.
    Knox DP, Smith SK, Redmond DL et al (2005) Protection induced by vaccinating sheep with a thiol-binding extract of Haemonchus contortus membranes is associated with its protease components. Parasite Immunol 27:121–126PubMedGoogle Scholar
  130. 130.
    Knox DP, Smith SK, Smith WD (1999) Immunization with an affinity purified protein extract from the adult parasite protects lambs against infection with Haemonchus contortus. Parasite Immunol 21:201–210PubMedGoogle Scholar
  131. 131.
    Loukas A, Bethony JM, Mendez S et al (2005) Vaccination with recombinant aspartic hemoglobinase reduced parasite load and blood loss after hookworm infection. PLoS Med 2:e295PubMedCentralPubMedGoogle Scholar
  132. 132.
    Xiao S, Zhan B, Xue J et al (2008) The evaluation of recombinant hookworm antigens as vaccine in hamsters (Mesocricetus auratus) challenged with human hookworm, Necator americanus. Exp Parasitol 118:32–40PubMedGoogle Scholar
  133. 133.
    Pearson MS, Pickering DA, Tribolet L et al (2010) Neutralizing antibodies to the hookworm hemoglobinase Na-APR-1: implications for a multivalent vaccine against hookworm infection and schistosomiasis. J Infect Dis 201:1561–1569PubMedGoogle Scholar
  134. 134.
    Hotez P, Haggerty J, Hawdon J et al (1990) Metalloproteases of infective Ancylostoma hookworm larvae and their possible functions in tissue invasion and ecdysis. Infect Immun 58:3883–3892PubMedCentralPubMedGoogle Scholar
  135. 135.
    Williamson AL, Lustigman S, Oksov Y et al (2006) Ancylostoma caninum MTP-1, an astacin-like metalloprotease secreted by infective hookworm larvae, is involved in tissue migration. Infect Immun 74:961–967PubMedCentralPubMedGoogle Scholar
  136. 136.
    Hawdon JM, Hotez PJ (1996) Hookworm: developmental biology of the infection process. Curr Opin Genet Dev 6:618–623PubMedGoogle Scholar
  137. 137.
    Hawdon JM, Jones BF, Hoffman DR et al (1996) Cloning and characterization of Ancylostoma-secreted protein. A novel protein associated with the transition to parasitism by infective hookworm larvae. J Biol Chem 22:6672–6678Google Scholar
  138. 138.
    Hawdon JM, Narasmihan S, Hotez PJ (1999) Ancylostoma secreted protein 2: cloning and characterization of a second member of a family of nematode secreted proteins from Ancylostoma caninum. Mol Biochem Parasitol 30:149–165Google Scholar
  139. 139.
    Cantacessi C, Campbell BE, Visser A et al (2009) A portrait of the “SCP/TAPS” proteins of eukaryotes – developing a framework for fundamental research and biotechnological outcomes. Biotechnol Adv 27:376–388PubMedGoogle Scholar
  140. 140.
    Brooker S, Bethony J, Hotez PJ (2004) Human hookworm infection in the 21st century. Adv Parasitol 58:197–288PubMedCentralPubMedGoogle Scholar
  141. 141.
    Diemert DJ, Pinto AG, Freire J et al (2012) Generalized urticaria induced by the Na-ASP-2 hookworm vaccine: implications for the development of vaccines against helminths. J Allergy Clin Immunol 130:169–176PubMedGoogle Scholar
  142. 142.
    Zhan B, Santiago H, Keegan B et al (2012) Fusion of Na-ASP-2 with human immunoglobulin Fcγ abrogates histamine release from basophils sensitized with anti-Na-ASP-2 IgE. Parasite Immunol 34:404–411PubMedGoogle Scholar
  143. 143.
    Alwine JC, Kemp DJ, Stark GR (1977) Method for detection of specific RNAs in agarose gels by transfer to diazobenzyloxymethyl-paper and hybridization with DNA probes. Proc Natl Acad Sci U S A 74:5350–5354PubMedCentralPubMedGoogle Scholar
  144. 144.
    Higuchi R, Fockler C, Dollinger G et al (1993) Kinetic PCR analysis: real-time monitoring of DNA amplification reactions. Biotechnology 11:1026–1030PubMedGoogle Scholar
  145. 145.
    Liang P, Pardee AB (1992) Differential display of eukaryotic messenger RNA by means of the polymerase chain reaction. Science 257:967–971PubMedGoogle Scholar
  146. 146.
    Pratt D, Cox GN, Milhausen MJ et al (1990) A developmentally regulated cysteine protease gene family in Haemonchus contortus. Mol Biochem Parasitol 43:181–191PubMedGoogle Scholar
  147. 147.
    Savin KW, Dopheide TA, Frenkel MJ et al (1990) Characterization, cloning and host-protective activity of a 30-kilodalton glycoprotein secreted by the parasitic stages of Trichostrongylus colubriformis. Mol Biochem Parasitol 41:167–176PubMedGoogle Scholar
  148. 148.
    Sangster NC, Bannan SC, Weiss AS et al (1999) Haemonchus contortus: sequence heterogeneity of internucleotide binding domains from P-glycoproteins. Exp Parasitol 91:250–257PubMedGoogle Scholar
  149. 149.
    Boag PR, Newton SE, Hansen NP et al (2000) Isolation and characterization of sex-specific transcripts from Oesophagostomum dentatum by RNA arbitrarily-primed PCR. Mol Biochem Parasitol 108:217–224PubMedGoogle Scholar
  150. 150.
    Moore J, Tetley L, Devaney E (2000) Identification of abundant mRNAs from the third stage larvae of the parasitic nematode, Ostertagia ostertagi. Biochem J 347:763–770PubMedCentralPubMedGoogle Scholar
  151. 151.
    Nikolaou S, Hartman D, Presidente PJ et al (2002) HcSTK, a Caenorhabditis elegans PAR-1 homologue from the parasitic nematode, Haemonchus contortus. Int J Parasitol 32:749–758PubMedGoogle Scholar
  152. 152.
    Hartman D, Cottee PA, Savin KW et al (2003) Haemonchus contortus: molecular characterisation of a small heat shock protein. Exp Parasitol 104:96–103PubMedGoogle Scholar
  153. 153.
    Cottee PA, Nisbet AJ, Abs El-Osta YG (2006) Construction of gender-enriched cDNA archives for adult Oesophagostomum dentatum by suppressive subtractive hybridization and a microarray analysis of expressed sequence tags. Parasitology 132:691–708PubMedGoogle Scholar
  154. 154.
    Velculescu VE, Zhang L, Vogelstein B et al (1995) Serial analysis of gene expression. Science 270:484–487PubMedGoogle Scholar
  155. 155.
    Velculescu VE, Zhang L, Zhou W et al (1997) Characterization of the yeast transcriptome. Cell 88:243–251PubMedGoogle Scholar
  156. 156.
    Boon K, Osorio EC, Greenhut SF et al (2002) An anatomy of normal and malignant gene expression. Proc Natl Acad Sci U S A 99:11287–11292PubMedCentralPubMedGoogle Scholar
  157. 157.
    Liang P (2002) SAGE Genie: a suite with panoramic view of gene expression. Proc Natl Acad Sci U S A 99:11547–11548PubMedCentralPubMedGoogle Scholar
  158. 158.
    Datson NA, van der Perk-de Jong J, van der Perk-de Jong MP et al (1999) MicroSAGE: a modified procedure for serial analysis of gene expression in limited amounts of tissue. Nucleic Acids Res 27:1300–1307PubMedCentralPubMedGoogle Scholar
  159. 159.
    Skuce PJ, Yaga R, Lainson FA et al (2005) An evaluation of serial analysis of gene expression (SAGE) in the parasitic nematode, Haemonchus contortus. Parasitology 130:553–559PubMedGoogle Scholar
  160. 160.
    Adams MD, Kelley JM, Gocayne JD et al (1991) Complementary DNA sequencing: expressed sequence tags and human genome project. Science 252:1651–1656PubMedGoogle Scholar
  161. 161.
    McCombie WR, Adams MD, Kelley JM et al (1992) Caenorhabditis elegans expressed sequence tags identify gene families and potential gene homologues. Nat Genet 1:124–131PubMedGoogle Scholar
  162. 162.
    Sanger F, Nicklen S, Coulson AR (1977) DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A 74:5463–5467PubMedCentralPubMedGoogle Scholar
  163. 163.
    Sanger F, Air GM, Barrell BG et al (1977) Nucleotide sequence of bacteriophage phi X174 DNA. Nature 265:687–695PubMedGoogle Scholar
  164. 164.
    Clifton SW, Mitreva M (2009) Strategies for undertaking expressed sequence tag (EST) projects. Methods Mol Biol 533:13–32PubMedGoogle Scholar
  165. 165.
    Blaxter ML, Raghavan N, Ghosh I et al (1996) Genes expressed in Brugia malayi infective third stage larvae. Mol Biochem Parasitol 77:77–96PubMedGoogle Scholar
  166. 166.
    Daub J, Loukas A, Pritchard DI et al (2000) A survey of genes expressed in adults of the human hookworm, Necator americanus. Parasitology 120:171–184PubMedGoogle Scholar
  167. 167.
    Hoekstra R, Visser A, Otsen M et al (2000) EST sequencing of the parasitic nematodes Haemonchus contortus suggests a shift in gene expression during transition to the parasitic stages. Mol Biochem Parasitol 110:53–68PubMedGoogle Scholar
  168. 168.
    McCarter JP, Abad J, Jones JT et al (2000) Rapid gene discovery in plant parasitic nematodes via gene discovery. Nematology 2:719–731Google Scholar
  169. 169.
    Williams SA, Lizotte-Waniewski MR, Foster J et al (2000) The filarial genome project: analysis of the nuclear, mitochondrial and endosymbiont genomes of Brugia malayi. Int J Parasitol 30:411–419PubMedGoogle Scholar
  170. 170.
    Parkinson J, Whitton C, Guiliano D et al (2001) 200,000 nematode ESTs on the net. Trends Parasitol 17:394–396PubMedGoogle Scholar
  171. 171.
    Parkinson J, Mitreva M, Whitton C et al (2004) A transcriptomic analysis of the phylum Nematoda. Nat Genet 36:1259–1267PubMedGoogle Scholar
  172. 172.
    Doyle MA, Gasser RB, Woodcroft BJ et al (2010) Drug target prediction and prioritization: using orthology to predict essentiality in parasite genomes. BMC Genomics 11:222PubMedCentralPubMedGoogle Scholar
  173. 173.
    Hartman D, Donald DR, Nikolaou S et al (2001) Analysis of developmentally regulated genes of the parasite Haemonchus contortus. Int J Parasitol 31:1236–1245PubMedGoogle Scholar
  174. 174.
    Campbell BE, Nagaraj SH, Hu M et al (2008) Gender-enriched transcripts in Haemonchus contortus—predicted functions and genetic interactions based on comparative analyses with Caenorhabditis elegans. Int J Parasitol 38:65–83PubMedGoogle Scholar
  175. 175.
    Ranjit N, Jones MK, Stenzel DJ et al (2006) A survey of the intestinal transcriptomes of the hookworms, Necator americanus and Ancylostoma caninum, using tissues isolated by laser-dissection microscopy. Int J Parasitol 36:701–710PubMedGoogle Scholar
  176. 176.
    Yin Y, Martin J, Abubucker S et al (2008) Intestinal transcriptomes of nematodes: comparison of the parasites Ascaris suum and Haemonchus contortus with the free-living Caenorhabditis elegans. PLoS Negl Trop Dis 2:e269PubMedCentralPubMedGoogle Scholar
  177. 177.
    Rabelo EM, Hall RS, Loukas A et al (2009) Improved insights into the transcriptome of the human hookworm Necator americanus- fundamental and biotechnological implications. Biotechnol Adv 27:122–132PubMedGoogle Scholar
  178. 178.
    DeRisi J, Penland L, Brown PO et al (1996) Use of a cDNA microarray to analyse gene expression patterns in human cancer. Nat Genet 14:457–460PubMedGoogle Scholar
  179. 179.
    Grant WN, Viney ME (2001) Post-genomic nematode parasitology. Int J Parasitol 31:879–888PubMedGoogle Scholar
  180. 180.
    Gasser RB, Cottee P, Nisbet AJ et al (2007) Oesophagostomum dentatum: potential as a model for genomic studies of strongylid nematodes, with biotechnological prospects. Biotechnol Adv 25:281–293PubMedGoogle Scholar
  181. 181.
    Nisbet AJ, Gasser RB (2004) Profiling of gender-specific gene expression for Trichostrongylus vitrinus (Nematoda: Strongylida) by microarray analysis of expressed sequence tag libraries constructed by suppressive-subtractive hybridization. Int J Parasitol 34:633–643PubMedGoogle Scholar
  182. 182.
    Moser JM, Freitas T, Arasu P et al (2005) Gene expression profiles associated with the transition to parasitism in Ancylostoma caninum larvae. Mol Biochem Parasitol 143:39–48PubMedGoogle Scholar
  183. 183.
    Datu BJ, Gasser RB, Nagaraj SH et al (2008) Transcriptional changes in the hookworm, Ancylostoma caninum, during the transition from a free-living to a parasitic larva. PLoS Negl Trop Dis 2:e130PubMedCentralPubMedGoogle Scholar
  184. 184.
    Nisbet AJ, Redmond DL, Matthews JB et al (2008) Stage-specific gene expression in Teladorsagia circumcincta (Nematoda: Strongylida) infective larvae and early parasitic stages. Int J Parasitol 38:829–838PubMedGoogle Scholar
  185. 185.
    Cantacessi C, Loukas A, Campbell BE et al (2009) Exploring transcriptional conservation between Ancylostoma caninum and Haemonchus contortus by oligonucleotide microarray and bioinformatic analyses. Mol Cell Probes 23:1–9PubMedGoogle Scholar
  186. 186.
    Yang GP, Kuang WW, Weigel RJ (1999) Combining SSH and cDNA microarrays for rapid identification of differentially expressed genes. Nucleic Acids Res 27:1517–1523PubMedCentralPubMedGoogle Scholar
  187. 187.
    Liu MY, Wang XL, Fu BQ et al (2007) Identification of stage-specifically expressed genes of Trichinella spiralis by suppression subtractive hybridization. Parasitology 134:1443–1455PubMedGoogle Scholar
  188. 188.
    Huang CQ, Gasser RB, Cantacessi C et al (2008) Genomic-bioinformatic analysis of transcripts enriched in the third-stage larva of the parasitic nematode Ascaris suum. PLoS Negl Trop Dis 2:e246PubMedCentralPubMedGoogle Scholar
  189. 189.
    Geldhof P, Whitton C, Gregory WF et al (2005) Characterisation of the two most abundant genes in the Haemonchus contortus expressed sequence tag dataset. Int J Parasitol 35:513–522PubMedGoogle Scholar
  190. 190.
    Mitreva M, McCarter JP, Arasu P et al (2005) Investigating hookworm genomes by comparative analysis of two Ancylostoma species. BMC Genomics 26:58Google Scholar
  191. 191.
    Abubucker S, Martin J, Yin Y et al (2008) The canine hookworm genome: analysis and classification of Ancylostoma caninum survey sequences. Mol Biochem Parasitol 157:187–192PubMedCentralPubMedGoogle Scholar
  192. 192.
    Wang Z, Abubucker S, Martin J et al (2010) Characterizing Ancylostoma caninum transcriptome and exploring nematode parasitic adaptation. BMC Genomics 11:307PubMedCentralPubMedGoogle Scholar
  193. 193.
    Margulies M, Egholm M, Altman WE et al (2005) Genome sequencing in microfabricated high-density picolitre reactors. Nature 437:376–380PubMedCentralPubMedGoogle Scholar
  194. 194.
    Bentley DR, Balasubramanian S, Swerdlow HP et al (2008) Accurate whole human genome sequencing using reversible terminator chemistry. Nature 456:53–59PubMedCentralPubMedGoogle Scholar
  195. 195.
    Harris TD, Buzby PR, Babcock H et al (2008) Single-molecule DNA sequencing of a viral genome. Science 320:106–109PubMedGoogle Scholar
  196. 196.
    Pandey V, Nutter RC, Prediger E (2008) Applied Biosystems SOLiD™ System: Ligation-Based Sequencing. In: Milton JM (ed) Next generation genome sequencing: towards personalized medicine. Wiley, Australia, pp 29–41Google Scholar
  197. 197.
    Mardis ER (2008) The impact of next-generation sequencing technology on genetics. Trends Genet 24:133–141PubMedGoogle Scholar
  198. 198.
    Wang Z, Gerstein M, Snyder M (2009) RNA-seq: a revolutionary tool for transcriptomics. Nat Rev Genet 10:57–63PubMedCentralPubMedGoogle Scholar
  199. 199.
    Marguerat S, Bahler J (2010) RNA-seq: from technology to biology. Cell Mol Life Sci 67:569–579PubMedCentralPubMedGoogle Scholar
  200. 200.
    Mardis ER (2008) Next-generation DNA sequencing methods. Ann Rev Genom Human Genet 9:387–402Google Scholar
  201. 201.
    Jex AR, Hu M, Littlewood DT et al (2008) Using 454 technology for long-PCR based sequencing of the complete mitochondrial genome from single Haemonchus contortus (Nematoda). BMC Genomics 9:11PubMedCentralPubMedGoogle Scholar
  202. 202.
    Jex AR, Li B, Young ND et al (2011) Ascaris suum draft genome. Nature 479:529–533PubMedGoogle Scholar
  203. 203.
    Cantacessi C, Mitreva M, Campbell BE et al (2010) First transcriptomic analysis of the economically important parasitic nematode, Trichostrongylus colubriformis, using a next-generation sequencing approach. Infect Genet Evol 10:1199–1207PubMedCentralPubMedGoogle Scholar
  204. 204.
    Cantacessi C, Campbell BE, Young ND et al (2010) Differences in transcription between free-living and CO2-activated third-stage larvae of Haemonchus contortus. BMC Genomics 11:266PubMedCentralPubMedGoogle Scholar
  205. 205.
    Cantacessi C, Mitreva M, Jex AR et al (2010) Massively parallel sequencing and analysis of the Necator americanus transcriptome. PLoS Negl Trop Dis 4:e684PubMedCentralPubMedGoogle Scholar
  206. 206.
    Cantacessi C, Jex AR, Hall RS et al (2010) A practical, bioinformatic workflow system for large data sets generated by next-generation sequencing. Nucleic Acids Res 38:e171PubMedCentralPubMedGoogle Scholar
  207. 207.
    Cantacessi C, Gasser RB, Strube C et al (2011) Deep insights into Dictyocaulus viviparus transcriptomes provides unique prospects for new drug targets and disease intervention. Biotechnol Adv 29:261–271PubMedGoogle Scholar
  208. 208.
    Young ND, Campbell BE, Hall RS et al (2010) Unlocking the transcriptomes of two carcinogenic parasites, Clonorchis sinensis and Opisthorchis viverrini. PLoS Negl Trop Dis 4:e719PubMedCentralPubMedGoogle Scholar
  209. 209.
    Young ND, Hall RS, Jex AR et al (2010) Elucidating the transcriptome of Fasciola hepatica—a key to fundamental and biotechnological discoveries for a neglected parasite. Biotechnol Adv 28:222–231PubMedGoogle Scholar
  210. 210.
    Young ND, Jex AR, Cantacessi C et al (2011) A portrait of the transcriptome of the neglected trematode, Fasciola gigantica – biological and biotechnological implications. PLoS Negl Trop Dis 5:e1004PubMedCentralPubMedGoogle Scholar
  211. 211.
    Young ND, Jex AR, Li B et al (2012) Whole-genome sequence of Schistosoma haematobium. Nat Genet 44:221–225PubMedGoogle Scholar
  212. 212.
    Huang X, Madan A (1999) CAP3: a DNA sequence assembly program. Genome Res 9:868–877PubMedCentralPubMedGoogle Scholar
  213. 213.
    Iseli C, Jongeneel CV, Bucher P (1999) ESTScan: a program for detecting, evaluating, and reconstructing potential coding regions in EST sequences. Proc Int Conf Intell Syst Mol Biol 1:138–148Google Scholar
  214. 214.
    Conesa A, Gotz S, Garcia-Gomez JM et al (2005) Blast2GO: a universal tool for annotation, visualization and analysis in functional genomics research. Bioinformatics 21:3674–3676PubMedGoogle Scholar
  215. 215.
    Nagaraj SH, Deshpande N, Gasser RB et al (2007) ESTExplorer: an expressed sequence tag (EST) assembly and annotation platform. Nucleic Acids Res 35:W135–W147Google Scholar
  216. 216.
    Hunter S, Apweiler R, Attwood TK et al (2009) InterPro: the integrative protein signature database. Nucleic Acids Res 37:D211–D215PubMedCentralPubMedGoogle Scholar
  217. 217.
    Soderlund C, Johnson E, Bomhoff M et al (2009) PAVE: program for assembling and viewing ESTs. BMC Genomics 10:400PubMedCentralPubMedGoogle Scholar
  218. 218.
    Nagasaki H, Michizuki T, Kodama Y et al (2013) DDJB Read Annotation Pipeline: a cloud computing-based pipeline for high-throughput analysis of next-generation sequencing data. DNA Res 20(4):383–390PubMedCentralPubMedGoogle Scholar
  219. 219.
    Falgueras J, Lara AJ, Fernandez-Poso N et al (2010) SeqTrim: a high throughput pipeline for pre-processing any type of sequence read. BMC Bioinformatics 11:38PubMedCentralPubMedGoogle Scholar
  220. 220.
    Myers EW (1995) Toward simplifying and accurately formulating fragment assembly. J Comput Biol 2:275–290PubMedGoogle Scholar
  221. 221.
    Idury RM, Waterman MS (1995) A new algorithm for DNA sequence assembly. J Comput Biol 2:291–306PubMedGoogle Scholar
  222. 222.
    Zerbino DR, Birney E (2008) Velvet: algorithms for de novo short read assembly using de Bruijn graphs. Genome Res 18:821–829PubMedCentralPubMedGoogle Scholar
  223. 223.
    Scheibye-Alsing K, Hoffmann S, Frankel A et al (2009) Sequence assembly. Comput Biol Chem 33:121–136PubMedGoogle Scholar
  224. 224.
    Miller JR, Koren S, Sutton G (2010) Assembly algorithms for next-generation sequencing data. Genomics 95:315–327PubMedCentralPubMedGoogle Scholar
  225. 225.
    Green P (1996) Documentation for PHRAP. Genome Center, University of Washington, Seattle,, USA
  226. 226.
    Sutton GG, White O, Adams MD et al (1995) TIGR assembler: a new tool for assembling large shotgun sequencing projects. Genome Sci Technol 1:9–19Google Scholar
  227. 227.
    Huang X, Wang J, Aluru S et al (2003) PCAP: a whole genome assembly program. Genome Res 13:2164–2170PubMedCentralPubMedGoogle Scholar
  228. 228.
    Chevreux B (2005) MIRA: an automated genome and EST assembler. Ph.D Thesis, German Cancer Research Center Heidelberg, Duisburg, GermanyGoogle Scholar
  229. 229.
    Warren RL, Sutton GC, Jones SJM et al (2007) Assembling millions of short DNA sequences using SSAKE. Bioinformatics 23:500–501PubMedGoogle Scholar
  230. 230.
    Schulz MH, Zerbino DR, Vingron M et al (2012) Oases: robust de novo RNA-seq assembly across the dynamic range of expression levels. Bioinformatics 28:1086–1092PubMedCentralPubMedGoogle Scholar
  231. 231.
    Hernandez D, François P, Farinelli L et al (2008) De novo bacterial genome sequencing: millions of very short reads assembled on a desktop computer. Genome Res 18:802–809PubMedCentralPubMedGoogle Scholar
  232. 232.
    Pevzner PA, Tang H, Waterman MS (2001) An Eulerian path approach to DNA fragment assembly. Proc Natl Acad Sci U S A 98:9748–9753PubMedCentralPubMedGoogle Scholar
  233. 233.
    Simpson JT, Wong K, Jackman SD et al (2009) ABySS: a parallel assembler for short read sequence data. Genome Res 19:1117–1123PubMedCentralPubMedGoogle Scholar
  234. 234.
    Li R, Li Y, Kristiansen K et al (2008) SOAP: short oligonucleotide alignment program. Bioinformatics 24:713–714PubMedGoogle Scholar
  235. 235.
    Grabherr MG, Haas BJ, Yassour M et al (2011) Full-length transcriptome assembly from RNA-Seq data without a reference genome. Nat Biotechnol 29:644–652PubMedCentralPubMedGoogle Scholar
  236. 236.
    Min XJ, Butler G, Storms R et al (2005) OrfPredictor: predicting protein-coding regions in EST-derived sequences. Nucleic Acids Res 33:W677–W680PubMedCentralPubMedGoogle Scholar
  237. 237.
    Fukunishi Y, Hayashizaki Y (2001) Amino acid translation program for full-length cDNA sequences with frameshift errors. Physiol Genomics 5:81–87PubMedGoogle Scholar
  238. 238.
    Klassen JL, Currie CR (2013) ORFcor: identifying and accommodating ORF prediction inconsistencies for phylogenetic analysis. PLoS One 8:e58387PubMedCentralPubMedGoogle Scholar
  239. 239.
    Hofmann K, Bucher P, Falquet L et al (1999) The Prosite Database, its status in 1999. Nucleic Acids Res 27:215–219PubMedCentralPubMedGoogle Scholar
  240. 240.
    Attwood TK, Croning MD, Flower DR et al (2000) Prints-S: the database formerly known as prints. Nucleic Acids Res 28:225–227PubMedCentralPubMedGoogle Scholar
  241. 241.
    Bateman A, Birney E, Durbin R et al (2000) The Pfam protein families database. Nucleic Acids Res 28:263–266PubMedCentralPubMedGoogle Scholar
  242. 242.
    Corpet F, Gouzy J, Kahn D (1999) Recent improvements of the ProDom database of protein domain families. Nucleic Acids Res 27:263–267PubMedCentralPubMedGoogle Scholar
  243. 243.
    Schultz J, Copley RR, Doerks T et al (2000) Smart: a web-based tool for the study of genetically mobile domains. Nucleic Acids Res 28:231–234PubMedCentralPubMedGoogle Scholar
  244. 244.
    Ashburner M, Ball CA, Blake JA et al (2000) Gene ontology: tool for the unification of biology. The gene ontology consortium. Nat Genet 25:25–29PubMedCentralPubMedGoogle Scholar
  245. 245.
    Krogh A, Larsson B, von Heijne G et al (2001) Predicting transmembrane protein topology with a hidden Markov model: application to complete genomes. J Mol Biol 305:567–580PubMedGoogle Scholar
  246. 246.
    Nielsen H, Engelbrecht J, Brunak S et al (1997) A neural network method for the identification of prokaryotic and eukaryotic signal peptides and prediction of their cleavage sites. Int J Neural Syst 8:581–599PubMedGoogle Scholar
  247. 247.
    Altschul SF, Gish W, Miller W et al (1990) Basic local alignment search tool. J Mol Biol 215:403–410PubMedGoogle Scholar
  248. 248.
    Benson DA, Karsch-Mizrachi I, Lipman DJ et al (2002) GenBank. Nucleic Acids Res 30:17–20PubMedCentralPubMedGoogle Scholar
  249. 249.
    Stoesser G, Baker W, van den Broek A et al (2002) The EMBL nucleotide sequence database. Nucleic Acids Res 30:21–26PubMedCentralPubMedGoogle Scholar
  250. 250.
    Tateno Y, Imanishi S, Miyazaki S et al (2002) DNA Data Bank of Japan (DDBJ) for genome scale research in life sciences. Nucleic Acids Res 30:27–30PubMedCentralPubMedGoogle Scholar
  251. 251.
    Wheeler DL, Church DM, Lash AE et al (2001) Database resources of the national center for biotechnology information. Nucleic Acids Res 29:11–16PubMedCentralPubMedGoogle Scholar
  252. 252.
    Shumway M, Cochrane G, Sugawara H (2010) Archiving next generation sequencing data. Nucleic Acids Res 38:D870–D871PubMedCentralPubMedGoogle Scholar
  253. 253.
    Berman HM, Westbrook J, Feng Z et al (2000) The protein data bank. Nucleic Acids Res 28:235–242PubMedCentralPubMedGoogle Scholar
  254. 254.
    Bairoch A, Apweiler R (2000) The SWISS-PROT protein sequence database and its supplement TrEMBL in 2000. Nucleic Acids Res 28:45–48PubMedCentralPubMedGoogle Scholar
  255. 255.
    Bairoch A, Apweiler R (1996) The SWISS-PROT protein sequence data bank and its new supplement TREMBL. Nucleic Acids Res 24:21–25PubMedCentralPubMedGoogle Scholar
  256. 256.
    Cherry JM, Ball C, Weng S et al (1997) Genetic and physical maps of Saccharomyces cerevisiae. Nature 387:67–73PubMedCentralPubMedGoogle Scholar
  257. 257.
    Tweedie S, Ashburner M, Falls K et al (2009) FlyBase: enhancing Drosophila Gene Ontology annotations. Nucleic Acids Res 37:D555–D559PubMedCentralPubMedGoogle Scholar
  258. 258.
    Bult CJ, Epping JT, Kadin JA et al (2008) The Mouse Genome Database (MGD): mouse biology and model systems. Nucleic Acids Res 36:D724–D728PubMedCentralPubMedGoogle Scholar
  259. 259.
    Harris TW, Antoshechkin I, Bieri T et al (2010) WormBase: a comprehensive resource for nematode research. Nucleic Acids Res 38:D463–D467PubMedCentralPubMedGoogle Scholar
  260. 260.
    Bieri T, Blasiar D, Ozersky P et al (2006) WormBase: new content and better access. Nucleic Acids Res 35:D506–D510PubMedCentralPubMedGoogle Scholar
  261. 261.
    Schwarz EM, Antoshechkin I, Bastiani C et al (2006) WormBase: better software, richer content. Nucleic Acids Res 34:D475–D478PubMedCentralPubMedGoogle Scholar
  262. 262.
    Yook K, Harris TW, Bieri T et al (2012) WormBase 2012: more genomes, more data, new website. Nucleic Acids Res 40:D735–D741PubMedCentralPubMedGoogle Scholar
  263. 263.
    Mangiola S, Young ND, Korhonen P et al (2013) Getting the most out of parasitic helminth transcriptomes using HelmDB: implications for biology and biotechnology. Biotechnol Adv 31(8):1109–1119. doi: 10.1016/j.biotechadv.2012.12.004, pii: S0734-9750(12)00197-8PubMedGoogle Scholar
  264. 264.
    Brenner S (1974) The genetics of Caenorhabditis elegans. Genetics 77:71–94PubMedCentralPubMedGoogle Scholar
  265. 265.
    The C. elegans Sequencing Consortium (1998) Genome sequence of the nematode C. elegans: a platform for investigating biology. Science 282:2012–2018Google Scholar
  266. 266.
    Fire A, Xu S, Montgomery MK et al (1998) Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature 391:806–811PubMedGoogle Scholar
  267. 267.
    Barstead R (2001) Genome-wide RNAi. Curr Opin Chem Biol 5:63–66PubMedGoogle Scholar
  268. 268.
    Kamath RS, Ahringer J (2003) Genome-wide RNAi screening in Caenorhabditis elegans. Methods 30:313–321PubMedGoogle Scholar
  269. 269.
    Simmer F, Moorman C, van der Linden AM et al (2003) Genome-wide RNAi of C. elegans using the hypersensitive rrf-3 strain reveals novel gene functions. PLoS Biol 1:E12PubMedCentralPubMedGoogle Scholar
  270. 270.
    Sugimoto A (2004) High-throughput RNAi in Caenorhabditis elegans: genome-wide screens and functional genomics. Differentiation 72:81–91PubMedGoogle Scholar
  271. 271.
    Sonnichsen B, Koski LB, Walsh A et al (2005) Full-genome RNAi profiling of early embryogenesis in Caenorhabditis elegans. Nature 434:462–469PubMedGoogle Scholar
  272. 272.
    Tabara H, Grishok A, Mello CC (1998) RNAi in C. elegans: soaking in the genome sequence. Science 282:430–431PubMedGoogle Scholar
  273. 273.
    Timmons L, Fire A (1998) Specific interference by ingested dsRNA. Nature 395:854PubMedGoogle Scholar
  274. 274.
    Tabara H, Sarkissian M, Kelly WG et al (1999) The rde-1 gene, RNA interference, and transposon silencing in C. elegans. Cell 99:123–132PubMedGoogle Scholar
  275. 275.
    Tavernarakis N, Wang SL, Dorovkov M et al (2000) Heritable and inducible genetic interference by double-stranded RNA encoded by transgenes. Nat Genet 24:180–183PubMedGoogle Scholar
  276. 276.
    Maeda I, Kohara Y, Yamamoto M et al (2001) Large-scale analysis of gene function in Caenorhabditis elegans by high-throughput RNAi. Curr Biol 11:171–176PubMedGoogle Scholar
  277. 277.
    Ashrafi K, Chang FY, Watts JL et al (2003) Genome-wide RNAi analysis of Caenorhabditis elegans fat regulatory genes. Nature 421:268–272PubMedGoogle Scholar
  278. 278.
    Britton C, Murray L (2006) Using Caenorhabditis elegans for functional analysis of genes of parasitic nematodes. Int J Parasitol 36:651–659PubMedGoogle Scholar
  279. 279.
    Geldhof P, Visser A, Clark D et al (2007) RNA interference in parasitic helminths: current situation, potential pitfalls and future prospects. Parasitology 134:609–619PubMedGoogle Scholar
  280. 280.
    Morris KV (2008) RNA-mediated transcriptional gene silencing in human cells. Curr Top Microbiol Immunol 320:211–224PubMedGoogle Scholar
  281. 281.
    Rosso MN, Jones JT, Abad P (2009) RNAi and functional genomics in plant parasitic nematodes. Annu Rev Phytopathol 47:207–232PubMedGoogle Scholar
  282. 282.
    Serkirk ME, Huang SC, Knox DP et al (2012) The development of RNA interference (RNAi) in gastrointestinal nematodes. Parasitology 139:605–612Google Scholar
  283. 283.
    Stinchcomb DT, Shaw JE, Carr SH et al (1985) Extrachromosomal DNA transformation of Caenorhabditis elegans. Mol Cell Biol 5:3484–3496PubMedCentralPubMedGoogle Scholar
  284. 284.
    Fire A (1986) Integrative transformation of Caenorhabditis elegans. EMBO J 5:2673–2680PubMedCentralPubMedGoogle Scholar
  285. 285.
    Chalfie M, Tu Y, Euskirchen G et al (1994) Green fluorescent protein as a marker for gene expression. Science 263:802–805PubMedGoogle Scholar
  286. 286.
    Lok JB, Artis D (2008) Transgenesis and neuronal ablation in parasitic nematodes: revolutionary new tools to dissect host-parasite interactions. Parasite Immunol 30:203–214PubMedCentralPubMedGoogle Scholar
  287. 287.
    Hobert O, Loria P (2006) Uses of GFP in Caenorhabditis elegans. Methods Biochem Anal 47:203–226PubMedGoogle Scholar
  288. 288.
    Reinke V, Smith HE, Nance J et al (2000) A global profile of germline gene expression in C. elegans. Mol Cell 6:605–616PubMedGoogle Scholar
  289. 289.
    Kim SK, Lund J, Kiraly M et al (2001) A gene expression map for Caenorhabditis elegans. Science 293:2087–2092PubMedGoogle Scholar
  290. 290.
    Jiang M, Ryu J, Kiraly M et al (2001) Genome-wide analysis of developmental and sex-regulated gene expression profiles in Caenorhabditis elegans. Proc Natl Acad Sci U S A 98:218–223PubMedCentralPubMedGoogle Scholar
  291. 291.
    Chilton NB (2004) The use of nuclear ribosomal DNA markers for the identification of bursate nematodes (order Strongylida) and for the diagnosis of infections. Anim Health Res Rev 5:173–187PubMedGoogle Scholar
  292. 292.
    Bürglin TR, Lobos E, Blaxter ML (1998) Caenorhabditis elegans as a model for parasitic nematodes. Int J Parasitol 28:395–411PubMedGoogle Scholar
  293. 293.
    Mitreva M, Jasmer JP, Zarlenga DS et al (2011) The draft genome of the parasitic nematode Trichinella spiralis. Nat Genet 43:228–243PubMedCentralPubMedGoogle Scholar
  294. 294.
    Williamson AL, Lecchi P, Turk BE et al (2004) A multi-enzyme cascade of hemoglobin proteolysis in the intestine of blood-feeding hookworms. J Biol Chem 279:35950–35957PubMedGoogle Scholar
  295. 295.
    Ranjit N, Zhan B, Hamilton B et al (2009) Proteolytic degradation of hemoglobin in the intestine of the human hookworm Necator americanus. J Infect Dis 199:904–912PubMedGoogle Scholar
  296. 296.
    Furmidge BA, Horn LA, Pritchard DI (1996) The anti-haemostatic strategies of the human hookworm Necator americanus. Parasitology 112:81–87PubMedGoogle Scholar
  297. 297.
    Milstone AM, Harrison LM, Bungiro RD et al (2000) A broad spectrum kunitz type serine protease inhibitor secreted by the hookworm Ancylostoma ceylanicum. J Biol Chem 275:29391–29399PubMedGoogle Scholar
  298. 298.
    Grad LI, Sayles LC, Lemire BD (2007) Isolation and functional analysis of mitochondria from the nematode Caenorhabditis elegans. Methods Mol Biol 372:51–66PubMedGoogle Scholar
  299. 299.
    Fetterer RH (1996) Growth and cuticular synthesis in Ascaris suum larvae during development from third to fourth stage in vitro. Vet Parasitol 65:275–282PubMedGoogle Scholar
  300. 300.
    Quinn CC, Pfeil DS, Wadsworth WG (2008) CED-10/Rac1 mediates axon guidance by regulating the asymmetric distribution of MIG-10/lamellipodin. Curr Biol 18:808–813PubMedCentralPubMedGoogle Scholar
  301. 301.
    Ranjit N, Zhan B, Stenzel DJ et al (2008) A family of cathepsin B cysteine proteases expressed in the gut of the human hookworm, Necator americanus. Mol Biochem Parasitol 160:90–99PubMedGoogle Scholar
  302. 302.
    Robinson BW, Venaille TJ, Mendis AH et al (1990) Allergens as proteases: an Aspergillus fumigatus proteinase directly induces human epithelial cell detachment. J Allergy Clin Immunol 86:726–731PubMedGoogle Scholar
  303. 303.
    Björnberg F, Lantz M, Gullberg U (1995) Metalloproteases and serineproteases are involved in the cleavage of the two tumour necrosis factor (TNF) receptors to soluble forms in the myeloid cell lines U-937 and THP-1. Scand J Immunol 42:418–424PubMedGoogle Scholar
  304. 304.
    Hotez PJ, Prichard DI (1995) Hookworm infection. Sci Am 6:42–48Google Scholar
  305. 305.
    Shaw RJ, McNeill MM, Maass DR et al (2003) Identification and characterisation of an aspartyl protease inhibitor homologue as a major allergen of Trichostrongylus colubriformis. Int J Parasitol 33:1233–1243PubMedGoogle Scholar
  306. 306.
    Williamson AL, Brindley PJ, Knox DP et al (2003) Digestive proteases of blood-feeding nematodes. Trends Parasitol 19:417–423PubMedGoogle Scholar
  307. 307.
    Cottee PA, Nisbet AJ, Boag PR et al (2004) Characterization of major sperm protein genes and their expression in Oesophagostomum dentatum (Nematoda; Strongylida). Parasitology 129:479–490PubMedGoogle Scholar
  308. 308.
    Miller MA, Nguyen VQ, Lee MH et al (2001) A sperm cytoskeletal protein that signals oocyte meiotic maturation and ovulation. Science 291:2144–2147, Erratum in: Science 292, 639PubMedGoogle Scholar
  309. 309.
    Miller MA, Ruest PJ, Kosinski M et al (2003) An Eph receptor sperm-sensing control mechanism for oocyte meiotic maturation in Caenorhabditis elegans. Genes Dev 17:187–200PubMedCentralPubMedGoogle Scholar
  310. 310.
    Freigofas R, Leibold W, Daugschies A et al (2001) Products of fourth-stage larvae of Oesophagostomum dentatum induce proliferation in naïve porcine mononuclear cells. J Vet Med B Infect Dis Vet Public Health 48:603–611PubMedGoogle Scholar
  311. 311.
    Campbell BE, Tarleton M, Gordon CP et al (2011) Norcantharidin analogues with nematocidal activity in Haemonchus contortus. Bioorg Med Chem Lett 21:3277–3281PubMedGoogle Scholar
  312. 312.
    McCluskey A, Keane MA, Walkom CC et al (2002) The first two cantharidin analogues displaying PP1 selectivity. Bioorg Med Chem Lett 12:391–393PubMedGoogle Scholar
  313. 313.
    Hill TA, Stewart SG, Sauer B et al (2007) Heterocyclic substituted cantharidin and norcantharidin analogues—synthesis, protein phosphatase (1 and 2A) inhibition, and anti-cancer activity. Bioorg Med Chem Lett 17:3392–3397PubMedGoogle Scholar
  314. 314.
    Stewart SG, Hill TA, Gilbert J et al (2007) Synthesis and biological evaluation of norcantharidin analogues: towards PP1 selectivity. Bioorg Med Chem 15:7301–7310PubMedGoogle Scholar
  315. 315.
    Olson SK, Bishop JR, Yates JR et al (2006) Identification of novel chondroitin proteoglycans in Caenorhabditis elegans: embryonic cell division depends on CPG-1 and CPG-2. J Cell Biol 173:985–994PubMedCentralPubMedGoogle Scholar
  316. 316.
    Zhan B, Liu Y, Badamchian M et al (2003) Molecular characterisation of the Ancylostoma-secreted protein family from the adult stage of Ancylostoma caninum. Int J Parasitol 33:897–907PubMedGoogle Scholar
  317. 317.
    Mulvenna J, Hamilton B, Nagaraj S et al (2009) Proteomic analysis of the excretory/secretory component of the blood-feeding stage of the hookworm, Ancylostoma caninum. Mol Cell Proteomics 8:109–121PubMedGoogle Scholar
  318. 318.
    Bethony J, Loukas A, Smout M et al (2005) Antibodies against a secreted protein from hookworm larvae reduce the intensity of hookworm infection in humans and vaccinated laboratory animals. FASEB J 19:1743–1745PubMedGoogle Scholar
  319. 319.
    Bethony JM, Simon G, Diemert DJ et al (2008) Randomized, placebo-controlled, double-blind trial of the Na-ASP-2 hookworm vaccine in unexposed adults. Vaccine 26:2408–2417PubMedGoogle Scholar
  320. 320.
    Mendez S, Samuel A D’, Antoine AD et al (2008) Use of the air pouch model to investigate immune responses to a hookworm vaccine containing the Na-ASP-2 protein in rats. Parasite Immunol 30:53–56PubMedGoogle Scholar
  321. 321.
    Osman A, Wang CK, Winter A et al (2012) Hookworm SCP/TAPS protein structure - a key to understanding host-parasite interactions and developing new interventions. Biotechnol Adv 30:652–657PubMedGoogle Scholar
  322. 322.
    Hopkins AL, Groom CR (2002) The druggable genome. Nature 1:727–730Google Scholar
  323. 323.
    Chang A, Scheer M, Grote A et al (2009) BRENDA, AMENDA and FRENDA the enzyme information system: new content and tools in 2009. Nucleic Acids Res 37:D588–D592PubMedCentralPubMedGoogle Scholar
  324. 324.
    Manning G, Whyte DB, Martinez R et al (2002) The protein kinase complement of the human genome. Science 298:1912–1934PubMedGoogle Scholar
  325. 325.
    Manning G, Reiner DS, Lauwaet T et al (2011) The minimal kinome of Giardia lamblia illuminates early kinase evolution and unique parasite biology. Genome Biol 12:R66PubMedCentralPubMedGoogle Scholar
  326. 326.
    Lucet IS, Tobin A, Drewry D et al (2012) Plasmodium kinases as targets for new-generation antimalarials. Future Med Chem 4:2295–2310PubMedGoogle Scholar
  327. 327.
    Liotta F, Siekierka JJ (2010) Apicomplexa, trypanosoma and parasitic nematode protein kinases as antiparasitic therapeutic targets. Curr Opin Invest Drugs 11:147–156Google Scholar
  328. 328.
    Knobloch J, Kunz W, Grevelding CG (2006) Herbimycin A suppresses mitotic activity and egg production of female Schistosoma mansoni. Int J Parasitol 36:1261–1272PubMedGoogle Scholar
  329. 329.
    Campbell BE, Boag PR, Hofmann A et al (2011) Atypical (RIO) protein kinases from Haemonchus contortus – Promise as new targets for nematocidal drugs. Biotechnol Adv 29:338–350PubMedGoogle Scholar
  330. 330.
    Hu M, Laronde-Leblanc N, Sternberg PW et al (2008) Tv-RIO1 – an atypical protein kinase from the parasitic nematode Trichostrongylus vitrinus. Parasit Vectors 1:34PubMedCentralPubMedGoogle Scholar
  331. 331.
    Ferreira CV, Gusto GZ, Sousa AC et al (2006) Natural compounds as source of protein phosphatase inhibitors: application to the rational design of small-molecule derivatives. Biochemie 88:1859–1873Google Scholar
  332. 332.
    Cho YY, Yao K, Kim HG et al (2007) Ribosomal S6 kinase 2 is a key regulator in tumor promoter induced cell transformation. Cancer Res 67:8104–8112PubMedCentralPubMedGoogle Scholar
  333. 333.
    Nöthlings U, Murphy SP, Wilkens LR et al (2007) Flavonoids and pancreatic cancer risk. Am J Epidemiol 166:924–931PubMedGoogle Scholar
  334. 334.
    Meyer M, Briggs AW, Maricic T et al (2007) From micrograms to picograms: quantitative PCR reduces the material demands in high throughput sequencing. Nucleic Acids Res 1:1–6Google Scholar
  335. 335.
    Jarvie T, Harkins T (2008) Transcriptome sequencing with the Genome Sequencer FLX system. Nat Methods 5:6–8Google Scholar
  336. 336.
    Flicek B, Birney E (2009) Sense from sequence reads, methods for alignment and assembly. Nat Methods 6:S6–S12PubMedGoogle Scholar
  337. 337.
    Pepke S, Wold B, Mortazavi A (2009) Computational approaches to the analysis of ChIP-seq and RNA-seq data. Nat Methods 6:S22–S32PubMedCentralPubMedGoogle Scholar
  338. 338.
    Reinhardt JA, Baltrus DA, Nishimura MT et al (2009) De novo assembly using low-coverage short read sequence data from the rice pathogen Pseudomonas syringae pv. oryzae. Genome Res 19:294–305PubMedCentralPubMedGoogle Scholar
  339. 339.
    Nagarajan H, Butler JE, Klimes A et al (2010) De novo assembly of the complete genome of an enhanced electricity-producing variant of Geobacter sulfurreducens using only short reads. PLoS One 5:e10922PubMedCentralPubMedGoogle Scholar
  340. 340.
    Tsai IJ, Otto TD, Berriman M (2010) Improving draft assemblies by iterative mapping and assembly of short reads to eliminate gaps. Genome Biol 11:R41PubMedCentralPubMedGoogle Scholar
  341. 341.
    Gregory SG, Barlow KF, McLay KE et al (2006) The DNA sequence and biological annotation of human chromosome 1. Nature 441:315–321PubMedGoogle Scholar
  342. 342.
    Karp PD (1998) What we do not know about sequence analysis and sequence databases. Bioinformatics 14:753–754PubMedGoogle Scholar
  343. 343.
    Benitez-Paez A (2009) Considerations to improve functional annotations in biological databases. OMICS 13:527–535PubMedGoogle Scholar
  344. 344.
    Boag PR, Ren P, Newton SE et al (2003) Molecular characterisation of a male-specific serine/threonine phosphatase from Oesophagostomum dentatum (Nematoda: Strongylida), and functional analysis of homologues in Caenorhabditis elegans. Int J Parasitol 33:313–325PubMedGoogle Scholar
  345. 345.
    Issa Z, Grant WN, Stasiuk S et al (2005) Development of methods for RNA interference in the sheep gastrointestinal parasite, Trichostrongylus colubriformis. Int J Parasitol 35:935–940PubMedGoogle Scholar
  346. 346.
    Geldhof P, Murray L, Couthier A et al (2006) Testing the efficacy of RNA interference in Haemonchus contortus. Int J Parasitol 36:801–810PubMedGoogle Scholar
  347. 347.
    Kotze AC, Bagnall NH (2006) RNA interference in Haemonchus contortus: suppression of beta-tubulin gene expression in L3, L4 and adult worms in vitro. Mol Biochem Parasitol 145:101–110PubMedGoogle Scholar
  348. 348.
    Visser A, Geldhof P, DeMaere V et al (2006) Efficacy and specificity of RNA interference in larval life-stages of Ostertagia ostertagi. Parasitology 133:777–783PubMedGoogle Scholar
  349. 349.
    Zawadzki JL, Presidente PJ, Meeusen EN et al (2006) RNAi in Haemonchus contortus: a potential method for target validation. Trends Parasitol 22:495–499PubMedGoogle Scholar
  350. 350.
    Knox DP, Geldhof P, Visser A et al (2007) RNA interference in parasitic nematodes of animals: a reality check? Trends Parasitol 23:107–117Google Scholar
  351. 351.
    Samarasinghe B, Knox DP, Britton C (2011) Factors affecting susceptibility to RNA interference in Haemonchus contortus and in vivo silencing of an H11 aminopeptidase gene. Int J Parasitol 41:51–59PubMedGoogle Scholar
  352. 352.
    Viney ME, Thompson FJ (2008) Two hypotheses to explain why RNA interference does not work in animal parasitic nematodes. Int J Parasitol 38:43–47PubMedGoogle Scholar
  353. 353.
    Lok JB (2009) Transgenesis in parasitic nematodes: building a better array. Trends Parasitol 25:345–347PubMedCentralPubMedGoogle Scholar
  354. 354.
    Hu M, Lok JB, Ranjit N et al (2010) Structural and functional characterisation of the fork head transcription factor-encoding gene, Hc-daf-16, from the parasitic nematode Haemonchus contortus (Strongylida). Int J Parasitol 40:405–415PubMedCentralPubMedGoogle Scholar
  355. 355.
    Stepek G, McCormack G, Page AP (2010) Collagen processing and cuticle formation is catalysed by the astacin metalloprotease DPY-31 in free-living and parasitic nematodes. Int J Parasitol 40:533–542PubMedGoogle Scholar
  356. 356.
    Grant WN, Skinner SJ, Newton-Howes J et al (2006) Heritable transgenesis of Parastrongyloides trichosuri: a nematode parasite of mammals. Int J Parasitol 36:475–483PubMedGoogle Scholar
  357. 357.
    Liu L, Li Y, Li S et al (2012) Comparison of next-generation sequencing systems. J Biomed Biotechnol 2012:251364PubMedCentralPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Cinzia Cantacessi
    • 1
    • 3
  • Andreas Hofmann
    • 2
  • Bronwyn E. Campbell
    • 1
  • Robin B. Gasser
    • 1
    Email author
  1. 1.Department of Veterinary and Agricultural SciencesThe University of MelbourneParkvilleAustralia
  2. 2.Structural Chemistry Program, Eskitis InstituteGriffith UniversityBrisbaneAustralia
  3. 3.Department of Veterinary MedicineUniversity of CambridgeCambridgeUK

Personalised recommendations