Abstract
The term “high-content screening” has become synonymous with imaging screens using automated microscopes and automated image analysis. The term was coined a little over 10 years ago. Since then the technology has evolved considerably and has established itself firmly in the drug discovery and development industry. Both the instruments and the software controlling the instruments and analyzing the data have come to maturity, so the full benefits of high-content screening can now be realized. Those benefits are the capability of carrying out phenotypic multiparametric cellular assays in an unbiased, fully automated, and quantitative fashion. Automated microscopes and automated image analysis are being applied at all stages of the drug discovery and development pipeline. All major pharmaceutical companies have adopted the technology and it is in the process of being embraced broadly by the academic community. This review aims at describing the current capabilities and limits of the technology as well as highlighting necessary developments that are required to exploit fully the potential of high-content screening and analysis.
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Adams CP, Brantner VV (2010) Health Econ 19:130–141
Pearson H (2006) Nature 444:532–533
Hughes B (2008) Nat Rev Drug Discov 8:93–96
Nusslein-Volhard C, Wieschaus E (1980) Nature 287:795–801
Brenner S (1974) Genetics 77:71–94
Conrad C, Gerlich DW (2010) J Cell Biol 188:453–461
Niederlein A, Meyenhofer F, White D, Marc B (2009) Comb Chem High Throughput Screen 12:899–907
Zanella F, Carnero A (2009) Clin Transl Oncol 11:651–658
Evensen L, Micklem DR, Link W, Lorens JB (2010) Cytom A 77A:41–51
Daub A, Sharma P, Finkbeiner S (2009) Curr Opin Neurobiol 19:537–543
Kummel A, Gubler H, Gehin P, Beibel M, Gabriel D, Parker CN (2010) J Biomol Screen 15:95–101
Thomas N (2010) J Biomol Screen 15:1–9
Garavaglia A, Moiana A, Camnasio S, Bolognini D, Papait R, Rigamonti D, Cattaneo E (2010) BMC Neurosci 11:7
Xu G, Mawji I, Macrae C, Koch C, Datti A, Wrana J, Dennis J, Schimmer A (2008) Apoptosis 13:413–422
Santos AF, Zaltsman AB, Martin RC, Kuzmin A, Alexandrov Y, Roquemore EP, Jessop RA, Erck MGMv, Verheijen JH (2008) ASSAY Drug Devel Technol 6:693–710
Radio NM, Freudenrich TM, Robinette BL, Crofton KM, Mundy WR (2010) Neurotoxicol Teratol 32:25–35
Neumann B, Walter T, Hériché J-K, Bulkescher J, Erfle H, Conrad C, Rogers P, Poser I, Held M, Liebel U, Cetin C, Sieckmann F, Pau G, Kabbe R, Wünsche A, Satagopam V, Schmitz MHA, Chapuis C, Gerlich DW, Schneider R, Eils R, Huber W, Peters J-M, Hyman AA, Durbin R, Pepperkok R, Ellenberg J (2010) Nature 464:721–727
Christophe T, Jackson M, Jeon HK, Fenistein D, Contreras-Dominguez M, Kim J, Genovesio A, Carralot J-P, Ewann F, Kim EH, Lee SY, Kang S, Seo MJ, Park EJ, Skovierová H, Pham H, Riccardi G, Nam JY, Marsollier L, Kempf M, Joly-Guillou M-L, Oh T, Shin WK, No Z, Nehrbass U, Brosch R, Cole ST, Brodin P (2009) PLoS Pathog 5:e1000645
Desbordes SC, Placantonakis DG, Ciro A, Socci ND, Lee G, Djaballah H, Studer L (2008) Cell Stem Cell 2:602–612
Wolff M, Kauschke SG, Schmidt S, Heilker R (2008) J Biomol Screen 13:837–846
Chen S, Borowiak M, Fox JL, Maehr R, Osafune K, Davidow L, Lam K, Peng LF, Schreiber SL, Rubin LL, Melton D (2009) Nat Chem Biol 5:258–265
Prudencio M, Rodrigues CD, Hannus M, Martin C, Real E, Gonçalves LA, Carret C, Dorkin R, Röhl I, Jahn-Hoffmann K, Luty AJF, Sauerwein R, Echeverri CJ, Mota MM (2008) PLoS Pathog 4:e1000201
Ovcharenko D, Kelnar K, Johnson C, Leng N, Brown D (2007) Cancer Res 67:10782–10788
Xie FY, Woodle MC, Lu PY (2006) Drug Discov Today 11:67–73
Kiefer J, Yin HH, Que QQ, Mousses S (2009) Meth Mol Biol 563:275–287
Ovcharenko D, Jarvis R, Hunicke-Smith S, Kelnar K, Brown D (2005) RNA 11:985–993
Erfle H, Neumann B, Liebel U, Rogers P, Held M, Walter T, Ellenberg J, Pepperkok R (2007) Nat Protoc 2:392
Pelkmans L, Fava E, Grabner H, Hannus M, Habermann B, Krausz E, Zerial M (2005) Nature 436:78–86
Jackson AL, Burchard J, Schelter J, Chau BN, Cleary M, Lim L, Linsley PS (2006) RNA 12:1179–1187
Jackson AL, Bartz SR, Schelter J, Kobayashi SV, Burchard J, Mao M, Li B, Cavet G, Linsley PS (2003) Nat Biotechnol 21:635–637
Jackson AL, Burchard J, Leake D, Reynolds A, Schelter J, Guo J, Johnson JM, Lim L, Karpilow J, Nichols K, Marshall W, Khvorova A, Linsley PS (2006) RNA 12:1197–1205
Bramsen JB, Laursen MB, Nielsen AF, Hansen TB, Bus C, Langkjaer N, Babu BR, Hojland T, Abramov M, Van Aerschot A, Odadzic D, Smicius R, Haas J, Andree C, Barman J, Wenska M, Srivastava P, Zhou C, Honcharenko D, Hess S, Muller E, Bobkov GV, Mikhailov SN, Fava E, Meyer TF, Chattopadhyaya J, Zerial M, Engels JW, Herdewijn P, Wengel J, Kjems J (2009) Nucleic Acids Res 37:2867–2881
Huesken D, Lange J, Mickanin C, Weiler J, Asselbergs F, Warner J, Meloon B, Engel S, Rosenberg A, Cohen D, Labow M, Reinhardt M, Natt F, Hall J (2005) Nat Biotechnol 23:995–1001
Kittler R, Surendranath V, Heninger A-K, Slabicki M, Theis M, Putz G, Franke K, Caldarelli A, Grabner H, Kozak K, Wagner J, Rees E, Korn B, Frenzel C, Sachse C, Sonnichsen B, Guo J, Schelter J, Burchard J, Linsley PS, Jackson AL, Habermann B, Buchholz F (2007) Nat Meth 4:337–344
Echeverri CJ, Beachy PA, Baum B, Boutros M, Buchholz F, Chanda SK, Downward J, Ellenberg J, Fraser AG, Hacohen N, Hahn WC, Jackson AL, Kiger A, Linsley PS, Lum L, Ma Y, Mathey-Prevot B, Root DE, Sabatini DM, Taipale J, Perrimon N, Bernards R (2006) Nat Meth 3:777
Li Z, Yan Y, Powers EA, Ying X, Janjua K, Garyantes T, Baron B (2003) J Biomol Screen 8:489
Almholt DLC, Loechel F, Nielsen SJ, Krog-Jensen C, Terry R, Bjørn SP, Pedersen HC, Praestegaard M, Møller S, Heide M, Pagliaro L, Mason AJ, Butcher S, Dahl SW (2004) Assay Drug Dev Technol 2:7
Paran Y, Ilan M, Kashman Y, Goldstein S, Liron Y, Geiger B, Kam Z (2007) J Struct Biol 158:233
Bordet T, Buisson B, Michaud M, Drouot C, Galea P, Delaage P, Akentieva NP, Evers AS, Covey DF, Ostuni MA, Lacapere J-J, Massaad C, Schumacher M, Steidl E-M, Maux D, Delaage M, Henderson CE, Pruss RM (2007) J Pharmacol Exp Ther 322:709–720
Ross DA, Lee S, Reiser V, Xue J, Alves K, Vaidya S, Kreamer A, Mull R, Hudak E, Hare T, Detmers PA, Lingham R, Ferrer M, Strulovici B, Santini F (2008) J Biomol Screen 13:449–455
Vogt A, Cooley KA, Brisson M, Tarpley MG, Wipf P, Lazo JS (2003) Chem Biol 10:733
Hoffman AF, Garippa RJ (2008) HCS for HTS. Wiley, Hoboken
Perlman ZE, Slack MD, Feng Y, Mitchison TJ, Wu LF, Altschuler SJ (2004) Science 306:1194
Barabasz A, Foley B, Otto JC, Scott A, Rice J (2006) Assay Drug Dev Technol 4:153
Young DW, Bender A, Hoyt J, McWhinnie E, Chirn G-W, Tao CY, Tallarico JA, Labow M, Jenkins JL, Mitchison TJ, Feng Y (2008) Nat Chem Biol 4:59–68
Loo L-H, Wu LF, Altschuler SJ (2007) Nat Meth 4:445–453
Durr O, Duval F, Nichols A, Lang P, Brodte A, Heyse S, Besson D (2007) J Biomol Screen 12:1042–1049
Unterreiner V, Ibig-Rehm Y, Simonen M, Gubler H, Gabriel D (2009) J Biomol Screen 14:59–65
Wunberg T, Hendrix M, Hillisch A, Lobell M, Meier H, Schmeck C, Wild H, Hinzen B (2006) Drug Discov Today 11:175–180
O’Brien P, Irwin W, Diaz D, Howard-Cofield E, Krejsa C, Slaughter M, Gao B, Kaludercic N, Angeline A, Bernardi P, Brain P, Hougham C (2006) Arch Toxicol 80:580–604
Abraham VC, Towne DL, Waring JF, Warrior U, Burns DJ (2008) J Biomol Screen 13:527–537
Slack MD, Martinez ED, Wu LF, Altschuler SJ (2008) Proc Natl Acad Sci USA 105:19306–19311
Jones TR, Carpenter AE, Lamprecht MR, Moffat J, Silver SJ, Grenier JK, Castoreno AB, Eggert US, Root DE, Golland P, Sabatini DM (2009) Proc Natl Acad Sci USA 106:1826–1831
Wang J, Zhou X, Li F, Bradley PL, Chang S-F, Perrimon N, Wong STC (2009) J Biomed Inform 42:32–40
Yin Z, Zhou X, Bakal C, Li F, Sun Y, Perrimon N, Wong S (2008) BMC Bioinform 9:264
Kozak K, Agrawal A, Machuy N, Csucs G (2009) J Comput Sci Syst Biol 2:219–239
Jan E, Byrne SJ, Cuddihy M, Davies AM, Volkov Y, Gun'ko YK, Kotov NA (2008) ACS Nano 2:928–938
Krajewska M, Smith LH, Rong J, Huang X, Hyer ML, Zeps N, Iacopetta B, Linke SP, Olson AH, Reed JC, Krajewski S (2009) J Histochem Cytochem 57:649–663
Pan C, Kumar C, Bohl S, Klingmueller U, Mann M (2009) Mol Cell Proteomics 8:443–450
Lloyd S, Hayden MJ, Sakai Y, Fackett A, Silber PM, Hewitt NJ, Li AP (2002) Chem Biol Interact 142:57–71
Baron U, Türbachova I, Hellwag A, Eckhardt F, Berlin K, Hoffmuller U, Gardina P, Olek S (2006) Epigenetics 1:55–60
Marshak DR, Greenwalt DE (2006) In: Taylor DL, Haskins JR, Giuliano KA (eds) High content screening: a powerful approach to systems cell biology and drug discovery. Methods in molecular biology, vol 356. Humana, Totowa, pp 121–128
DeLoid GM, Sulahian TH, Imrich A, Kobzik L (2009) PLoS ONE 4:e6209
Tobias W, Gerhard L, Margot G, Gerd S (2006) Cytom A 69A:200–202
Morelli J, Buehrle M, Pognan F, Barone L, Fieles W, Ciaccio P (2006) Cell Biol Toxicol 22:15–27
Basiji DA, Ortyn WE, Liang L, Venkatachalam V, Morrissey P (2007) Clin Lab Med 27:653
Beletskii MCA, Sriraman P, Chiriac C, Zhao L, Abbot S, Yu L (2005) Biotechniques 39:894–897
Rosenthal A, Mork P, Li MH, Stanford J, Koester D, Reynolds P (2010) J Biomed Inform 43:342–353
Garcia Ruiz M, Garcia Chaves A, Ruiz Ibañez C, Gutierrez Mazo J, Ramirez Giraldo J, Pelaez Echavarria A, Valencia Diaz E, Pelaez Restrepo G, Montoya Munera E, Garcia Loaiza B, Gomez Gonzalez S (2010) J Digit Imaging (in press). doi:10.1007/s10278-009-9265-x
Snijder B, Sacher R, Ramo P, Damm E-M, Liberali P, Pelkmans L (2009) Nature 461:520–523
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Bickle, M. The beautiful cell: high-content screening in drug discovery. Anal Bioanal Chem 398, 219–226 (2010). https://doi.org/10.1007/s00216-010-3788-3
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DOI: https://doi.org/10.1007/s00216-010-3788-3