Yearb Med Inform 2010; 19(01): 75-81
DOI: 10.1055/s-0038-1638694
Original Article
Georg Thieme Verlag KG Stuttgart

In Cereo and in Silico: Tissue Microarray (TMA) Techniques and Bioinformatics Are Thriving Forces in Medical Science and Personalized Medicine

E. Lang
1   h_da Darmstadt University, School of Media, Section Information Science & Engineering, Darmstadt, Germany
› Institutsangaben
Weitere Informationen

Correspondence to:

Elke Lang
h_da Darmstadt University
School of Media
Section Information Science & Engineering
Haardtring 100
D-64295 Darmstadt
Germany
Telefon: +49 6151 169416   

Publikationsverlauf

Publikationsdatum:
07. März 2018 (online)

 

Summary

Objectives: Tissue microarray (TMA) techniques are among the most promising developments in biomedicine during the last decade. Bioinformatics techniques are indispensable for storing and processing the masses of data related with tissue archive administration and investigation of raw data. Interrelationship between experimental and computational work will be shown.

Methods: Tissue specimen arrays allow parallel analysis of huge amounts of samples. TMA techniques thus produce enormous masses of raw data, and optimal use of data can only be made using modern bioinformatics techniques based on huge storage systems, scalable multilayer software architecture and high-throughput algorithms for retrieval and statistical processing. Further crucial issues addressed by informatics techniques are specimen identification during the whole processing chain, and anonymization whenever scientific work is performed without regard to a certain patient.

Results: TMA supported by bioinformatics methods has helped in identification of biomarkers, mainly in cancer diagnosis. Moreover, it provides powerful means of quality assurance and training in histopathology.

Conclusions: Further statistical analyses seem to be necessary to detect if certain biomarkers are present in nearly all kinds of specimen of the concerned patient, which would allow effective mass screening based on easily accessible specimen. Some investigations showed low dependence on the specimen localization, whereas others suggest to be extremely careful in material selection for the recipient block.


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  • References

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  • 2 Broder S, Venter JC. Sequencing the entire genomes of free-living organisms: the foundation of pharmacology in the new millennium. Annu Rev Pharmacol Toxicol 2000; 40: 97-132.
  • 3 Schuster SC, Miller W, Ratan A, Tomsho LP, Giardine B, Kasson LR. et al. Complete Khoisan and Bantu genomes from southern Africa. Nature 2010; Feb 18; 463 (7283): 943-7.
  • 4 Mir KU. Sequencing genomes: from individuals to populations. Brief Funct Genomic Proteomic 2009; Sep; 08 (05) 367-78.
  • 5 Riffle M, Eng JK. Proteomics data repositories. Proteomics 2009; Oct; 09 (20) 4653-63.
  • 6 Vermeulen M, Selbach M. Quantitative proteomics: a tool to assess cell differentiation. Curr Opin Cell Biol 2009; Dec; 21 (06) 761-6.
  • 7 Vinayavekhin N, Homan EA, Saghatelian A. Exploring disease through metabolomics. ACS Chem Biol 2010; Jan 15; 05 (01) 91-103.
  • 8 von der Lieth CW, Bohne-Lang A, Lohmann KK, Frank M. Bioinformatics for glycomics: status, methods, requirements and perspectives. Brief Bioinform 2004; Jun; 05 (02) 164-78.
  • 9 Orlando R. Quantitative glycomics. Methods Mol Biol 2010; 600: 31-49.
  • 10 Li J, Richards JC. Functional glycomics and glycobiology: an overview. Methods Mol Biol 2010; 600: 1-8.
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  • 13 Jawhar NM. Tissue Microarray: A rapidly evolving diagnostic and research tool. Ann Saudi Med 2009; Mar-Apr; 29 (02) 123-7.
  • 14 Avninder S, Ylaya K, Hewitt SM. Tissue microarray: a simple technology that has revolutionized research in pathology. J Postgrad Med 2008; Apr-Jun;54 (02) 158-62.
  • 15 Wang L, Deavers MT, Malpica A, Silva EG, Liu J. Tissue macroarray: a simple and cost-effective method for high-throughput studies. Appl Immunohistochem Mol Morphol 2003; Jun; 11 (02) 174-6.
  • 16 Ma H, Horiuchi KY. Chemical microarray: a new tool for drug screening and discovery. Drug Discov Today 2006; Jul; 11 (13-14): 661-8.
  • 17 Fernandes TG, Diogo MM, Clark DS, Dordick JS, Cabral JM. High-throughput cellular microarray platforms: applications in drug discovery, toxicology and stem cell research. Trends Biotechnol 2009; Jun; 27 (06) 342-9.
  • 18 Eguíluz C, Viguera E, Millán L, Pérez J. Multitissue array review: a chronological description of tissue array techniques, applications and procedures. Pathol Res Pract 2006; 202 (08) 561-8.
  • 19 Battifora H. The multitumor (sausage) tissue block: novel method for immunohistochemical antibody testing. Lab Invest 1986; Aug; 55 (02) 244-8.
  • 20 Wan WH, Fortuna MB, Furmanski P. A rapid and efficient method for testing immunohistochemical reactivity of monoclonal antibodies against multiple tissue samples simultaneously. J Immunol Methods 1987; Oct 23; 103 (01) 121-9.
  • 21 Battifora H, Mehta P. The checkerboard tissue block. An improved multitissue control block. Lab Invest 1990; Nov; 63 (05) 722-4.
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  • 25 Morgan HL. The Generation of a Unique Machine Description for Chemical Structures A - Technique Developed at Chemical Abstracts Service. J Chem Doc 1965; 05: 107-13.
  • 26 Lang E, Förster T, Lieth CW. The integration of the CCDF into the relational information network of the German Cancer Research Center. Gasteiger J. editor. Software development in chemistry 4. Heidelberg: Springer; 1990: 43-50.
  • 27 Camp RL, Neumeister V, Rimm DL. A decade of tissue microarrays: progress in the discovery and validation of cancer biomarkers. J Clin Oncol 2008; Dec 1; 26 (34) 5630-7.
  • 28 Kennard O, Speakman JC, Donnay JDH. Primary crystallographic data. Acta Cryst 1967; 22: 445-9.
  • 29 Motherwell WDS. The CSD-450,000 answers … but what are the questions?. Cryst Rev 2008; 14: 97-116.
  • 30 Bernstein FC, Koetzle TF, Williams GJ, Meyer Jr EF, Brice MD, Rodgers JR. et al. The Protein Data Bank: a computer-based archival f ile for macromolecular structures. J Mol Biol 1977; May 25; 112 (03) 535-42.
  • 31 Ranzinger R, Frank M, von der Lieth CW, Herget S. Glycome-DB.org: a portal for querying across the digital world of carbohydrate sequences. Glycobiology 2009; Dec; 19 (12) 1563-7.
  • 32 Bairoch A. The ENZYME database in 2000. Nucleic Acids Res 2000; 28: 304-5.
  • 33 Sayers EW, Barrett T, Benson DA, Bolton E, Bryant SH, Canese K. et al. Database resources of the National Center for Biotechnology Information. Nucleic Acids Res 2010; Jan;38(Database issue): D5-16.
  • 34 Barrett T, Troup DB, Wilhite SE, Ledoux P, Rudnev D, Evangelista C. et al. NCBI GEO: archive for high-throughput functional genomic data. Nucleic Acids Res 2009; Jan;37(Database issue): D885-90.
  • 35 Conway C, Dobson L, O’Grady A, Kay E, Costello S, O’Shea D. Virtual microscopy as an enabler of automated/quantitative assessment of protein expression in TMAs. Histochemistry and Cell Biology 2008; 130: 447-63.
  • 36 Conway C, O’Shea D, O’Brien S, Lawler DK, Dodrill GD, O’Grady A. et al. The development and validation of the Virtual Tissue Matrix, a software application that facilitates the review of tissue microarrays on line. BMC Bioinformatics 2006; 07: 256.
  • 37 Sharma-Oates A, Quirke P, Westhead DR. TmaDB: a repository for tissue microarray data. BMC Bioinformatics 2005; Sep 1; 06: 218.
  • 38 Della VMea, Bortolotti N, Beltrami CA. eSlide suite: an open source software system for whole slide imaging. J Clin Pathol 2009; Aug; 62 (08) 749-51.
  • 39 Thallinger GG, Baumgartner K, Pirklbauer M, Uray M, Pauritsch E, Mehes G. et al. TAMEE: data management and analysis for tissue microarrays. BMC Bioinformatics 2007; 08: 81.
  • 40 Della VMea, Bin I, Pandolfi M, Di Loreto C. A web-based system for tissue microarray data management. Diagn Pathol 2006; Oct 11; 01: 36.
  • 41 Marinelli RJ, Montgomery K, Liu CL, Shah NH, Prapong W, Nitzberg M. et al. The Stanford Tissue Microarray Database. Nucleic Acids Res 2008; Jan;36(Database issue): D871-7.
  • 42 Viti F, Merelli I, Caprera A, Lazzari B, Stella A, Milanesi L. Ontology-based, Tissue MicroArray oriented, image centered tissue bank. BMC Bioinformatics 2008; Apr 25; 9 Suppl 4: S4.
  • 43 Stokes TH, Torrance JT, Li H, Wang MD. ArrayWiki: an enabling technology for sharing public microarray data repositories and meta-analyses. BMC Bioinformatics 2008; May 28;9 Suppl 6: S18.
  • 44 Uhlén M, Björling E, Agaton C, Szigyarto CA, Amini B, Andersen E. et al. A Human Protein Atlas for Normal and Cancer Tissues Based on Antibody Proteomics. Mol Cell Proteomics 2005; 04 (12) 1920-32.
  • 45 Berglund L, Björling E, Oksvold P, Fagerberg L, Asplund A, Szigyarto CA, Persson A. et al. A genecentric Human Protein Atlas for expression profiles based on antibodies. Mol Cell Proteomics 2008; Oct; 07 (10) 2019-27.
  • 46 Schobesberger M, Baltzer A, Oberli A, Kappeler A, Gugger M, Burger H. et al. Gene expression variation between distinct areas of breast cancer measured from paraffin-embedded tissue cores. BMC Cancer 2008; Nov 25; 08: 343.
  • 47 Dudley JT, Tibshirani R, Deshpande T, Butte AJ. Disease signatures are robust across tissues and experiments. Mol Syst Biol 2009; 05: 307.
  • 48 Camp RL, Charette LA, Rimm DL. Validation of tissue microarray technology in breast carcinoma. Lab Invest 2000; Dec; 80 (12) 1943-9.
  • 49 Torhorst J, Bucher C, Kononen J, Haas P, Zuber M, Köchli OR. et al. Tissue microarrays for rapid linking of molecular changes to clinical endpoints. Am J Pathol 2001; Dec; 159 (06) 2249-56.
  • 50 Finak G, Sadekova S, Pepin F, Hallett M, Meterissian S, Halwani F. et al. Gene expression signatures of morphologically normal breast tissue identify basal-like tumors. Breast Cancer Res 2006; 08 (05) R58.

Correspondence to:

Elke Lang
h_da Darmstadt University
School of Media
Section Information Science & Engineering
Haardtring 100
D-64295 Darmstadt
Germany
Telefon: +49 6151 169416   

  • References

  • 1 Venter JC, Adams MD, Martin-Gallardo A, McCombie WR, Fields C. Genome sequence analysis: scientif ic objectives and practical strategies. Trends Biotechnol 1992; Jan-Feb; 10 (1-2): 8-11.
  • 2 Broder S, Venter JC. Sequencing the entire genomes of free-living organisms: the foundation of pharmacology in the new millennium. Annu Rev Pharmacol Toxicol 2000; 40: 97-132.
  • 3 Schuster SC, Miller W, Ratan A, Tomsho LP, Giardine B, Kasson LR. et al. Complete Khoisan and Bantu genomes from southern Africa. Nature 2010; Feb 18; 463 (7283): 943-7.
  • 4 Mir KU. Sequencing genomes: from individuals to populations. Brief Funct Genomic Proteomic 2009; Sep; 08 (05) 367-78.
  • 5 Riffle M, Eng JK. Proteomics data repositories. Proteomics 2009; Oct; 09 (20) 4653-63.
  • 6 Vermeulen M, Selbach M. Quantitative proteomics: a tool to assess cell differentiation. Curr Opin Cell Biol 2009; Dec; 21 (06) 761-6.
  • 7 Vinayavekhin N, Homan EA, Saghatelian A. Exploring disease through metabolomics. ACS Chem Biol 2010; Jan 15; 05 (01) 91-103.
  • 8 von der Lieth CW, Bohne-Lang A, Lohmann KK, Frank M. Bioinformatics for glycomics: status, methods, requirements and perspectives. Brief Bioinform 2004; Jun; 05 (02) 164-78.
  • 9 Orlando R. Quantitative glycomics. Methods Mol Biol 2010; 600: 31-49.
  • 10 Li J, Richards JC. Functional glycomics and glycobiology: an overview. Methods Mol Biol 2010; 600: 1-8.
  • 11 Bohne-Lang A, Lang E, Förster T, von der Lieth CW. LINUCS: linear notation for unique description of carbohydrate sequences. Carbohydr Res 2001; Nov 1; 336 (01) 1-11.
  • 12 Sanger F, Nicklen S, Coulson AR. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A 1977; Dec; 74 (12) 5463-7.
  • 13 Jawhar NM. Tissue Microarray: A rapidly evolving diagnostic and research tool. Ann Saudi Med 2009; Mar-Apr; 29 (02) 123-7.
  • 14 Avninder S, Ylaya K, Hewitt SM. Tissue microarray: a simple technology that has revolutionized research in pathology. J Postgrad Med 2008; Apr-Jun;54 (02) 158-62.
  • 15 Wang L, Deavers MT, Malpica A, Silva EG, Liu J. Tissue macroarray: a simple and cost-effective method for high-throughput studies. Appl Immunohistochem Mol Morphol 2003; Jun; 11 (02) 174-6.
  • 16 Ma H, Horiuchi KY. Chemical microarray: a new tool for drug screening and discovery. Drug Discov Today 2006; Jul; 11 (13-14): 661-8.
  • 17 Fernandes TG, Diogo MM, Clark DS, Dordick JS, Cabral JM. High-throughput cellular microarray platforms: applications in drug discovery, toxicology and stem cell research. Trends Biotechnol 2009; Jun; 27 (06) 342-9.
  • 18 Eguíluz C, Viguera E, Millán L, Pérez J. Multitissue array review: a chronological description of tissue array techniques, applications and procedures. Pathol Res Pract 2006; 202 (08) 561-8.
  • 19 Battifora H. The multitumor (sausage) tissue block: novel method for immunohistochemical antibody testing. Lab Invest 1986; Aug; 55 (02) 244-8.
  • 20 Wan WH, Fortuna MB, Furmanski P. A rapid and efficient method for testing immunohistochemical reactivity of monoclonal antibodies against multiple tissue samples simultaneously. J Immunol Methods 1987; Oct 23; 103 (01) 121-9.
  • 21 Battifora H, Mehta P. The checkerboard tissue block. An improved multitissue control block. Lab Invest 1990; Nov; 63 (05) 722-4.
  • 22 Kononen J, Bubendorf L, Kallioniemi A, Bärlund M, Schraml P, Leighton S. et al. Tissue microarrays for high-throughput molecular profiling of tumor specimens. Nat Med 1998; Jul;4 (07) 844-7.
  • 23 Dunlay RT, Czekalski WJ, Collins MA. Overview of informatics for high content screening. Methods Mol Biol 2007; 356: 269-80.
  • 24 Dittmar PG, Farmer NA, Fisanick W, Haines RC, Mockus J. The CAS ONLINE search system. 1. General system design and selection, generation, and use of search screens. J Chem Inform Comput Sci 1983; 23: 93-102.
  • 25 Morgan HL. The Generation of a Unique Machine Description for Chemical Structures A - Technique Developed at Chemical Abstracts Service. J Chem Doc 1965; 05: 107-13.
  • 26 Lang E, Förster T, Lieth CW. The integration of the CCDF into the relational information network of the German Cancer Research Center. Gasteiger J. editor. Software development in chemistry 4. Heidelberg: Springer; 1990: 43-50.
  • 27 Camp RL, Neumeister V, Rimm DL. A decade of tissue microarrays: progress in the discovery and validation of cancer biomarkers. J Clin Oncol 2008; Dec 1; 26 (34) 5630-7.
  • 28 Kennard O, Speakman JC, Donnay JDH. Primary crystallographic data. Acta Cryst 1967; 22: 445-9.
  • 29 Motherwell WDS. The CSD-450,000 answers … but what are the questions?. Cryst Rev 2008; 14: 97-116.
  • 30 Bernstein FC, Koetzle TF, Williams GJ, Meyer Jr EF, Brice MD, Rodgers JR. et al. The Protein Data Bank: a computer-based archival f ile for macromolecular structures. J Mol Biol 1977; May 25; 112 (03) 535-42.
  • 31 Ranzinger R, Frank M, von der Lieth CW, Herget S. Glycome-DB.org: a portal for querying across the digital world of carbohydrate sequences. Glycobiology 2009; Dec; 19 (12) 1563-7.
  • 32 Bairoch A. The ENZYME database in 2000. Nucleic Acids Res 2000; 28: 304-5.
  • 33 Sayers EW, Barrett T, Benson DA, Bolton E, Bryant SH, Canese K. et al. Database resources of the National Center for Biotechnology Information. Nucleic Acids Res 2010; Jan;38(Database issue): D5-16.
  • 34 Barrett T, Troup DB, Wilhite SE, Ledoux P, Rudnev D, Evangelista C. et al. NCBI GEO: archive for high-throughput functional genomic data. Nucleic Acids Res 2009; Jan;37(Database issue): D885-90.
  • 35 Conway C, Dobson L, O’Grady A, Kay E, Costello S, O’Shea D. Virtual microscopy as an enabler of automated/quantitative assessment of protein expression in TMAs. Histochemistry and Cell Biology 2008; 130: 447-63.
  • 36 Conway C, O’Shea D, O’Brien S, Lawler DK, Dodrill GD, O’Grady A. et al. The development and validation of the Virtual Tissue Matrix, a software application that facilitates the review of tissue microarrays on line. BMC Bioinformatics 2006; 07: 256.
  • 37 Sharma-Oates A, Quirke P, Westhead DR. TmaDB: a repository for tissue microarray data. BMC Bioinformatics 2005; Sep 1; 06: 218.
  • 38 Della VMea, Bortolotti N, Beltrami CA. eSlide suite: an open source software system for whole slide imaging. J Clin Pathol 2009; Aug; 62 (08) 749-51.
  • 39 Thallinger GG, Baumgartner K, Pirklbauer M, Uray M, Pauritsch E, Mehes G. et al. TAMEE: data management and analysis for tissue microarrays. BMC Bioinformatics 2007; 08: 81.
  • 40 Della VMea, Bin I, Pandolfi M, Di Loreto C. A web-based system for tissue microarray data management. Diagn Pathol 2006; Oct 11; 01: 36.
  • 41 Marinelli RJ, Montgomery K, Liu CL, Shah NH, Prapong W, Nitzberg M. et al. The Stanford Tissue Microarray Database. Nucleic Acids Res 2008; Jan;36(Database issue): D871-7.
  • 42 Viti F, Merelli I, Caprera A, Lazzari B, Stella A, Milanesi L. Ontology-based, Tissue MicroArray oriented, image centered tissue bank. BMC Bioinformatics 2008; Apr 25; 9 Suppl 4: S4.
  • 43 Stokes TH, Torrance JT, Li H, Wang MD. ArrayWiki: an enabling technology for sharing public microarray data repositories and meta-analyses. BMC Bioinformatics 2008; May 28;9 Suppl 6: S18.
  • 44 Uhlén M, Björling E, Agaton C, Szigyarto CA, Amini B, Andersen E. et al. A Human Protein Atlas for Normal and Cancer Tissues Based on Antibody Proteomics. Mol Cell Proteomics 2005; 04 (12) 1920-32.
  • 45 Berglund L, Björling E, Oksvold P, Fagerberg L, Asplund A, Szigyarto CA, Persson A. et al. A genecentric Human Protein Atlas for expression profiles based on antibodies. Mol Cell Proteomics 2008; Oct; 07 (10) 2019-27.
  • 46 Schobesberger M, Baltzer A, Oberli A, Kappeler A, Gugger M, Burger H. et al. Gene expression variation between distinct areas of breast cancer measured from paraffin-embedded tissue cores. BMC Cancer 2008; Nov 25; 08: 343.
  • 47 Dudley JT, Tibshirani R, Deshpande T, Butte AJ. Disease signatures are robust across tissues and experiments. Mol Syst Biol 2009; 05: 307.
  • 48 Camp RL, Charette LA, Rimm DL. Validation of tissue microarray technology in breast carcinoma. Lab Invest 2000; Dec; 80 (12) 1943-9.
  • 49 Torhorst J, Bucher C, Kononen J, Haas P, Zuber M, Köchli OR. et al. Tissue microarrays for rapid linking of molecular changes to clinical endpoints. Am J Pathol 2001; Dec; 159 (06) 2249-56.
  • 50 Finak G, Sadekova S, Pepin F, Hallett M, Meterissian S, Halwani F. et al. Gene expression signatures of morphologically normal breast tissue identify basal-like tumors. Breast Cancer Res 2006; 08 (05) R58.