Updated July 26, 1992 - GELLAB-I+II PAPERS-2.0
Revised 3-21-96
We will introduce these papers with a short suggested reading list of papers which cover GELLAB concepts (I). GELLAB algorithms are cross-referenced by topic (II). Applications of GELLAB to biomedical area is cross-referenced by material (III).
The papers are ordered by date with a list of these references at the end of the introduction. Papers are indexed by topic with cross references where appropriate. A good place to start is short papers [4] and [10] which introduce the basic concepts and algorithms. More detailed versions of this material is in [7-9] which covers GELLAB segmentation, gel-pairing, and database respectively. An updated condensed version is in [15]. Additions to the basic GELLAB system which evolved as users exercised it with different requirements are discussed [11-12, 15, 17-18, 20, 22, 24, 27-28]. The new GELLAB-II system is discussed in summary papers [27-30].
I. Introduction to GELLAB
II. Algorithms used in GELLAB
III. Application of GELLAB to biological problems
IV. GELLAB-II
As can be seen from the sequence of papers, GELLAB had started out on a PDP8e controlled special-purpose image processor called the RTPP (Real Time Picture Processor constructed by the Image Processing Section under Lewis Lipkin [2]) and was written in FORTRAN [1-3]. Users of the initial PDP8e based system performed and recorded all measurements using the interactive system - one gel pair and one spot at a time. A decision was made to automate aspects of the measurement and recording procedures which were being done manually - and so the beginnings of GELLAB were implemented on the PDP8e. It quickly outstripped the computational capacity of the PDP8e and was then rewritten in SAIL [O.1] to run on a small DECsystem-10 (model 2020) connected to the PDP8e/RTPP. The RTPP was then used as an image I/O device. The SAIL version of GELLAB [4, 7-9] has been successfully exported to several sites which had DECsystem-10 or -20 computers. The RTPP `front end' was replaced at these other sites with various image I/O facilities. Graphics terminal realizations of Rmap and mosaics was added to facilitate user interaction when direct gray scale image I/O was not on-line or the user was dialing in to GELLAB from a remote terminal.
In 1984, a decision was made to export GELLAB to other less expensive and more readily available (i.e. portable) computing environments. Because of the extensive amount of SAIL code involved (about 70,000 lines) a machine translation of the SAIL code to the target portable language (C was selected) was required. The PSAIL, Portable SAIL, compiler [23, 25] is a portable SAIL to C compiler capable of translating SAIL source code programs into portable C programs. PSAIL had been running on the DECsystem-10 since 1985 and was used to convert the GELLAB programs to C.
The new C/UNIX based GELLAB is called GELLAB-II and the the older SAIL/DECsystem-10 (-20) based system, GELLAB-I. GELLAB-II is being debugged and reimplemented in a UNIX windowing environment. The windowing system selected is the X-windows system which is a public domain system from Project Athena at MIT [0.2]. Initially, GELLAB-II will be brought up on a SUN and latter, to some degree, on other UNIX machines.
In addition, a CRADA was established between IPS/NCI/FCRDC and Scanalytics/CSPI of Billerica, MA to make a low cost commerical version of the GELLAB-II 2D gel analysis software available on a low cost PC platform. This will provide potential users of GELLAB with better support and wider access. As most investigators are not interested or capable of installing or maintaining complex software, we feel that this commercialization will provide them with a high level of support and free us from this burden. The new version of the system is also being enhanced during this technology transfer process to improve the user interface and make software maintenance and support easier. It will be marketed and supported as GELLAB-II+ initially in Windows and Windows-NT versions running on inexpensive PC computers.
As some of the capability of the SAIL environment on the DECsystem-10 required for GELLAB does not exist in C/UNIX, it had to be emulated. Two major subsystems which are used extensively in GELLAB are the SAIL LEAP associative language [O.1, O.3, 25] and the OMNIGRAPH 2D and 3D graphics library [O.4]. These are emulated in two separately compiled packages LEPCGL and SMDISP respectively. LEPCGL implements a subset of LEAP including items, sets, lists and all of the operations on them. It has been in use for several months. SMDISP emulates a subset of OMNIGRAPH required for GELLAB. Unlike OMNIGRAPH which handled a variety of graphics terminals, SMDISP generates popup X11 graphics displays or Tektronix-4010 type terminal graphics which can be passed through a UNIX filter to PostScript laser printers.
The RTPP image processor used for image acquisition and display in GELLAB-I has been replaced by various X-Windows programs in GELLAB-II. Image display and manipulation is now done using the Xpix which runs under the X-windows system. Xpix runs on 8-bit (or greater) high resolution color graphics UNIX workstations.
Our local gel scanning data acquisition is done using either a Molecular Dynamics 300E laser densitometer or a high resolution CCD camera connected to one of our SUN computers. In addition, BioImage gel image data may be used by converting their scanned gel image files to our format. Gel accessioning is done using the getacc program. This program combines information linking each gel accession number, gel image file, region of interest in the gel image, OD calibration of the image file, and experiment information.
Landmarking is done using X-Windows programs landmark. Part of the landmarking process allows the user to flicker-compare two images for verifying alignment and this is quite usable with standard SUN workstations.
The composite gel database program cgelp has been upgraded in GELLAB-II and renamed cgelp2. It now contains an optional graphical user interface with pull-down menus, popup windows and a dynamic Rmap image where the user can directly interact with spots of interest and see spots the program has under consideration.
As a result, the graphics and data acquisition subsystems of GELLAB-II are quite usable under UNIX and X-Windows. The current GELLAB UNIX/C code now constitutes over 250,000 lines of C code (as of Version 1.3.53) in over 25 programs and currently runs best on SUN4 workstations.
1. Lemkin, P., Merril, C., Lipkin, L., Van Keuren, M., Oertel, W., Shapiro, B., Wade, M., Schultz, M., Smith, E., Software aids for the analysis of 2D gel electrophoresis images, Computers and Biomedical Research 12, 517-544, 1979.
2. Lemkin, P., Lipkin, L., BMON2 - A distributed monitor system for biological image processing. Computer Programs in Biomedicine 11, 21-42, 1980.
3. Lemkin, P., Lipkin, L., Merril, C., Shiffrin, S., Protein abnormalities in macrophages bearing asbestos. Environmental Health Perspectives 34, 75-89, 1980. NIEHS Conf. Medical Aspects of Mineral Fibers, 1979.
4. Lipkin, L.E., Lemkin, P.F., Data base techniques for multiple PAGE (2D gel) analysis. Clinical Chemistry 26, 1403-1413, 1980.
5. Lester, E.P., Lemkin, P., Lipkin, L.E., Cooper, H.L., Computer-assisted analysis of two-dimensional electrophoresis of human peripheral blood lymphocytes, Clinical Chemistry 26, 1392-1402 1980.
6. Lester, E.P., Lemkin, P., Lipkin, L.E., Cooper, H.L., Two - Dimensional electrophoretic analysis of protein synthesis in resting and growing lymphocytes in Vitro, J. Immunology, 126, 1428-1434, 1981.
7. Lemkin, P., Lipkin, L., GELLAB: A computer system for 2D gel electrophoresis analysis. I. Segmentation and preliminaries. Computers and Biomedical Research 14, 272-297, 1981.
8. Lemkin, P., Lipkin, L., GELLAB: A computer system for 2D gel electrophoresis analysis. II. Spot pairing, Computers and Biomedical Research 14, 355-380, 1981.
9. Lemkin, P., Lipkin, L., GELLAB: A computer system for 2D gel electrophoresis analysis. III. Multiple gel analysis. Computers and Biomedical Research 14, 407-446, 1981.
10. Lester, E.P., Lemkin, P.F., Lipkin, L.E., New dimensions in protein analysis - 2D gels coming of age through image processing, invited paper, Analytical Chemistry 53, 390A-397A, 1981.
11. Lemkin, P.F., Lipkin, L.E., GELLAB: multiple 2D electrophoretic gel analysis, in Electrophoresis '81, R. Allen, Arnaud (eds), W. De Gruyter, New York. 401-411, 1981.
12. Lemkin, P.F., Lipkin, L.E., Lester, E.P., Some extensions to the GELLAB 2D electrophoresis gel analysis system. Paper given at `Clinical Applications of 2D Electrophoresis', Mayo Clinic, Nov. 15-18, 1981. Clinical Chemistry 28, 840-849, 1982.
13. Lester, E.P., Lemkin, P.F., Lipkin, L.E., A two-dimensional Gel analysis of autologous T and B lymphoblastoid cell lines, Clinical Chemistry 28, 828-839, 1982.
14. Lester, E.P., Lemkin, P.F., Lowery, J.F., Lipkin, L.E., Human leukemias: A preliminary 2D electrophoretic analysis, Electrophoresis 3, 364-375, 1982.
15. Lemkin, P.F., Lipkin, L.E., Database techniques for 2D electrophoretic gel analysis, in Computing in Biological Science, Elsevier/North-Holland, M. Geisow, A. Barrett (eds), 181-226 1983.
16. Lester, E.P., Lemkin, P.F., Lipkin, L.E., States of differentiation in leukemias: A 2D gel analysis. In Chromosomes and Cancer: From Molecules to Man, Proceedings of 5th Annual Bristol Myers Symposium on Cancer Research. 1983, Academic Press, pp 226-245,
17. Lemkin, P.F., Lipkin, L.E., 2D Electophoresis gel data base analysis: Aspects of data structures and search strategies in GELLAB, Electrophoresis 4, 71-81, 1983. Presented at `Argonne Workshop on Technical advances in 2D electrophoresis and clinical applications of the technique', Aug. 29-Sep.1, 1982.
18. Howard, R.J., Aley, S.B., Lemkin, P.F., High resolution comparison of Plasmodium Knowlesi clones of different variant antigen phenotypes by 2D gel electrophoresis and computer analysis. Electrophoresis 4, 420-427, 1983.
19. Lester, E.P., Lemkin, P.F., Lipkin, L.E.: Protein indexing in leukemias and lymphomas, NY Acad. Sci. 428, 158-172, 1984.
20. Lemkin, P., Sonderegger, P., Lipkin, L.: Identification of coordinate pairs of polypeptides: A techniques for screening of putative precursor product pairs in 2D gels. Clinical Chemistry 30, 1965-1971, 1984.
21. Lester, E.P., Lemkin, P.F.,: A `GELLAB' computer assisted 2D gel analysis of states of differentiation in hematopoietic cells, In Neuhoff, V. (Ed.): In Electrophoresis '84, 1984. Basel, Switzerland, Springer-Verlag Chemie, pp. 309-311.
22. Sonderegger, P., Lemkin, P., Lipkin, L., Nelson, P., Differential modulation of the expression of axonal proteins by non-neuronal cells and the peripherial and central nervous system, EMBO J. 4, 1395-1401, 1985.
23. Lemkin, P., PSAIL - A portable SAIL compiled translator for C environments. Computer Language 2, 39-45, 1985.
24. Sondregger, P., Lemkin, P.F., Lipkin, L.E., Nelson, P.G., Coordinate regulation of the expression of axonal proteins by the micro-environment, Developmental Biology 118, 222-232, 1986.
25. Lemkin, P., PSAIL: A Portable SAIL to C Compiler - Description and Tutorial, SIGPLAN Notices 23:(10) 149-171, 1988.
26. Stoeckli, E.T., Lemkin, P.F., Kuhn, T.B., Ruegg, M.A., Heller, M., and Sonderegger, P.: Axonally secreted proteins: I. Identification of proteins secreted from axons of embryonic dorsal root ganglia neurons. Eur. J. Biochem 180: 249-258, 1989.
27. Lemkin, P.F., Lester, E.P., Database and Search Techniques for 2D Gel Protein Data: A Comparison of Paradigms For Exploratory Data Analysis and Prospects for Biological Modeling, Electrophoresis, 10(2): 122-140, 1989.
28. Lemkin, P.F., GELLAB-II, A workstation based 2D electrophoresis gel analysis system, in Proceedings of Two-Dimensional Electrophoresis, T. Endler, S. Hanash (Eds), Vienna Austria, Nov 8-11, 1988, VCH Press, W. Germany. 53-57, 1989.
29. Amberger, A., Tontsch, U., Lemkin, P., Gabbiani, G., Bauer, H.C., Two cloned cerebral endothelial cell phenotypes: An in Vitro model for angiogenesis, in Proceedings on Angiogenesis,, 1991.
30. Lemkin, P., Rogan, P., Automatic detection of noisy spots in two-dimensional Southern Blots, App. Theoretical Electrophoresis 2: 141-149, 1991.
31. Lemkin, P., Representations of protein patterns from 2D gel electrophoresis databases, in The Visual Display Of Biological Information, C. Pickover (ed), World Publishers, Teaneck, NJ, 43-59, 1995.
32. Lemkin, P.F., Xconf: a network based conferencing system. Comput Biomed. Res. 76(1) 1-27, 1992.
33. Lemkin, P.F., Myrick, J., Upton, K.: Splitting merged spots in 2D page gel images. Appl. Theor. Electrophoresis, 3:163-172, 1993
34. Lemkin, P.F., Wu, Y., Upton, K.: An efficient disk based data structure for rapid searching of 2D gel databases. Electrophoresis, 14:1341-1350, 1993.
35. Myrick, J.E., Lemkin, P.F., Robinson, M.K., Upton, K.M.: Comparison of the Bio Image VisageTM 2,000 and the GELLAB-II two-dimensional electrophoretic analysis systems. Applied. Theor. Electrophoresis, 3:335-346, 1993.
36. Wu, Y., Lemkin, P.F., Upton, K.: A fast spot segmentation algorithm for 2D electrophoresis analysis. Electrophoresis, 14:1341-1356, 1994 36. Robinson, M.K.,, Myrick, J.E., Henderson, L.O., Coles, C.D., Powell, M.K., Orr, G.A., Lemkin, P.F., Two-dimensional protein electrophoresis and multiple hypothesis testing to detect potential serum protein biomarkers in children with fetal alchol syndrome. Electrophoresis 16(7) 1176-1183, 1995.
O.1 Reiser, J.F. SAIL. Stanford Artificial Intelligence Lab. memo AIM-289, or Computer Science Dept. Report #STAN-CS-76-574, 1976. [Also available as #AD-A045-102 from NTIS, Springfield, VA, 22161]
0.2 Scheifler, R.W., Gettys, J., The X Window System, ACM Transactions on Graphics No. 63, Oct, 1986.
O.3 Feldman, J.A., Rovner, P.D., An Algol-Based Associative Language, CACM 12(8) 439-449,1969.
O.4 Sproull, R., OMNIGRAPH is documented in `DECsystem-10 Omnigraph Display Manual', DCRT, NIH, Bethesda, MD, 1979). [This is also described in an earlier paper: Sproull, R.F., "Omnigraph: simple terminal independent graphics software", Xerox PARC Report CSL-73-4, 1973.]