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Chromosome Aberration Simulator (CAS): Accessing & User's Guide
- Download CAS (zip file, 98kb; 1/15/1999)
- Windows version available online, with source code, executable (Dialogue.exe), and user's guide (Cas.doc). Fortran source files for various versions of CAS, including UNIX versions, are available upon request from Sachs.
CAS User's Guide (html)
- Summary. This software simulates chromosomal rearrangements produced by ionizing radiation during the G0/G1 phase of the cell cycle. It gives a cell-by-cell record of simulated rearrangements, much as in an actual experiment. Simulated relative frequencies and simulated dose-response curves for various types of aberrations can also be obtained. The simulations establish baseline randomness predictions, thereby suggesting a systematic way to organize the data of any particular experiment.
The program uses the classic (i.e., random breakage and reunion) radiation aberration model, modified to incorporate proximity effects. All rearrangements are assumed complete, leaving no unrejoined ends. The model is implemented via Monte-Carlo simulations (Chen et al. 1997). Scoring appropriate for conventional staining, or for fluorescent in situ hybridization (FISH) experiments involving whole-chromosome painting with additional colors, is included. Aberrations are divided into different types according to the classification schemes of Savage (1976), S&S (Savage and Simpson 1994), PAINT (Tucker et al. 1995), or Chen et al. (1996). Chromosome arm lengths for human or non-human genomes can be systematically taken into account by extending to FISH scoring and to complex aberrations methods which are standard (Savage and Papworth 1982, Lucas et al. 1992, Hlatky et al. 1992) for dicentrics and rings.
- Input. In order to perform simulations, the user specifies the following:
- the number of chromosomes;
- if known, the relative lengths of the chromosomes, and their centromere locations;
- the chromosome staining/painting system being simulated;
- the average number of reactive double strand breaks per cell per unit dose (related to the sensitivity of the cells);
- the number of interaction sites in one cell (an integer related to the magnitude of proximity effects).
The last two numbers (4 & 5) must be adjusted to the experiment being simulated. Their values are obtained either from the literature, or by trial and error using the program itself and comparing simulated to experimental frequencies. Thereafter per-cell frequencies for all kinds of simple or complex aberrations can be simulated.
- Output. For conventional staining, or for one FISH color and one counterstain, or for two FISH colors and one counterstain, the software tabulates simulated frequencies for certain aberration types, e.g. dicentrics, centric rings, two-color translocations, insertions, 3-way interchanges, etc. Typically a million cells can be simulated. For any FISH experiment, with any number of colors, an additional "details" file contains cell-by-cell records of visibly rearranged chromosomes up to the first 1,000 cells. If more cells are needed the simulation can be repeated. Various quantities of interest can be estimated by using these cell-by-cell data. Examples include: frequencies for those aberration types whose frequency is not computed automatically; or the average number of color junctions per cell; or the fraction of cell genomes which are unstable (i.e. non-transmissible, i.e. have damage putatively fatal at mitosis (Savage, 1995)); etc. Users can get such additional results automatically if they modify the source code slightly. The simulations can include doses other than the doses used in the actual experiment; they can also include extra information not available in an experiment but implied by the model and its parameters (e.g., in a FISH experiment, the total frequency of dicentrics, painted or not, in the whole genome).
Detailed cell-by-cell information is restricted to 1,000 cells per run, but summary information on aberration frequencies can utilize much larger numbers of simulated cells. Calculation time depends on the cell number, average number of reactive DSBs and platform. In our hands, calculations with a Pentium PC take less than a minute for 1,000 cells and take 10 minutes - 1 hour for 1,000,000 cells (and take even more time when the number of reactive DSBs is unusually large).
- Acknowledgments. This software is a test version prepared by A.M. Chen, P. Hahnfeldt, L. Hlatky, and R.K. Sachs at UC Berkeley and Harvard. Funds for adding interfaces for Windows 95 were supplied by NIH grant CA 63897; upgrades funded by NSF grants DMS 9532055 and BIR 963-0735. The assistance of V. Kaganskiy, J. Lucas and D. Brenner is gratefully acknowledged.
- Authorization. The software is freely available to all non-commercial users. Users must check that it works for their purposes. Permission to use, copy, modify, and distribute this software and its documentation for any non-profit purpose, without fee and without written agreement, is hereby granted, provided that this paragraph and the preceding one appear in all copies. In no event shall the authors be liable to any party for direct, indirect, special, incidental, or consequential damages arising out of the use of this software and its documentation. We specifically disclaim any warranties, including, but not limited to, implied warranties of merchantability and fitness for a particular purpose. The software is on an "as is" basis, and we have no obligation to provide maintenance, support, updates, enhancements, or modifications.
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