Enzymatic misrepair of DNA damage induced by ionizing radiation during the G0/G1 phase of the cell cycle produces chromosome aberrations, such as translocations and dicentrics. Chromosome aberrations can cause major disruptions of function, including cell death, mutation and neoplasia. Radiogenic aberrations are important in biodosimetry, carcinogenesis risk estimation, and tumor radiotherapy treatment planning. They are closely related to aberrations used in characterizing specific tumor types and to large-scale genome rearrangements considered in modern comparative genomics. Recent work has shown that radiogenic exchange-type aberrations are often complex, involving interactions between more than two DNA double strand breaks. To characterize and analyze spectra of complex aberrations adequately, computer simulations are needed, and are now commonly used. The pioneering software, developed by a Berkeley/Harvard team, is CAS (chromosome aberration simulator), a package implementing basic biophysical models of aberration formation via Monte Carlo, Markov chain calculations of break misrejoining, taking into account chromosome geometry in an interphase cell nucleus. The CAS open source software has been successfully applied in joint work with many groups worldwide, and broad support among radiation cytogeneticists for the idea of internet bioinformatics has been identified. The proposed project is the following: 1) reengineer CAS to take advantage of experience with earlier versions and recent progress in aberration theory; 2) make CAS more user-friendly as an open source internet resource; and 3), extend CAS in various ways to keep up with current rapid experimental advances, e.g. in aberration detection technology. An interdisciplinary team has been assembled for this project. The grant would ensure that a computer resource important to the radiation cytogenetics community is kept fully current and readily available.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM068423-02
Application #
6773956
Study Section
Radiation Study Section (RAD)
Program Officer
Li, Jerry
Project Start
2003-07-15
Project End
2007-06-30
Budget Start
2004-07-01
Budget End
2005-06-30
Support Year
2
Fiscal Year
2004
Total Cost
$194,200
Indirect Cost
Name
University of California Berkeley
Department
Biostatistics & Other Math Sci
Type
Schools of Arts and Sciences
DUNS #
124726725
City
Berkeley
State
CA
Country
United States
Zip Code
94704
Hua, Xia; Nguyen, Diana; Raghavan, Barath et al. (2007) Random state transitions of knots: a first step towards modeling unknotting by type II topoisomerases. Topol Appl 154:1381-1397
Sachs, Rainer K; Shuryak, Igor; Brenner, David et al. (2007) Second cancers after fractionated radiotherapy: stochastic population dynamics effects. J Theor Biol 249:518-31
Hodgson, David C; Koh, Eng-Siew; Tran, Tu Huan et al. (2007) Individualized estimates of second cancer risks after contemporary radiation therapy for Hodgkin lymphoma. Cancer 110:2576-86
Levy, Dan; Reeder, Christopher; Loucas, Bradford et al. (2007) Interpreting chromosome aberration spectra. J Comput Biol 14:144-55
Levy, Dan; Yoshida, Ruriko; Pachter, Lior (2006) Beyond pairwise distances: neighbor-joining with phylogenetic diversity estimates. Mol Biol Evol 23:491-8
Ponomarev, Artem L; Belli, Mauro; Hahnfeldt, Philip J et al. (2006) A robust procedure for removing background damage in assays of radiation-induced DNA fragment distributions. Radiat Res 166:908-16
Arsuaga, Javier; Vazquez, Mariel; McGuirk, Paul et al. (2005) DNA knots reveal a chiral organization of DNA in phage capsids. Proc Natl Acad Sci U S A 102:9165-9
Plan, Y; Hlatky, L; Hahnfeldt, P et al. (2005) Full-color painting reveals an excess of radiation-induced dicentrics involving homologous chromosomes. Int J Radiat Biol 81:613-20
Vives, Sergi; Loucas, Bradford; Vazquez, Mariel et al. (2005) SCHIP: statistics for chromosome interphase positioning based on interchange data. Bioinformatics 21:3181-2
Sachs, Rainer K; Chan, Michael; Hlatky, Lynn et al. (2005) Modeling intercellular interactions during carcinogenesis. Radiat Res 164:324-31

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