TY - JOUR
T1 - Real-space analysis of radiation-induced specific changes with independent component analysis
AU - Borek, Dominika
AU - Bromberg, Raquel
AU - Hattne, Johan
AU - Otwinowski, Zbyszek
N1 - Funding Information:
The authors are indebted to the 19ID and 19BM beamline staff: Randy Alkire, Marianne Cuff, Norma Duke, Steve Ginell, Youngchang Kim, Jerzy Osipiuk and Frank Rotella for their help in the data collection and analysis. We thank Zbigniew Dauter from the Center for Cancer Research, National Cancer Institute, NIH, for providing the data sets for thaumatin used in this analysis. Use of the Argonne National Laboratory Structural Biology Center beamlines at the Advanced Photon Source was supported by the US Department of Energy, Office of Biological and Environmental Research, under Contract No. DE-AC02-11357. We would also like to thank our anonymous referees.
Funding Information:
Funding for this research was provided by: the National Institutes of Health (grant Nos. R01GM053163, R01GM117080 and R01GM118619).
Funding Information:
For this research was provided by: the National Institutes of Health (grant Nos. R01GM053163, R01GM117080 and R01GM118619)
Publisher Copyright:
© International Union of Crystallography, 2018.
PY - 2018/3
Y1 - 2018/3
N2 - A method of analysis is presented that allows for the separation of specific radiation-induced changes into distinct components in real space. The method relies on independent component analysis (ICA) and can be effectively applied to electron density maps and other types of maps, provided that they can be represented as sets of numbers on a grid. Here, for glucose isomerase crystals, ICA was used in a proof-of-concept analysis to separate temperature-dependent and temperature-independent components of specific radiation-induced changes for data sets acquired from multiple crystals across multiple temperatures. ICA identified two components, with the temperature-independent component being responsible for the majority of specific radiation-induced changes at temperatures below 130K. The patterns of specific temperature-independent radiation-induced changes suggest a contribution from the tunnelling of electron holes as a possible explanation. In the second case, where a group of 22 data sets was collected on a single thaumatin crystal, ICA was used in another type of analysis to separate specific radiation-induced effects happening on different exposure-level scales. Here, ICA identified two components of specific radiation-induced changes that likely result from radiation-induced chemical reactions progressing with different rates at different locations in the structure. In addition, ICA unexpectedly identified the radiation-damage state corresponding to reduced disulfide bridges rather than the zero-dose extrapolated state as the highest contrast structure. The application of ICA to the analysis of specific radiation-induced changes in real space and the data pre-processing for ICA that relies on singular value decomposition, which was used previously in data space to validate a two-component physical model of X-ray radiation-induced changes, are discussed in detail. This work lays a foundation for a better understanding of protein-specific radiation chemistries and provides a framework for analysing effects of specific radiation damage in crystallographic and cryo-EM experiments.The signal representing specific X-ray radiation-induced changes in crystals can be separated into distinct and statistically independent components by the independent component analysis method performed in real space. These components can be of native or difference electron density map types and can be interpreted in terms of physical processes and chemical and/or biological reactions.
AB - A method of analysis is presented that allows for the separation of specific radiation-induced changes into distinct components in real space. The method relies on independent component analysis (ICA) and can be effectively applied to electron density maps and other types of maps, provided that they can be represented as sets of numbers on a grid. Here, for glucose isomerase crystals, ICA was used in a proof-of-concept analysis to separate temperature-dependent and temperature-independent components of specific radiation-induced changes for data sets acquired from multiple crystals across multiple temperatures. ICA identified two components, with the temperature-independent component being responsible for the majority of specific radiation-induced changes at temperatures below 130K. The patterns of specific temperature-independent radiation-induced changes suggest a contribution from the tunnelling of electron holes as a possible explanation. In the second case, where a group of 22 data sets was collected on a single thaumatin crystal, ICA was used in another type of analysis to separate specific radiation-induced effects happening on different exposure-level scales. Here, ICA identified two components of specific radiation-induced changes that likely result from radiation-induced chemical reactions progressing with different rates at different locations in the structure. In addition, ICA unexpectedly identified the radiation-damage state corresponding to reduced disulfide bridges rather than the zero-dose extrapolated state as the highest contrast structure. The application of ICA to the analysis of specific radiation-induced changes in real space and the data pre-processing for ICA that relies on singular value decomposition, which was used previously in data space to validate a two-component physical model of X-ray radiation-induced changes, are discussed in detail. This work lays a foundation for a better understanding of protein-specific radiation chemistries and provides a framework for analysing effects of specific radiation damage in crystallographic and cryo-EM experiments.The signal representing specific X-ray radiation-induced changes in crystals can be separated into distinct and statistically independent components by the independent component analysis method performed in real space. These components can be of native or difference electron density map types and can be interpreted in terms of physical processes and chemical and/or biological reactions.
KW - independent component analysis (ICA)
KW - radiation damage
KW - singular value decomposition (SVD)
KW - tunnelling
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U2 - 10.1107/S1600577517018148
DO - 10.1107/S1600577517018148
M3 - Article
C2 - 29488925
AN - SCOPUS:85042688232
SN - 0909-0495
VL - 25
SP - 451
EP - 467
JO - Journal of Synchrotron Radiation
JF - Journal of Synchrotron Radiation
IS - 2
ER -