Abstract P-4: Robust Method for Background Subtraction in Serial X-ray Diffraction Data
Background: Membrane receptors play an important role in signal transduction across the cell membrane in all living organisms. Their structural studies have been enabled by multiple technological breakthroughs in their heterologous expression, stabilization, crystallization, and crystallographic dat...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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International Medical Research and Development Corporation
2021-06-01
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| Series: | International Journal of Biomedicine |
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| Online Access: | http://ijbm.org/articles/v11s1/ijbm_2021_11_s1_p4.pdf |
| _version_ | 1818865003465277440 |
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| author | Egor Marin Daniil Vakhrameev Anastasiia Gusach Aleksandra Luginina Kirill Kovalev Wei Liu Uwe Weierstall Jaehun Park Ki Hyun Nam Cho Yunje Alexey Mishin Vadim Cherezov Valentin Borshchevskiy |
| author_facet | Egor Marin Daniil Vakhrameev Anastasiia Gusach Aleksandra Luginina Kirill Kovalev Wei Liu Uwe Weierstall Jaehun Park Ki Hyun Nam Cho Yunje Alexey Mishin Vadim Cherezov Valentin Borshchevskiy |
| author_sort | Egor Marin |
| collection | DOAJ |
| description | Background: Membrane receptors play an important role in signal transduction across the cell membrane in all living organisms. Their structural studies have been enabled by multiple technological breakthroughs in their heterologous expression, stabilization, crystallization, and crystallographic data collection as well as in cryogenic electron microscopy (cryoEM). During the last decade, serial femtosecond crystallography (SFX) using X-ray free electron lasers (XFELs) has enabled structure determination of previously inaccessible proteins, including several G-protein-coupled receptors (GPCR), that produce only micrometer-sized crystals, thus paving the way towards understanding their activation mechanism and rational drug discovery. In addition to experimental difficulties, membrane protein structure determination is also often accompanied by data processing challenges. In particular, the lipidic cubic phase that serves as a carrier for membrane protein microcrystals, as well as various XFEL beam-shaping devices may generate substantial background scattering that could complicate the structure factor extraction from the diffraction images.
Methods: In this work, we tested an adaptation of the denoising algorithm via matrix decomposition to XFEL-SFX data. We benchmarked its performance using high-background data from PAL-XFEL and established its applicability to serial crystallography image denoising, as well as compared it to the CrystFEL-based image denoising algorithm.
Results: We find that, although the decomposition-based image denoising does not outperform CrystFEL median subtraction, it performs better than the integration without any additional subtraction. We find the non-negative matrix factorization performing better than more traditional singular-value decomposition methods, both in terms of visual interpretability and final data quality.
Conclusion: We hope that this work will draw attention to background subtraction methods in structural biology, and will pave the way towards processing of most challenging datasets in structural biology, in particularly, those collected from membrane proteins. |
| first_indexed | 2024-12-19T10:40:38Z |
| format | Article |
| id | doaj.art-841a90d82024427a84f205a4f2d94f81 |
| institution | Directory Open Access Journal |
| issn | 2158-0510 2158-0529 |
| language | English |
| last_indexed | 2024-12-19T10:40:38Z |
| publishDate | 2021-06-01 |
| publisher | International Medical Research and Development Corporation |
| record_format | Article |
| series | International Journal of Biomedicine |
| spelling | doaj.art-841a90d82024427a84f205a4f2d94f812022-12-21T20:25:28ZengInternational Medical Research and Development CorporationInternational Journal of Biomedicine2158-05102158-05292021-06-0111Suppl_1121210.21103/IJBM.11.Suppl_1.P4Abstract P-4: Robust Method for Background Subtraction in Serial X-ray Diffraction DataEgor Marin0Daniil Vakhrameev1Anastasiia Gusach2Aleksandra Luginina3Kirill Kovalev4Wei Liu5Uwe Weierstall6Jaehun Park7Ki Hyun Nam8Cho Yunje9Alexey Mishin10Vadim Cherezov11Valentin Borshchevskiy12Pohang Accelerator Laboratory, POSTECH, Pohang, Republic of KoreaResearch Center for Molecular Mechanisms of Aging and Age-related Diseases, Moscow Institute of Physics and Technology, Dolgoprudny, RussiaResearch Center for Molecular Mechanisms of Aging and Age-related Diseases, Moscow Institute of Physics and Technology, Dolgoprudny, RussiaResearch Center for Molecular Mechanisms of Aging and Age-related Diseases, Moscow Institute of Physics and Technology, Dolgoprudny, RussiaResearch Center for Molecular Mechanisms of Aging and Age-related Diseases, Moscow Institute of Physics and Technology, Dolgoprudny, Russia; Forschungszentrum Julich, Julich, Germany School of Molecular Sciences and Biodesign Center for Applied Structural Discovery, Biodesign Institute, Arizona State University, Tempe, Arizona, USASchool of Molecular Sciences and Biodesign Center for Applied Structural Discovery, Biodesign Institute, Arizona State University, Tempe, Arizona, USAPohang Accelerator Laboratory, POSTECH, Pohang, Republic of KoreaPohang Accelerator Laboratory, POSTECH, Pohang, Republic of KoreaPohang Accelerator Laboratory, POSTECH, Pohang, Republic of KoreaResearch Center for Molecular Mechanisms of Aging and Age-related Diseases, Moscow Institute of Physics and Technology, Dolgoprudny, RussiaResearch Center for Molecular Mechanisms of Aging and Age-related Diseases, Moscow Institute of Physics and Technology, Dolgoprudny, Russia; Bridge Institute, Department of Chemistry, University of Southern California, Los Angeles, California, USAResearch Center for Molecular Mechanisms of Aging and Age-related Diseases, Moscow Institute of Physics and Technology, Dolgoprudny, RussiaBackground: Membrane receptors play an important role in signal transduction across the cell membrane in all living organisms. Their structural studies have been enabled by multiple technological breakthroughs in their heterologous expression, stabilization, crystallization, and crystallographic data collection as well as in cryogenic electron microscopy (cryoEM). During the last decade, serial femtosecond crystallography (SFX) using X-ray free electron lasers (XFELs) has enabled structure determination of previously inaccessible proteins, including several G-protein-coupled receptors (GPCR), that produce only micrometer-sized crystals, thus paving the way towards understanding their activation mechanism and rational drug discovery. In addition to experimental difficulties, membrane protein structure determination is also often accompanied by data processing challenges. In particular, the lipidic cubic phase that serves as a carrier for membrane protein microcrystals, as well as various XFEL beam-shaping devices may generate substantial background scattering that could complicate the structure factor extraction from the diffraction images. Methods: In this work, we tested an adaptation of the denoising algorithm via matrix decomposition to XFEL-SFX data. We benchmarked its performance using high-background data from PAL-XFEL and established its applicability to serial crystallography image denoising, as well as compared it to the CrystFEL-based image denoising algorithm. Results: We find that, although the decomposition-based image denoising does not outperform CrystFEL median subtraction, it performs better than the integration without any additional subtraction. We find the non-negative matrix factorization performing better than more traditional singular-value decomposition methods, both in terms of visual interpretability and final data quality. Conclusion: We hope that this work will draw attention to background subtraction methods in structural biology, and will pave the way towards processing of most challenging datasets in structural biology, in particularly, those collected from membrane proteins.http://ijbm.org/articles/v11s1/ijbm_2021_11_s1_p4.pdfserial crystallographybackground subtractionmembrane proteins |
| spellingShingle | Egor Marin Daniil Vakhrameev Anastasiia Gusach Aleksandra Luginina Kirill Kovalev Wei Liu Uwe Weierstall Jaehun Park Ki Hyun Nam Cho Yunje Alexey Mishin Vadim Cherezov Valentin Borshchevskiy Abstract P-4: Robust Method for Background Subtraction in Serial X-ray Diffraction Data International Journal of Biomedicine serial crystallography background subtraction membrane proteins |
| title | Abstract P-4: Robust Method for Background Subtraction in Serial X-ray Diffraction Data |
| title_full | Abstract P-4: Robust Method for Background Subtraction in Serial X-ray Diffraction Data |
| title_fullStr | Abstract P-4: Robust Method for Background Subtraction in Serial X-ray Diffraction Data |
| title_full_unstemmed | Abstract P-4: Robust Method for Background Subtraction in Serial X-ray Diffraction Data |
| title_short | Abstract P-4: Robust Method for Background Subtraction in Serial X-ray Diffraction Data |
| title_sort | abstract p 4 robust method for background subtraction in serial x ray diffraction data |
| topic | serial crystallography background subtraction membrane proteins |
| url | http://ijbm.org/articles/v11s1/ijbm_2021_11_s1_p4.pdf |
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