Bayesian machine learning improves single-wavelength anomalous diffraction phasing

Garcia-Bonete, Maria-Jose; Katona, Gergely

doi:10.1107/s2053273319011446

Cited by 12 publications

(10 citation statements)

References 48 publications

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“…As demonstrated below, this approach is well justified when the measurement errors in the Bijvoet mates are uncorrelated, but requires some elaboration when they are correlated. As discussed by Garcia-Bonete & Katona (2019), time-dependent effects on the measured intensities, such as radiation damage, can lead to correlations between the errors of mean intensity measurements, and there is evidence of such correlations in some of the data sets that we have examined (discussed below). Correlations in measurement errors can be accounted for by assuming that the errors are drawn from a bivariate normal distribution in which the individual variances are obtained from the data-processing analysis but in which a nonzero correlation is present.…”

Section: Correlated Measurement Errors In Measured Bijvoet Matesmentioning

confidence: 78%

Likelihood-based estimation of substructure content from single-wavelength anomalous diffraction (SAD) intensity data

Hatti

McCoy

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2021

Acta Cryst Sect D Struct Biol

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SAD phasing can be challenging when the signal-to-noise ratio is low. In such cases, having an accurate estimate of the substructure content can determine whether or not the substructure of anomalous scatterer positions can successfully be determined. Here, a likelihood-based target function is proposed to accurately estimate the strength of the anomalous scattering contribution directly from the measured intensities, determining a complex correlation parameter relating the Bijvoet mates as a function of resolution. This gives a novel measure of the intrinsic anomalous signal. The SAD likelihood target function also accounts for correlated errors in the measurement of intensities from Bijvoet mates, which can arise from the effects of radiation damage. When the anomalous signal is assumed to come primarily from a substructure comprising one anomalous scatterer with a known value of f′′ and when the protein composition of the crystal is estimated correctly, the refined complex correlation parameters can be interpreted in terms of the atomic content of the primary anomalous scatterer before the substructure is known. The maximum-likelihood estimation of substructure content was tested on a curated database of 357 SAD cases with useful anomalous signal. The prior estimates of substructure content are highly correlated to the content determined by phasing calculations, with a correlation coefficient (on a log–log basis) of 0.72.

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Section: Correlated Measurement Errors In Measured Bijvoet Matesmentioning

confidence: 78%

Likelihood-based estimation of substructure content from single-wavelength anomalous diffraction (SAD) intensity data

Hatti

McCoy

Read

2021

Acta Cryst Sect D Struct Biol

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“…Only one hub gene (BIRC5) and its corresponding active compound (quercetin) were employed in molecular docking analysis. The PDB code of BIRC5 is “6SHO,” and it can be referred from the previously published study [ 20 ]. The binding energy of quercetin-BIRC5 interaction was -7.5, which indicated that they possessed good binding activity.…”

Section: Resultsmentioning

confidence: 99%

An Integrative Analysis Reveals the Potential Mechanism between Herbal Medicine Yinchen and Immunoregulation in Hepatocellular Carcinoma

Cao

et al. 2020

BioMed Research International

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Aims. Abundant evidences in traditional Chinese medicine (TCM) supported the therapeutic value of herbal medicine Yinchen in hepatocellular carcinoma (HCC), but the underlying mechanism remains to be investigated. Main Methods. The intersection of immune gene set, module genes, HCC-associated genes, and target genes of Yinchen was employed for further analyses. The module genes were identified by weighted gene coexpression network analysis, and the other three gene sets were obtained from public databases. Subsequently, we further explored the clinical value and immunoregulation of the hub gene of intersection. The relevant pathways related to hub gene expression were investigated by gene set enrichment analysis. Finally, the interaction of active compounds and target genes was validated by molecular docking. Key Findings. Thirteen active compounds and 90 target genes of Yinchen were included. After constructing the network among Yinchen, target genes, and HCC, BIRC5 was identified as the hub gene. Significant difference was found between the high-expressed group and the low-expressed group in survival and stage. Different immune subtypes also presented significant difference in BIRC5 expression. Moreover, NK cell and T cell (CD4+ effector memory and CD4+ memory resting) were negatively correlated with BIRC5 expression, while CTLA4 and LAG3 were positively correlated. The results of molecular docking further validated a good binding activity of quercetin-BIRC5 interaction. Significance. In summary, our research identified for the first time a novel underlying association among herbal medicine Yinchen, BIRC5, immunotherapy, and HCC. We speculated that Yinchen may target the immune checkpoints (CTLA4 and LAG3) and activate the immune cells by suppressing BIRC5.

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“…Several other XFEL facilities worldwide are capable of reaching X-ray beam parameters including the tender X-ray energy regime (2-5 keV), providing excellent opportunities for long-wavelength native-SAD phasing of difficult targets. Recent developments, such as the multivariate Bayesian model for estimating anomalous differences (Garcia-Bonete & Katona, 2019) and improvements to the error estimates of XFEL data (Brewster et al, 2019), could potentially improve the SAD phasing of XFEL data further. Moreover, the improved dataanalysis methods implemented in CrystFEL version 0.8.0 and detector-distance optimization protocols can be applied to all types of SFX studies, not only to SAD phasing.…”

Section: Discussionmentioning

confidence: 99%

Advances in long-wavelength native phasing at X-ray free-electron lasers

Nass

Cheng²,

Vera

et al. 2020

Int Union Crystallogr J

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Long-wavelength pulses from the Swiss X-ray free-electron laser (XFEL) have been used for de novo protein structure determination by native single-wavelength anomalous diffraction (native-SAD) phasing of serial femtosecond crystallography (SFX) data. In this work, sensitive anomalous data-quality indicators and model proteins were used to quantify improvements in native-SAD at XFELs such as utilization of longer wavelengths, careful experimental geometry optimization, and better post-refinement and partiality correction. Compared with studies using shorter wavelengths at other XFELs and older software versions, up to one order of magnitude reduction in the required number of indexed images for native-SAD was achieved, hence lowering sample consumption and beam-time requirements significantly. Improved data quality and higher anomalous signal facilitate so-far underutilized de novo structure determination of challenging proteins at XFELs. Improvements presented in this work can be used in other types of SFX experiments that require accurate measurements of weak signals, for example time-resolved studies.

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Bayesian machine learning improves single-wavelength anomalous diffraction phasing

Cited by 12 publications

References 48 publications

Likelihood-based estimation of substructure content from single-wavelength anomalous diffraction (SAD) intensity data

Likelihood-based estimation of substructure content from single-wavelength anomalous diffraction (SAD) intensity data

An Integrative Analysis Reveals the Potential Mechanism between Herbal Medicine Yinchen and Immunoregulation in Hepatocellular Carcinoma

Advances in long-wavelength native phasing at X-ray free-electron lasers

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