1. Volume 25, Issue 1, Pages 5-15 (January 2017)
Structural Analysis of Multi-component Amyloid Systems by Chemometric SAXS Data Decomposition 
Fátima Herranz-Trillo, Minna Groenning, Andreas van Maarschalkerweerd, Romà Tauler, Bente Vestergaard, Pau Bernadó 
Structure 
Volume 25, Issue 1, Pages 5-15 (January 2017)
DOI: /j.str
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2. Structure 2017 25, 5-15DOI: (10.1016/j.str.2016.10.013)
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3. Figure 1 Analysis of the Fibrillation of Insulin
(A) SAXS profiles recorded during the evolution of fibrillation of insulin. Scattering intensity profiles (black dots) in logarithmic scale as a function of the momentum transfer (s = 4π sin(θ)/λ [2θ, scattering angle; λ = 1.5 Å, X-ray wavelength]) measured from t = 0 (bottom curve) to t = 11 hr (top curve). COSMiCS fitted model combining Absolute and Holtzer (AH) data representations with three species are displayed as solid red lines. Curves are translated arbitrarily along the y axis for clarity.
(B) SAXS profiles in logarithmic scale from the decomposition of the insulin dataset using COSMiCS, displaying the monomer (blue), oligomer (green), and fibril (red) curves. Fits of the ab initio reconstructions are displayed as solid lines.
(C) Pairwise distribution functions derived from the individual curves for each species computed with the program GNOM (Svergun, 1992). The same color code as in (B) is used.
(D) Time-dependent concentration profiles derived from COSMiCS for each species with the same color code as in (B) (smoothing of the data in solid lines). The ThT fluorescence signal (black) is included to highlight its excellent correlation with the population of fibrils derived from the COSMiCS analysis.
Structure  , 5-15DOI: ( /j.str )
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4. Figure 2 Structural Models of Insulin Fibrillar Species
Ab initio reconstructions of the three components obtained from the COSMiCS analysis of the SAXS data measured along the insulin fibrillation. Structures of the monomer (blue), oligomer (green), and the repeating unit of the fibril (red) are displayed in their relative sizes. The monomer is displayed in two orientations, one rotated 90°. The oligomer is displayed in more detail in the inset.
Structure  , 5-15DOI: ( /j.str )
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5. Figure 3 α-SNE46K SAXS Data
SAXS profiles showing the evolution of fibrillation of α-SNE46K (black dots) in logarithmic scale as a function of the momentum transfer (s = 4π sin(θ)/λ [2θ, scattering angle; λ = 1.24 Å, X-ray wavelength]). Bottom curve corresponds to the first curve (time = 0 hr) and top curve corresponds to t = 25.6 hr. Red lines are the COSMiCS fits obtained from the three-component mixture using Absolute and Holtzer and Kratky representations (AHK) of the SAXS data. The curve corresponding to t = 25.33 hr has been identified as an outlier and is not used for the global fitting (and hence no COSMiCS fit is superposed). Curves are translated arbitrarily along the y axis for visualization purposes.
Structure  , 5-15DOI: ( /j.str )
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6. Figure 4 Assessment of Outlier Curves in the α-SNE46K SAXS Dataset
(A) Individual χi2 values obtained from the COSMiCS analysis of the α-SNE46K complete dataset using the AKP combination of matrices. One single value appears as a potential outlier (curve 45, marked in red).
(B) The variation in the χi2 values of the individual curves when extracting curve 45 (corresponding to a time of 25.33 hr) from the analysis using the AHK combination. A systematic improvement for the vast majority of curves of the dataset is observed upon extraction of the curve from the global fitting, and it is hence concluded that curve 45 is an outlier.
(C) Difference in individual χi2 values derived from the COSMiCS analysis with the AHK combination using 48 curves of the α-SNE46K dataset and the AKP combination using 47 curves in the dataset after removing the SAXS curve corresponding to t = 25.6 hr from the analysis. Either no effect or an increase in the χi2 values is observed. It can be concluded that the extraction of this second curve does not improve the derived model and it is therefore not justifiable.
Structure  , 5-15DOI: ( /j.str )
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7. Figure 5 COSMiCS Analysis of α-SNE46K Fibrillation
Results from the decomposition of the α-SNE46K data with COSMiCS using the AHK combination of matrices.
(A) Decomposed SAXS profiles for the monomer (blue), oligomer (green), and fibril (red) species.
(B) p(r) functions of the three species computed from the SAXS profiles of (A) using GNOM (Svergun, 1992).
(C) Concentration profiles with the same color code as before and with the ThT fluorescence signal superimposed (solid black line). The ThT profile is in excellent agreement with the population of fibrils.
Structure  , 5-15DOI: ( /j.str )
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