Deep‐Learning‐Assisted Stratification of Amyloid Beta Mutants Using Drying Droplet Patterns
Open Access
- 4 May 2022
- journal article
- research article
- Published by Wiley in Advanced Materials
- Vol. 34 (24), e2110404
- https://doi.org/10.1002/adma.202110404
Abstract
The development of simple and accurate methods to predict mutations in proteins remains an unsolved challenge in modern biochemistry. It is discovered that critical information about primary and secondary peptide structures can be inferred from the stains left behind by their drying droplets. To analyze the complex stain patterns, deep-learning neuronal networks are challenged with polarized light microscopy images derived from the drying droplet deposits of a range of amyloid beta (1-42) (A beta(42)) peptides. These peptides differ in a single amino acid residue and represent hereditary mutants of Alzheimer's disease. Stain patterns are not only reproducible but also result in comprehensive stratification of eight amyloid beta (A beta) variants with predictive accuracies above 99%. Similarly, peptide stains of a range of distinct A beta(42) peptide conformations are identified with accuracies above 99%. The results suggest that a method as simple as drying a droplet of a peptide solution onto a solid surface may serve as an indicator of minute, yet structurally meaningful differences in peptides' primary and secondary structures. Scalable and accurate detection schemes for stratification of conformational and structural protein alterations are critically needed to unravel pathological signatures in many human diseases such as Alzheimer's and Parkinson's disease.Funding Information
- Karlsruhe Institute of Technology
- Helmholtz-Gemeinschaft
This publication has 82 references indexed in Scilit:
- Toxic fibrillar oligomers of amyloid-β have cross-β structureProceedings of the National Academy of Sciences of the United States of America, 2012
- Re‐Shaping the Coffee RingAngewandte Chemie, 2012
- Identification of fluid and substrate chemistry based on automatic pattern recognition of stainsAnalytical Methods, 2011
- Structural conversion of neurotoxic amyloid-β1–42 oligomers to fibrilsNature Structural & Molecular Biology, 2010
- Self-Assembly of Colloidal Particles from Evaporating Droplets: Role of DLVO Interactions and Proposition of a Phase DiagramLangmuir, 2010
- Effects of Familial Alzheimer’s Disease Mutations on the Folding Nucleation of the Amyloid β-ProteinJournal of Molecular Biology, 2008
- Characterizations of distinct amyloidogenic conformations of the Aβ (1–40) and (1–42) peptidesBiochemical and Biophysical Research Communications, 2007
- The 'Arctic' APP mutation (E693G) causes Alzheimer's disease by enhanced Aβ protofibril formationNature Neuroscience, 2001
- Computerised image analysis of biocrystallograms originating from agricultural productsComputers and Electronics in Agriculture, 1999
- A simple method for displaying the hydropathic character of a proteinJournal of Molecular Biology, 1982