Recognizing and analyzing variability in amyloid formation kinetics: Simulation and statistical methods

被引：8

作者：

Hall, Damien ^{[1
,3
]}

Zhao, Ran ^{[1
]}

So, Masatomo ^{[3
]}

Adachi, Masayuki ^{[3
]}

Rivas, German ^{[2
]}

Carver, John A. ^{[1
]}

Goto, Yuji ^{[3
]}

机构：

[1] Australian Natl Univ, Res Sch Chem, Acton, ACT 2601, Australia

[2] CSIC, Ctr Invest Biol, Madrid 28006, Spain

[3] Osaka Univ, Inst Prot Res, 3-1 Yamada Oka, Suita, Osaka 5650871, Japan

来源：

ANALYTICAL BIOCHEMISTRY | 2016年 / 510卷

基金：

英国医学研究理事会;

关键词：

Amyloid; Aggregation assay; Statistical significance; Anti-amyloid drug screening; TRANSMISSION ELECTRON-MICROSCOPY; ALZHEIMERS-DISEASE; IN-VITRO; AGGREGATION KINETICS; PROTEIN AGGREGATION; FIBRIL FORMATION; NUCLEATION; MECHANISM; MODEL; FIBRILLIZATION;

D O I：

10.1016/j.ab.2016.07.013

中图分类号：

Q5 [生物化学];

学科分类号：

071010 ; 081704 ;

摘要：

We examine the phenomenon of variability in the kinetics of amyloid formation and detail methods for its simulation, identification and analysis. Simulated data, reflecting intrinsic variability, were produced using rate constants, randomly sampled from a pre-defined distribution, as parameters in an irreversible nucleation-growth kinetic model. Simulated kinetic traces were reduced in complexity through description in terms of three characteristic parameters. Practical methods for assessing convergence of the reduced parameter distributions were introduced and a bootstrap procedure was applied to determine convergence for different levels of intrinsic variation. Statistical methods for assessing the significance of shifts in parameter distributions, relating to either change in parameter mean or distribution shape, were tested. Robust methods for analyzing and interpreting kinetic data possessing significant intrinsic variance will allow greater scrutiny of the effects of anti-amyloid compounds in drug trials. Crown Copyright (C) 2016 Published by Elsevier Inc. All rights reserved.

引用

页码：56 / 71

页数：16

共 52 条

[1] Probing the Sources of the Apparent Irreproducibility of Amyloid Formation: Drastic Changes in Kinetics and a Switch in Mechanism Due to Micelle like Oligomer Formation at Critical Concentrations of IAPP [J].