비선형 혼합효과모형에서의 로버스트 능형회귀 방법과 정량적 고속 대량 스크리닝 자료에의 응용 = Robust ridge regression for nonlinear mixed effects models with applications to quantitative high throughput screening assay data

다국어 초록 (Multilingual Abstract)

A nonlinear mixed effects model is mainly used to analyze repeated measurement data in various fields. A nonlinear mixed effects model consists of two stages: the first-stage individual-level model considers intra-individual variation and the second-stage population model considers inter-individual variation. The individual-level model, which is the first stage of the nonlinear mixed effects model, estimates the parameters of the nonlinear regression model. It is the same as the general nonlinear regression model, and usually estimates parameters using the least squares estimation method. However, the least squares estimation method may have a problem that the estimated value of the parameters and standard errors become extremely large if the assumed nonlinear function is not explicitly revealed by the data. In this paper, a new estimation method is proposed to solve this problem by introducing the ridge regression method recently proposed in the nonlinear regression model into the first-stage individual-level model of the nonlinear mixed effects model. The performance of the proposed estimator is compared with the performance with the standard estimator through a simulation study. The proposed methodology is also illustrated using quantitative high throughput screening data obtained from the US National Toxicology Program.

국문 초록 (Abstract)

비선형 혼합효과 모형은 다양한 분야에서 반복 측정 자료를 분석할 때 주로 사용된다. 비선형 혼합효과 모형은 개체 내 변동(intra-individual variation)에 대해 고려하는 제 1단계 개별수준모델(individual-level model)과 개체 간 변동(inter-individual variation)에 대해 고려하는 제 2단계 개체군모델(population model)의 두 단계로 구성되어 있다. 비선형 혼합효과 모형의 첫 번째 단계인 개별수준모델은 비선형 회귀모형의 모수를 추정하는 것으로 일반적인 비선형 회귀모형과 같고, 주로 보통최소제곱추정 방법을 사용하여 모수를 추정한다. 그러나 최소제곱추정방법은 가정된 비선형 함수가 자료에 의해 명시적으로 드러나지 않는 경우 모수의 추정값과 그 표준오차가 극단적으로 커지는 문제가 발생할 수 있다. 본 논문에서는 최근에 비선형 회귀모형에서 제안된 능형회귀(ridge regression) 방법을 비선형 혼합효과 모형의 제 1단계 개별수준모델에 도입함으로써 이러한 문제를 해결할 수 있는 새로운 추정방법을 제안하였다. 제안된 추정량은 모의실험 연구를 통하여 기존의 표준적인 추정량과 그 성능을 비교하였다. 또한 미국의 National Toxicology Program으로부터 얻어진 정량적 대량고속 스크리닝(quantitative high throughput screening) 실제 자료를 사용하여 추정 방법들을 비교하였다.

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