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2017 ; 5
(ä): 9
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Application of penalized linear regression methods to the selection of
environmental enteropathy biomarkers
#MMPMID28293424
Lu M
; Zhou J
; Naylor C
; Kirkpatrick BD
; Haque R
; Petri WA Jr
; Ma JZ
Biomark Res
2017[]; 5
(ä): 9
PMID28293424
show ga
BACKGROUND: Environmental Enteropathy (EE) is a subclinical condition caused by
constant fecal-oral contamination and resulting in blunting of intestinal villi
and intestinal inflammation. Of primary interest in the clinical research is to
evaluate the association between non-invasive EE biomarkers and malnutrition in a
cohort of Bangladeshi children. The challenges are that the number of
biomarkers/covariates is relatively large, and some of them are highly
correlated. METHODS: Many variable selection methods are available in the
literature, but which are most appropriate for EE biomarker selection remains
unclear. In this study, different variable selection approaches were applied and
the performance of these methods was assessed numerically through simulation
studies, assuming the correlations among covariates were similar to those in the
Bangladesh cohort. The suggested methods from simulations were applied to the
Bangladesh cohort to select the most relevant biomarkers for the growth response,
and bootstrapping methods were used to evaluate the consistency of selection
results. RESULTS: Through simulation studies, SCAD (Smoothly Clipped Absolute
Deviation), Adaptive LASSO (Least Absolute Shrinkage and Selection Operator) and
MCP (Minimax Concave Penalty) are the suggested variable selection methods,
compared to traditional stepwise regression method. In the Bangladesh data,
predictors such as mother weight, height-for-age z-score (HAZ) at week 18, and
inflammation markers (Myeloperoxidase (MPO) at week 12 and soluable CD14 at week
18) are informative biomarkers associated with children's growth. CONCLUSIONS:
Penalized linear regression methods are plausible alternatives to traditional
variable selection methods, and the suggested methods are applicable to other
biomedical studies. The selected early-stage biomarkers offer a potential
explanation for the burden of malnutrition problems in low-income countries,
allow early identification of infants at risk, and suggest pathways for
intervention. TRIAL REGISTRATION: This study was retrospectively registered with
ClinicalTrials.gov, number NCT01375647, on June 3, 2011.