Identification of non-Hodgkin's lymphoma prognosis signatures using the CTGDR method.
BACKGROUND
Although NHL (non-Hodgkin's lymphoma) is the fifth leading cause of cancer incidence and mortality in the USA, it remains poorly understood and is largely incurable. Biomedical studies have shown that genomic variations, measured with SNPs (single nucleotide polymorphisms) in genes, may have independent predictive power for disease-free survival in NHL patients beyond clinical measurements.


RESULTS
We apply the CTGDR (clustering threshold gradient directed regularization) method to genetic association studies using SNPs, analyze data from an association study of NHL and identify prognosis signatures to diffuse large B cell lymphoma (DLBCL) and follicular lymphoma (FL), the two most common subtypes of NHL. With the CTGDR method, we are able to account for the joint effects of multiple genes/SNPs, whereas most existing studies are single-marker based. In addition, we are able to account for the 'gene and SNP-within-gene' hierarchical structure and identify not only predictive genes but also predictive SNPs within identified genes. In contrast, existing studies are limited to either gene or SNP identification, but not both. We propose using resampling methods to evaluate the predictive power and reproducibility of identified genes and SNPs. Simulation study and data analysis suggest satisfactory performance of the CTGDR method.
Ma
Shuangge
S
School of Public Health, Yale University, New Haven, CT 06510, USA. shuangge.ma@yale.edu
Zhang
Yawei
Y
Huang
Jian
J
Han
Xuesong
X
Holford
Theodore
T
Lan
Qing
Q
Rothman
Nathaniel
N
Boyle
Peter
P
Zheng
Tongzhang
T
D000465:Algorithms; D016000:Cluster Analysis; D004252:DNA Mutational Analysis / Q000379:methods*; D004273:DNA, Neoplasm / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000175:diagnosis* / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D015203:Reproducibility of Results; D018570:Risk Assessment / Q000379:methods; D012307:Risk Factors; D012680:Sensitivity and Specificity
D004273:DNA, Neoplasm