Identification of a prognostic signature for old-age mortality by integrating genome-wide transcriptomic data with the conventional predictors: the Vitality 90+ Study.
Identification of a prognostic signature for old-age mortality by integrating genome-wide transcriptomic data with the conventional predictors: the Vitality 90+ Study.
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通过将全基因组的转录组数据与常规预测指标相结合：活力90+研究来鉴定旧年龄死亡率的预后签名。
DOI：
10.1186/1755-8794-7-54
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发表时间：
2014-09-11
影响因子：
2.7
通讯作者：
Hurme M
中科院分区：
文献类型：
--
作者：
Jylhävä J;Raitanen J;Marttila S;Hervonen A;Jylhä M;Hurme M
Prediction models for old-age mortality have generally relied upon conventional markers such as plasma-based factors and biophysiological characteristics. However, it is unknown whether the existing markers are able to provide the most relevant information in terms of old-age survival or whether predictions could be improved through the integration of whole-genome expression profiles. We assessed the predictive abilities of survival models containing only conventional markers, only gene expression data or both types of data together in a Vitality 90+ study cohort consisting of n = 151 nonagenarians. The all-cause death rate was 32.5% (49 of 151 individuals), and the median follow-up time was 2.55 years. Three different feature selection models, the penalized Lasso and Ridge regressions and the C-index boosting algorithm, were used to test the genomic data. The Ridge regression model incorporating both the conventional markers and transcripts outperformed the other models. The multivariate Cox regression model was used to adjust for the conventional mortality prediction markers, i.e., the body mass index, frailty index and cell-free DNA level, revealing that 331 transcripts were independently associated with survival. The final mortality-predicting transcriptomic signature derived from the Ridge regression model was mapped to a network that identified nuclear factor kappa beta (NF-κB) as a central node. Together with the loss of physiological reserves, the transcriptomic predictors centered around NF-κB underscored the role of immunoinflammatory signaling, the control of the DNA damage response and cell cycle, and mitochondrial functions as the key determinants of old-age mortality.
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DOI：
10.1186/2046-2395-2-8
发表时间：
2013-05-02
期刊：
Longevity & healthspan
影响因子：
--
作者：
Baylis D;Bartlett DB;Patel HP;Roberts HC
通讯作者：
Roberts HC
影响因子：
6.3
作者：
Giovannini S;Onder G;Liperoti R;Russo A;Carter C;Capoluongo E;Pahor M;Bernabei R;Landi F
通讯作者：
Landi F
DOI：
10.1073/pnas.1120542109
发表时间：
2012-02-14
影响因子：
11.1
作者：
Gewurz, Benjamin E.;Towfic, Fadi;Kieff, Elliott
通讯作者：
Kieff, Elliott
影响因子：
3.9
作者：
Marttila, Saara;Jylhava, Juulia;Hurme, Mikko
通讯作者：
Hurme, Mikko
影响因子：
4.4
作者：
Kallio MA;Tuimala JT;Hupponen T;Klemelä P;Gentile M;Scheinin I;Koski M;Käki J;Korpelainen EI
通讯作者：
Korpelainen EI