Biomarkers in the age of omics: time for a systems biology approach.
Biomarkers in the age of omics: time for a systems biology approach.
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DOI：
10.1089/omi.2010.0023
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发表时间：
2011-03
期刊：
影响因子：
--
通讯作者：
Amri H
中科院分区：
文献类型：
--
作者：
Abu-Asab MS;Chaouchi M;Alesci S;Galli S;Laassri M;Cheema AK;Atouf F;VanMeter J;Amri H
生物标记物发现的限制不仅是技术或生物信息学上的，而且还有概念上的。在我们试图提供解决方案的过程中，我们强调了我们认为限制生物标记物发现进展的三个问题。首先，在没有充分了解病理类型免疫组织化学标记物(IHCM)在临床病理学中应用的特点和局限性的情况下，将病理类型免疫组织化学标记物(IHCM)的概念强加于组学数据造成了混乱。第二，缺乏对疾病异质性范围的认真考虑。第三，生物医学界拒绝向其他生物学科借鉴他们处理异质性的成熟方法。因此，当我们认识到，如果没有先验的数据建模和疾病本身的亚型分类来揭示其异质性的程度，以及其亚型和途径多样性背后的组学克隆像差(驱动因素)，就不能分配和验证组学生物标记物发现方面的真正进展。为了进一步支持我们的观点，我们正在贡献一种新的系统生物学方法，例如简约系统发育方法，用于在生物标记物界定之前的疾病建模。简约系统发育学作为一种在其他生物学学科中成功应用了半个世纪的分析方法，同时实现了几个目标：它在系统发育分类中提供疾病模型，将生物标记物识别为共享的派生表达或突变-同构，基于其异质数据的最简约排列构建标本的组学图谱，并允许将受影响的信号通路的网络图谱作为疾病类别的生物特征。
Limitations to biomarker discovery are not only technical or bioinformatic but conceptual as well. In our attempt to offer a solution, we are highlighting three issues that we think are limiting progress in biomarkers discovery. First, the confusion stemming from the imposition of a pathology-type immunohistochemical marker (IHCM) concept on omics data without fully understanding the characteristics and limitations of IHCMs as applied in clinical pathology. Second, the lack of serious consideration for the scope of disease heterogeneity. Third, the refusal of the biomedical community to borrow from other biological disciplines their well established methods for dealing with heterogeneity. Therefore, real progress in biomarker discovery will be attained when we recognize that an omics biomarker cannot be assigned and validated without a priori data modeling and subtyping of the disease itself to reveal the extent of its heterogeneity, and its omics’ clonal aberrations (drivers) underlying its subtypes and pathways’ diversity. To further support our viewpoints, we are contributing a novel a systems biology method such as parsimony phylogenetic approach for disease modeling prior to biomarker circumscription. As an analytical approach that has been successfully used for a half of a century in other biological disciplines, parsimony phylogenetics simultaneously achieves several objectives: it provides disease modeling in a hierarchical phylogenetic classification, identifies biomarkers as the shared derived expressions or mutations—synapomorphies, constructs the omics profiles of specimens based on the most parsimonious arrangement of their heterogeneous data, and permits network profiling of affected signaling pathways as the biosignature of disease classes.
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DOI：
10.1073/pnas.0607057103
发表时间：
2006-11-28
影响因子：
11.1
作者：
Bielas, Jason H.;Loeb, Keith R.;Loeb, Lawrence A.
通讯作者：
Loeb, Lawrence A.
DOI：
10.1073/pnas.0801523105
发表时间：
2008-09-02
影响因子：
11.1
作者：
Campbell, Peter J.;Pleasance, Erin D.;Stratton, Michael R.
通讯作者：
Stratton, Michael R.
影响因子：
45.3
作者：
Fisher, Bernard;Redmond, Carol K.;Fisher, Edwin R.
通讯作者：
Fisher, Edwin R.
影响因子：
4.6
作者：
AuBuchon, J. P.;de Wildt-Eggen, J.;Dumont, L. J.
通讯作者：
Dumont, L. J.
影响因子：
64.8
作者：
Kolaczkowski, B;Thornton, JW
通讯作者：
Thornton, JW