Reproducibility of SELDI-TOF protein patterns in serum: comparing datasets from different experiments
Reproducibility of SELDI-TOF protein patterns in serum: comparing datasets from different experiments
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DOI：
10.1093/bioinformatics/btg484
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发表时间：
2004-03-22
期刊：
影响因子：
5.8
通讯作者：
Coombes, KR
中科院分区：
文献类型：
--
作者：
Baggerly, KA;Morris, JS;Coombes, KR
动机：人们对使用来自血清的表面增强激光解吸和电离（SELDI）蛋白质质谱的模式来区分患有和非疾病患者的样本非常感兴趣。这种模式的使用没有识别潜在的蛋白质负责。然而，在多次实验中，这一过程的稳定性存在问题。结果：我们比较了同一组3例卵巢癌与正常组织分离实验血清SELDI蛋白组学谱。这些光谱可以在http://clinicalproteomics.steem.com网站上找到。总的来说，结果在不同的实验中是不可重复的。基线校正阻止了两个实验结果的重复。在一个实验中，有证据表明，实验过程中的协议发生了重大变化，这可能会使结果产生偏差。另一方面，光谱噪声区域的结构使我们能够区分正常和癌症，这表明正常和癌症的处理方式不同。在一个实验中被发现具有良好区别的特征集不能推广到其他实验中。最后，三个实验的质量校准都令人怀疑。综上所述，这些和其他的担忧表明，在这些实验中发现的大部分结构可能是由于样品处理的人工产物，而不是癌症的潜在生物学。我们为这些实验的设计和分析提供了一些指导方针，以确保更好的可重复性，生物学上有意义的结果。
Motivation: There has been much interest in using patterns derived from surface-enhanced laser desorption and ionization (SELDI) protein mass spectra from serum to differentiate samples from patients both with and without disease. Such patterns have been used without identification of the underlying proteins responsible. However, there are questions as to the stability of this procedure over multiple experiments.Results: We compared SELDI proteomic spectra from serum from three experiments by the same group on separating ovarian cancer from normal tissue. These spectra are available on the web at http://clinicalproteomics.steem.com. In general, the results were not reproducible across experiments. Baseline correction prevents reproduction of the results for two of the experiments. In one experiment, there is evidence of a major shift in protocol mid-experiment which could bias the results. In another, structure in the noise regions of the spectra allows us to distinguish normal from cancer, suggesting that the normals and cancers were processed differently. Sets of features found to discriminate well in one experiment do not generalize to other experiments. Finally, the mass calibration in all three experiments appears suspect. Taken together, these and other concerns suggest that much of the structure uncovered in these experiments could be due to artifacts of sample processing, not to the underlying biology of cancer. We provide some guidelines for design and analysis in experiments like these to ensure better reproducible, biologically meaningfully results.