Effect of size and heterogeneity of samples on biomarker discovery: synthetic and real data assessment.
<h4>Motivation</h4>The identification of robust lists of molecular biomarkers related to a disease is a fundamental step for early diagnosis and treatment. However, methodologies for the discovery of biomarkers using microarray data often provide results with limited overlap. These diffe...
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2012
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oai:doaj.org-article:a29daff6dcd743e2be8cde112e3346ea2021-11-18T07:26:10ZEffect of size and heterogeneity of samples on biomarker discovery: synthetic and real data assessment.1932-620310.1371/journal.pone.0032200https://doaj.org/article/a29daff6dcd743e2be8cde112e3346ea2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22403633/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Motivation</h4>The identification of robust lists of molecular biomarkers related to a disease is a fundamental step for early diagnosis and treatment. However, methodologies for the discovery of biomarkers using microarray data often provide results with limited overlap. These differences are imputable to 1) dataset size (few subjects with respect to the number of features); 2) heterogeneity of the disease; 3) heterogeneity of experimental protocols and computational pipelines employed in the analysis. In this paper, we focus on the first two issues and assess, both on simulated (through an in silico regulation network model) and real clinical datasets, the consistency of candidate biomarkers provided by a number of different methods.<h4>Methods</h4>We extensively simulated the effect of heterogeneity characteristic of complex diseases on different sets of microarray data. Heterogeneity was reproduced by simulating both intrinsic variability of the population and the alteration of regulatory mechanisms. Population variability was simulated by modeling evolution of a pool of subjects; then, a subset of them underwent alterations in regulatory mechanisms so as to mimic the disease state.<h4>Results</h4>The simulated data allowed us to outline advantages and drawbacks of different methods across multiple studies and varying number of samples and to evaluate precision of feature selection on a benchmark with known biomarkers. Although comparable classification accuracy was reached by different methods, the use of external cross-validation loops is helpful in finding features with a higher degree of precision and stability. Application to real data confirmed these results.Barbara Di CamilloTiziana SanaviaMatteo MartiniGiuseppe JurmanFrancesco SamboAnnalisa BarlaMargherita SquillarioCesare FurlanelloGianna ToffoloClaudio CobelliPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 3, p e32200 (2012) |
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Medicine R Science Q Barbara Di Camillo Tiziana Sanavia Matteo Martini Giuseppe Jurman Francesco Sambo Annalisa Barla Margherita Squillario Cesare Furlanello Gianna Toffolo Claudio Cobelli Effect of size and heterogeneity of samples on biomarker discovery: synthetic and real data assessment. |
| description |
<h4>Motivation</h4>The identification of robust lists of molecular biomarkers related to a disease is a fundamental step for early diagnosis and treatment. However, methodologies for the discovery of biomarkers using microarray data often provide results with limited overlap. These differences are imputable to 1) dataset size (few subjects with respect to the number of features); 2) heterogeneity of the disease; 3) heterogeneity of experimental protocols and computational pipelines employed in the analysis. In this paper, we focus on the first two issues and assess, both on simulated (through an in silico regulation network model) and real clinical datasets, the consistency of candidate biomarkers provided by a number of different methods.<h4>Methods</h4>We extensively simulated the effect of heterogeneity characteristic of complex diseases on different sets of microarray data. Heterogeneity was reproduced by simulating both intrinsic variability of the population and the alteration of regulatory mechanisms. Population variability was simulated by modeling evolution of a pool of subjects; then, a subset of them underwent alterations in regulatory mechanisms so as to mimic the disease state.<h4>Results</h4>The simulated data allowed us to outline advantages and drawbacks of different methods across multiple studies and varying number of samples and to evaluate precision of feature selection on a benchmark with known biomarkers. Although comparable classification accuracy was reached by different methods, the use of external cross-validation loops is helpful in finding features with a higher degree of precision and stability. Application to real data confirmed these results. |
| format |
article |
| author |
Barbara Di Camillo Tiziana Sanavia Matteo Martini Giuseppe Jurman Francesco Sambo Annalisa Barla Margherita Squillario Cesare Furlanello Gianna Toffolo Claudio Cobelli |
| author_facet |
Barbara Di Camillo Tiziana Sanavia Matteo Martini Giuseppe Jurman Francesco Sambo Annalisa Barla Margherita Squillario Cesare Furlanello Gianna Toffolo Claudio Cobelli |
| author_sort |
Barbara Di Camillo |
| title |
Effect of size and heterogeneity of samples on biomarker discovery: synthetic and real data assessment. |
| title_short |
Effect of size and heterogeneity of samples on biomarker discovery: synthetic and real data assessment. |
| title_full |
Effect of size and heterogeneity of samples on biomarker discovery: synthetic and real data assessment. |
| title_fullStr |
Effect of size and heterogeneity of samples on biomarker discovery: synthetic and real data assessment. |
| title_full_unstemmed |
Effect of size and heterogeneity of samples on biomarker discovery: synthetic and real data assessment. |
| title_sort |
effect of size and heterogeneity of samples on biomarker discovery: synthetic and real data assessment. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2012 |
| url |
https://doaj.org/article/a29daff6dcd743e2be8cde112e3346ea |
| work_keys_str_mv |
AT barbaradicamillo effectofsizeandheterogeneityofsamplesonbiomarkerdiscoverysyntheticandrealdataassessment AT tizianasanavia effectofsizeandheterogeneityofsamplesonbiomarkerdiscoverysyntheticandrealdataassessment AT matteomartini effectofsizeandheterogeneityofsamplesonbiomarkerdiscoverysyntheticandrealdataassessment AT giuseppejurman effectofsizeandheterogeneityofsamplesonbiomarkerdiscoverysyntheticandrealdataassessment AT francescosambo effectofsizeandheterogeneityofsamplesonbiomarkerdiscoverysyntheticandrealdataassessment AT annalisabarla effectofsizeandheterogeneityofsamplesonbiomarkerdiscoverysyntheticandrealdataassessment AT margheritasquillario effectofsizeandheterogeneityofsamplesonbiomarkerdiscoverysyntheticandrealdataassessment AT cesarefurlanello effectofsizeandheterogeneityofsamplesonbiomarkerdiscoverysyntheticandrealdataassessment AT giannatoffolo effectofsizeandheterogeneityofsamplesonbiomarkerdiscoverysyntheticandrealdataassessment AT claudiocobelli effectofsizeandheterogeneityofsamplesonbiomarkerdiscoverysyntheticandrealdataassessment |
| _version_ |
1718423491886186496 |