TY - GEN
T1 - Analysis of mass spectrometry data for serum biomarker discovery
AU - Ressom, Habtom W.
AU - Varghese, Rency S.
AU - Goldman, Lenka
AU - Loffredo, Christopher A.
AU - Abdel-Hamid, Mohamed
AU - Kyselova, Zuzana
AU - Mechref, Yehia
AU - Novotny, Milos
AU - Goldman, Radoslav
PY - 2007/1/1
Y1 - 2007/1/1
N2 - We present a computational framework to analyze MALDI-TOF mass spectrometry data for quantitative comparison of peptides and glycans in serum. In particular, we introduce an algorithm that detects peaks that are differentially abundant in a subgroup of patients. The method is applied to identify candidate biomarkers in serum samples of 203 participants from Egypt; 73 hepatocellular carcinoma (HCC) cases, 52 patients with chronic liver disease (CLD), and 78 healthy individuals. Mass spectra were generated using two experiments: (1) low molecular weight (LMW) enriched serum samples were used for MALDI-TOF quantification of peptides, and (2) glycans were enzymatically released from proteins in serum and permethylated prior to MALDI-TOF quantification. A subset of the participants (35 HCC and 35 CLD cases) was used to select the most useful peaks. The peak selection step is preceded by peak screening, where we eliminated peaks that seem to have association with covariates such as age, gender, and viral infection based on the 78 spectra from healthy individuals. The performance of the selected peaks was evaluated in terms of detecting the disease state of a blinded independent set that comprised of 38 HCC and 17 CLD cases. Further evaluation of the potential clinical utility of the selected candidate peptide and glycan markers is needed.
AB - We present a computational framework to analyze MALDI-TOF mass spectrometry data for quantitative comparison of peptides and glycans in serum. In particular, we introduce an algorithm that detects peaks that are differentially abundant in a subgroup of patients. The method is applied to identify candidate biomarkers in serum samples of 203 participants from Egypt; 73 hepatocellular carcinoma (HCC) cases, 52 patients with chronic liver disease (CLD), and 78 healthy individuals. Mass spectra were generated using two experiments: (1) low molecular weight (LMW) enriched serum samples were used for MALDI-TOF quantification of peptides, and (2) glycans were enzymatically released from proteins in serum and permethylated prior to MALDI-TOF quantification. A subset of the participants (35 HCC and 35 CLD cases) was used to select the most useful peaks. The peak selection step is preceded by peak screening, where we eliminated peaks that seem to have association with covariates such as age, gender, and viral infection based on the 78 spectra from healthy individuals. The performance of the selected peaks was evaluated in terms of detecting the disease state of a blinded independent set that comprised of 38 HCC and 17 CLD cases. Further evaluation of the potential clinical utility of the selected candidate peptide and glycan markers is needed.
UR - http://www.scopus.com/inward/record.url?scp=50849087036&partnerID=8YFLogxK
U2 - 10.1109/LSSA.2007.4400912
DO - 10.1109/LSSA.2007.4400912
M3 - Conference contribution
SN - 9781424418138
T3 - 2007 IEEE/NIH Life Science Systems and Applications Workshop, LISA
SP - 172
EP - 175
BT - 2007 IEEE/NIH Life Science Systems and Applications Workshop, LISA
PB - IEEE Computer Society
T2 - 2007 IEEE/NIH Life Science Systems and Applications Workshop, LISA
Y2 - 8 November 2007 through 9 November 2007
ER -