Bioinformatics Vol. 18 no. 3 2002
Pages 395-404
© 2002 Oxford University Press
An integrated approach utilizing artificial neural networks and SELDI mass spectrometry for the classification of human tumours and rapid identification of potential biomarkers
1 Department of Life Sciences, Nottingham
Trent University, Clifton Lane, Clifton, Nottingham NG11 8NS, UK
2 Xenova Ltd, 310 Cambridge Science Park,
Milton Road, Cambridge CB4 0WG, UK
3 Department of Neuropathology, Floor A West
Block, Medical School, Queens Medical Centre, Nottingham NG7 2UH,
UK
4 Department of Histopathology, Nottingham
City Hospital, Hucknall Road, Nottingham NG5 1PB, UK
5 Department of Chemistry and Physics,
Nottingham Trent University, Clifton Lane, Clifton, Nottingham NG11
8NS, UK
Received on July 27, 2001
; revised on October 25, 2001
; accepted on November 22, 2001
Motivation: MALDI mass spectrometry is able to elicit macromolecular expression data from cellular material and when used in conjunction with Ciphergen protein chip technology (also referred to as SELDI—Surface Enhanced Laser Desorption/Ionization), it permits a semi-high throughput approach to be taken with respect to sample processing and data acquisition. Due to the large array of data that is generated from a single analysis (8–10000 variables using a mass range of 2–15 kDa—this paper) it is essential to implement the use of algorithms that can detect expression patterns from such large volumes of data correlating to a given biological/pathological phenotype from multiple samples. If successful, the methodology could be extrapolated to larger data sets to enable the identification of validated biomarkers correlating strongly to disease progression. This would not only serve to enable tumours to be classified according to their molecular expression profile but could also focus attention upon a relatively small number of molecules that might warrant further biochemical/molecular characterization to assess their suitability as potential therapeutic targets.
Results: Using a multi-layer perceptron Artificial Neural Network (ANN) (Neuroshell 2) with a back propagation algorithm we have developed a prototype approach that uses a model system (comprising five low and seven high-grade human astrocytomas) to identify mass spectral peaks whose relative intensity values correlate strongly to tumour grade. Analyzing data derived from MALDI mass spectrometry in conjunction with Ciphergen protein chip technology we have used relative importance values, determined from the weights of trained ANNs (Balls et al. , Water, Air Soil Pollut. , 85, 1467–1472, 1996), to identify masses that accurately predict tumour grade. Implementing a three-stage procedure, we have screened a population of approximately 100000–120000 variables and identified two ions (m/zvalues of 13454 and 13457) whose relative intensity pattern was significantly reduced in high-grade astrocytoma. The data from this initial study suggests that application of ANN-based approaches can identify molecular ion patterns which strongly associate with disease grade and that its application to larger cohorts of patient material could potentially facilitate the rapid identification of validated biomarkers having significant clinical (i.e. diagnostic/prognostic) potential for the field of cancer biology.
Availability: Neuroshell 2 is commercially available from ward systems.
Contact: graham.balls{at}ntu.ac.uk
* To whom correspondence should be addressed.
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