title: Combining random forest and 2D correlation analysis to identify serum spectral signatures for neuro-oncology.
abstract: Fourier transform infrared (FTIR) spectroscopy has long been established as an analytical technique for the measurement of vibrational modes of molecular systems. More recently, FTIR has been used for the analysis of biofluids with the aim of becoming a tool to aid diagnosis. For the clinician, this represents a convenient, fast, non-subjective option for the study of biofluids and the diagnosis of disease states. The patient also benefits from this method, as the procedure for the collection of serum is much less invasive and stressful than traditional biopsy. This is especially true of patients in whom brain cancer is suspected. A brain biopsy is very unpleasant for the patient, potentially dangerous and can occasionally be inconclusive. We therefore present a method for the diagnosis of brain cancer from serum samples using FTIR and machine learning techniques. The scope of the study involved 433 patients from whom were collected 9 spectra each in the range 600-4000 cm(-1). To begin the development of the novel method, various pre-processing steps were investigated and ranked in terms of final accuracy of the diagnosis. Random forest machine learning was utilised as a classifier to separate patients into cancer or non-cancer categories based upon the intensities of wavenumbers present in their spectra. Generalised 2D correlational analysis was then employed to further augment the machine learning, and also to establish spectral features important for the distinction between cancer and non-cancer serum samples. Using these methods, sensitivities of up to 92.8% and specificities of up to 91.5% were possible. Furthermore, ratiometrics were also investigated in order to establish any correlations present in the dataset. We show a rapid, computationally light, accurate, statistically robust methodology for the identification of spectral features present in differing disease states. With current advances in IR technology, such as the development of rapid discrete frequency collection, this approach is of importance to enable future clinical translation and enables IR to achieve its potential.
authors.affiliation: WestCHEM, Department of Pure and Applied Chemistry, University of Strathclyde, Thomas Graham Building, 295 Cathedral Street, Glasgow, Scotland G1 1XL, UK. david.palmer@strath.ac.uk and WestCHEM, Department of Pure and Applied Chemistry, University of Strathclyde, Technology and Innovation Centre, 99 George Street, Glasgow G1 1RD, UK. matthew.baker@strath.ac.uk.
authors.forename: Benjamin R
authors.initials: BR
authors.lastname: Smith
authors.affiliation: Neuropathology, Lancashire Teaching Hospitals NHS Trust, Royal Preston Hospital, Sharoe Green Lane, Fulwood, Preston, PR2 9HT, UK.
authors.forename: Katherine M
authors.initials: KM
authors.lastname: Ashton
authors.affiliation: Neurosurgery, The Walton Centre NHS Foundation Trust, Lower Lane, Fazakerley, Liverpool, L9 7LJ, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Brodbelt
authors.affiliation: Neuropathology, Lancashire Teaching Hospitals NHS Trust, Royal Preston Hospital, Sharoe Green Lane, Fulwood, Preston, PR2 9HT, UK.
authors.forename: Timothy
authors.initials: T
authors.lastname: Dawson
authors.affiliation: Neurosurgery, The Walton Centre NHS Foundation Trust, Lower Lane, Fazakerley, Liverpool, L9 7LJ, UK.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Jenkinson
authors.affiliation: SUPA, Department of Physics, University of Strathclyde, 107 Rottenrow East, Glasgow, G4 0NG, UK.
authors.forename: Neil T
authors.initials: NT
authors.lastname: Hunt
authors.affiliation: WestCHEM, Department of Pure and Applied Chemistry, University of Strathclyde, Thomas Graham Building, 295 Cathedral Street, Glasgow, Scotland G1 1XL, UK. david.palmer@strath.ac.uk.
authors.forename: David S
authors.initials: DS
authors.lastname: Palmer
authors.affiliation: WestCHEM, Department of Pure and Applied Chemistry, University of Strathclyde, Technology and Innovation Centre, 99 George Street, Glasgow G1 1RD, UK. matthew.baker@strath.ac.uk.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Baker
mesh_terms: D001706:Biopsy; D001932:Brain Neoplasms / Q000097:blood* / Q000175:diagnosis*; D006801:Humans; D012680:Sensitivity and Specificity; D044967:Serum / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared