Midcor

Midcor performs correction of raw mass spectrometry (MS) spectra from ^13C stable isotope-resolved metabolomics (SIRM) experiments to enable accurate metabolic flux analysis.

Key Features:

• Implementation: Implemented as an R-program for processing raw MS recordings from samples incubated with isotopically enriched substrates.
• Mass spectrum extraction: Extracts mass spectra of metabolites of interest from MS recordings.
• Natural isotope correction: Corrects spectra for natural isotope abundance to distinguish ^13C-labeled metabolites from naturally occurring isotopes.
• Overlap resolution: Resolves overlapping peaks arising from cell culture medium components and derivatized fragments to recover true labeled metabolite spectra.
• Automated decision-making: Compares theoretical and experimentally measured spectra across complete and minimal media and selects correction procedures accordingly.
• Discrepancy handling: If discrepancies (D) between complete and minimal media are observed, D is subtracted from raw spectra; if D is consistent across media, corrections are made proportionally based on known labeling.
• Isotopic effect correction: Adjusts for isotopic effects on peak intensities when a priori labeled spectra are provided.
• Simulation and modeling: Simulates corrected spectra using a kinetic model based on ordinary differential equations (ODEs) to generate dynamic flux maps.

Scientific Applications:

• Metabolic Flux Analysis: Enables accurate correction of MS data to quantify metabolic fluxes from ^13C labeling experiments.
• Biochemical Pathway Mapping: Supports generation of dynamic flux maps to elucidate biochemical reaction networks.
• Isotope Tracing Studies: Improves reliability of stable isotope tracing by correcting for natural isotopes, overlaps, and isotopic effects.

Methodology:

Extract mass spectra from MS recordings; correct for natural isotope abundance; identify and handle overlaps by comparing spectra from complete and minimal media (subtract discrepancies D or apply proportional corrections based on known labeling); optionally correct isotopic effects using a priori labeled spectra; simulate corrected spectra with a kinetic ODE model to produce dynamic flux maps.