Partial Covariance 2D Mass Spectrometry

Reference number 7618

Sectors: Healthcare

Industries: Healthcare equipment, Medical Technology

Proposed use

Partial covariance 2D mass spectrometry is the first of its kind and has the potential to revolutionise not only the field of proteomics, but bio-molecular mass spectrometry in general. It is not limited to a specific apparatus (e.g. ion trap or TOF), activation technique (e.g. CID, ECD/ETD, etc.) or biomolecular structure (e.g. peptide, protein, oligonucleotide, etc.)

The 2D MS technology produces spectral signatures that are more specific than 1D MS spectra can be, even at theoretical infinite mass precision and resolution and is well suited for structurally challenging molecules such as isomers. The invention is fully compatible with top-down experiments as shown in Figure 3 by using the pC-2DMS software to extract sequence identities of co-fragmented proteins from a single ‘chimera’ 2D map. The fragment-fragment connectivity data uniquely provided by the pC-2DMS are expected to strongly enhance the capability of de novo sequencing in MS.

Problem addressed

1D mass spectrometry (MS) often fails in assigning experimental proteomic MS and tandem MS (MS/MS) data to correct peptide sequences despite its remarkable success in identification and quantification of proteins. Some high biological importance problems, such as identifying mixtures of combinatorially modified peptides, cannot be solved by the state of the art 1D MS.

The partial covariance 2D mass spectrometry (pC-2DMS) for the first time gives access to an entirely new type of structure-specific information: the connectivity between biomolecular fragments detected in tandem MS through covariance correlations between structurally linked pairs. Knowing this connectivity gives a vital advantage for solving the peptide sequence puzzle by piecing the fragments together.

Technology overview

The principle of the covariance 2D mass spectrometry is shown in greater detail in Figure 1, available in the downloadable datasheet. The 2D MS approach provides direct experimental access to fragment-fragment correlations thereby revealing how these fragments originated, even in the case of very low abundance structural signals.

Using our pC-2DMS analysis software suite, biomolecular sequences are identified by matching the experimentally measured fragment-fragment correlations to ‘theoretical’ pairs of fragments, generated by computer simulation based on protein databases and fragmentation rules. This targeted sequence-specific fragment connectivity strategy can therefore reduce ambiguity in peptide identification dramatically.

Benefits

  • Solves structural problems which cannot be solved by the standard 1D MS as a matter of principle. Demonstrated in Figure 2 (see datasheet)
  • Extracts sequence from highly congested spectra of intractable complexity for 1D MS/MS. Demonstrated in Figure 3 (see datasheet)
  • Uncovers “hidden” structurally relevant signals that are below the ad hoc intensity thresholds and have to be disregarded in conventional MS.
  • Implemented as a software to offer a standalone measurement-to-sequence identification package. Fully compatible with commercial MS instrumentation software.
  • Does not require any hardware modifications and can simply be used on a standard mass spectrometer. The technique has been demonstrated using a linear ion trap mass spectrometer.

Intellectual property information

Applied patents: EP3513338A2, US20190206509A1

Contact us about this technology



Contact

Mei Chong

Industry Partnerships and Commercialisation Officer, Natural Sciences

Dr Mei Chong is Industry Partnerships and Commercialisation Officer for the Faculty of Natural Sciences at Imperial College London.

Contact Mei

+44 (0)20 7594 9927

m.chong@imperial.ac.uk

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