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Quantifying homologous proteins and proteoforms

Dmitry Malioutov, Tianchi Chen, Jacob Jaffe, Edoardo Airoldi, Steve Carr, Bogdan Budnik, View ORCID ProfileNikolai Slavov
doi: https://doi.org/10.1101/168765
Dmitry Malioutov
1T. J. Watson IBM Research Center, 1101 Kitchawan Road, Yorktown Heights, NY 10598, USA
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Tianchi Chen
2Department of Bioengineering, Northeastern University, Boston, MA 02115, USA
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Jacob Jaffe
3Proteomics Platform, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
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Edoardo Airoldi
4Department of Statistics, Harvard University, Cambridge, MA 02138, USA
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Steve Carr
3Proteomics Platform, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
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Bogdan Budnik
5FAS Center for Systems Biology, Harvard University, Cambridge, MA 02138, USA
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Nikolai Slavov
2Department of Bioengineering, Northeastern University, Boston, MA 02115, USA
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  • ORCID record for Nikolai Slavov
  • For correspondence: nslavov@alum.mit.edu
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Abstract

Many proteoforms – arising from alternative splicing, post-translational modifications (PTMs), or paralogous genes – have distinct biological functions, such as histone PTM proteoforms. However, their quantification by existing bottom-up mass–spectrometry (MS) methods is undermined by peptide-specific biases. To avoid these biases, we developed and implemented a first-principles model (HIquant) for quantifying proteoform stoichiometries. We characterized when MS data allow inferring proteoform stoichiometries by HIquant, derived an algorithm for optimal inference, and demonstrated experimentally high accuracy in quantifying fractional PTM occupancy without using external standards, even in the challenging case of the histone modification code. A HIquant server is implemented at: https://web.northeastern.edu/slavov/2014_HIquant/

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted July 26, 2017.
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Quantifying homologous proteins and proteoforms
Dmitry Malioutov, Tianchi Chen, Jacob Jaffe, Edoardo Airoldi, Steve Carr, Bogdan Budnik, Nikolai Slavov
bioRxiv 168765; doi: https://doi.org/10.1101/168765
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Quantifying homologous proteins and proteoforms
Dmitry Malioutov, Tianchi Chen, Jacob Jaffe, Edoardo Airoldi, Steve Carr, Bogdan Budnik, Nikolai Slavov
bioRxiv 168765; doi: https://doi.org/10.1101/168765

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