Many proteoforms—arising from alternative splicing, post-translational modifications (PTM), 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 and derived an algorithm for optimal inference. We applied this algorithm to infer proteoform stoichiometries in two experimental systems that supported rigorous bench-marking: alkylated proteoforms spiked-in at known ratios and endogenous histone 3 PTM proteoforms quantified relative to internal heavy standards. When compared with the benchmarks, the proteoform stoichiometries interfered by HIquant without using external standards had relative error of 5–15% for simple proteoforms and 20–30% for complex proteoforms. A HIquant server is implemented at: https://web.northeastern.edu/slavov/2014_HIquant/
slavovLab@galos_gann Another problem with such comments is that they can be obfuscated in convolute technical jargon, making them rather hard for professional editors to evaluate. They just make everybody's life harder for no good reason.
slavovLab@rmounce Perhaps the the questions over the credibility of #OA journals are raised my parties having selfish interests to undermine the march of #OA and preserve as long as possible the system that nourishes them.
slavovLab@galos_gann The point of peer review is constructive feedback, not highly-technical comments intended to confuse.
I raise this publicly because I think it's poisonous for the community. It's counterproductive. It's sad. It's pathetic.