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Solutions

Easy, consistent report generation

Development researchers spend massive amounts of time assembling data together and creating reports. Analysts want to create consistent and comprehensive reports without time-consuming “arts-and-crafts.”

Protein Metrics Solution: Byologic, Intact Mass, & Byomap – Analysis tools export formated reports that can be saved into an electronic notebook or other data repository, and can be used with regulatory filings.

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MS-vendor neutral solutions

Many mass spec groups have multiple MS instruments, and it’s quite common to find MS instruments from multiple vendors in labs across a pharmaceutical organization. As different vendors offer different software, this situation requires cross-training and maintenance on multiple software platforms and may limit analysis in the analysis they can do on some instruments.

Protein Metrics Solution: Byonic, Byologic, Byomap, and Intact Mass  – Vendor neutral software that analyzes raw data files from the five major MS vendors (Waters, Thermo, Sciex, Bruker, and Agilent) in .raw, .d, .wiff, or .mzML format.

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Peptide mapping of UV and TIC chromatograms

Peptide mapping is used extensively when establishing methods and tracking critical quality attributes. While not an inherently complicated process, reproducibly inspecting peptide maps is resource intensive — particularly in terms of the time it takes an analyst to do things like adjust the chromatogram baselines, organize corresponding chromatogram and MS data, inspect peaks and vary bounds of peak integrations, identify which peptides elutions, and label and annotate peaks. In addition, creating reports often consumes significant resources.

Protein Metrics Solution: Byomap – Advanced tool for automated peptide mapping and quantitative comparison of sets of samples.

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Detailed PTM analysis

Post translation modification (PTM) analysis is common in protein therapeutics and occurs throughout the development process, from clone selection, to method development, to stress testing, to comparability studies. These modifications can include Oxidation, Deamidation, Glycosylation, Glycation, Truncation and Extension, as well as a battery of additional sample preparation-related modifications. Consequently, accurately quantifying these modifications is critical for both internal development and for reporting to regulatory agencies.

Protein Metrics Solution: Byologic – Inspection and Quantification Software for Therapeutic Proteins.

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Sequence variant analysis

Sequence variants, or single amino acid substitutions, may occur from mutations or mistranslations in the host cell line. Even trace amounts can have an impact on efficacy, immunogenicity, or comparability of product. While identifying sequence variants is do-able with various proteomics search engines, the real challenge with sequence variant analysis is how to distinguish the relatively rare true sequence variants from false positives.

Protein Metrics Solution for SVA Identification: Byonic – The most flexible and sensitive proteomics search engine.

Protein Metrics Solution for SVA Inspection and Reporting: Byologic – Inspection and Quantification Software for Therapeutic Proteins.

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Small, unannotated peaks

Inevitably, there are small ions that elute that are not annotated even in a comprehensive peptide map. It can be cumbersome to step through a data file and analyze and report out these non-annotated peaks.

Protein Metrics Solution: Byomap – Feature finder to report out small, unannotated features in a sample.

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Quantitative comparison of peptide maps

Comparing peptide maps is often a tedious process. Chromatograms collected over time show drift in the elution time of specific peaks, forcing analysts to spend exhaustive effort at aligning peaks. In addition, analysts need to report on the relative area and want to quickly report if key peaks or Critical Quality Attributes are out of tolerance. Comparing peptide maps can be an invaluable tool to process chemists and to development researchers.

Protein Metrics Solution: Byomap – Advanced tool for automated peptide mapping and quantitative comparison of sets of samples.

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Quantitative comparison of released glycans

Comparing released glycan UV chromatograms can be as tedious as comparing peptide maps. Chromatograms collected over time show drift in the elution time of specific peaks, forcing analysts to spend exhaustive effort at aligning peaks. In addition, analysts need to report on the relative area and want to quickly report if key peaks are out of tolerance. Comparing released glycan profiles can be an invaluable tool to development researchers.

Protein Metrics Solution: Byomap – Advanced tool for automated peptide mapping and quantitative comparison of sets of samples.

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Disulfide bond analysis

Whether working on monoclonal antibodies or other therapeutic proteins, analysis of cross-links and disulfide bond is critical to verify the integrity of a sample. Identification and analysis of unexpected bonds and disulfide bond scrambling can be exceptionally laborious.

Protein Metrics Solution: Byonic -> Byologic – for identification, inspection and quantification of disulfide bonds.

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Fragmentation coverage mapping

Whether trying to confirm each amino acid residue in a protein sample or simply trying to see the quality and depth of fragmentation in a set of samples, it can be valuable to review all the identified fragmentation.

Protein Metrics Solution: Byologic – Inspection and Quantification Software for Therapeutic Proteins.
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Host cell protein analysis

In comparing samples, batches, or processes, it may be appropriate to analyze and compare host cell proteins.

Protein Metrics Solution: Byonic – The most flexible and sensitive proteomics search engine.
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Glyco- proteins and peptides identification

N-linked glycosylation may be the most common, and is certainly the most complex, of all posttranslational modifications of proteins. It is also one of the most difficult to study, due to its extreme complexity and the weaker ionization and fragmentation of glycopeptides relative to ordinary peptides. In comparison, O-linked glycosylation presents more analytical problems than almost any other post-translational modification.

Protein Metrics Solution: Byonic – Byonic identifies glycopeptides to the level of peptide sequence and glycan composition.

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See the joint publication with Albert Heck’s lab.  “Extended O‑GlcNAc on HLA Class-I-Bound Peptides”  http://www.ncbi.nlm.nih.gov/pubmed/26280087

 

Unknown or unexpected modifications

Sometimes there are unknown modifications present in a sample. Manual analysis may not reveal these at all.

Protein Metrics Solution: Byonic – Byonic Wildcard Search.
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Consulting and other applications

Protein Metrics provides consulting and custom software solutions for pharmaceutical companies working with therapeutic proteins. We improve reliability and workflow efficiency for protein analysis, from R&D to large-scale production. Contact us to learn how we can help with difficult analytical chemistry problems including:

  • Sequence variants and other protein modifications
  • De novo sequencing
  • Glycosylation analysis
  • Other…

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