Proteome informatics 2.1 Introduction2.2 Manual De novo Sequencing; 2.3 Computer Algorithms; 2.3.1 Search Tree Pruning; 2.3.2 Spectrum Graph; 2.3.3 PEAKS Algorithm; 2.4 Scoring Function; 2.4.1 Likelihood Ratio; 2.4.2 Utilization of Many Ion Types; 2.4.3 Combined Use of Different Fragmentations; 2.4.4 Machine Learning; 2.4.5 Amino Acid Score; 2.5 Computer Software; 2.5.1 Lutefisk; 2.5.2 Sherenga; 2.5.3 PEAKS; 2.5.4 PepNovo; 2.5.5 DACSIM; 2.5.6 NovoHMM; 2.5.7 MSNovo; 2.5.8 PILOT; 2.5.9 pNovo; 2.5.10 Novor; 2.6 Conclusion: Applications and Limitations of De novo Sequencing Bringing together world experts to provide clear explanations of the key algorithms workflows and analysis frameworks Proteome Informatics will provide a detailed introduction to the main informatics topics that underpin the various LC MS MS protocols used for protein identification and quantitation 3.13 Search Results Vary Between Various Database Search Engines and Different Peptide Identification Search Strategies3.14 Conclusion; References; Chapter 4 PSM Scoring and Validation; 4.1 Introduction; 4.2 Statistical Scores and What They Mean; 4.2.1 Statistical Probability p Values and Multiple Testing; 4.2.2 Expectation Scores; 4.2.3 False Discovery Rates; 4.2.4 q Values; 4.2.5 Posterior Error Probability; 4.2.6 Which Statistical Measure to Use and When; 4.2.7 Target Decoy Approaches for FDR Assessment; 4.3 Post Search Validation Tools and Methods; 4.3.1 Qvality; 4.3.2 PeptideProphet 2.6.1 Sequencing Novel Peptides and Detecting Mutated Peptides2.6.2 Assisting Database Search; 2.6.3 De novo Protein Sequencing; 2.6.4 Unspecified PTM Characterization; 2.6.5 Limitations; Acknowledgements; References; Chapter 3 Peptide Spectrum Matching via Database Search and Spectral Library Search; 3.1 Introduction; 3.2 Protein Sequence Databases; 3.3 Overview of Shotgun Proteomics Method; 3.4 Collision Induced Dissociation Fragments Peptides in Predictable Ways; 3.5 Overview of Database Searching; 3.6 MyriMatch Database Search Engine; 3.6.1 Spectrum Preparation 3.6.2 Peptide Harvesting from Database3.6.3 Comparing Experimental MS MS with Candidate Peptide Sequences; 3.7 Accounting for Post Translational Modifications During Database Search; 3.8 Reporting of Database Search Peptide Identifications; 3.9 Spectral Library Search Concept; 3.10 Peptide Spectral Libraries; 3.11 Overview of Spectral Library Searching; 3.12 Pepitome Spectral Library Search Engine; 3.12.1 Experimental MS2 Spectrum Preparation; 3.12.2 Library Spectrum Harvesting and Spectrum Spectrum Matching; 3.12.3 Results Reporting Cover; Proteome Informatics; Acknowledgements; Contents; Chapter 1 Introduction to Proteome Informatics; 1.1 Introduction; 1.2 Principles of LC MS MS Proteomics; 1.2.1 Protein Fundamentals; 1.2.2 Shotgun Proteomics; 1.2.3 Separation of Peptides by Chromatography; 1.2.4 Mass Spectrometry; 1.3 Identification of Peptides and Proteins; 1.4 Protein Quantitation; 1.5 Applications and Downstream Analysis; 1.6 Proteomics Software; 1.6.1 Proteomics Data Standards and Databases; 1.7 Conclusions; Acknowledgements; References; Section I Protein Identification; Chapter 2 De novo Peptide Sequencing