Editing Proteomics (section)

==Limitations of genomics and proteomics studies==
Proteomics gives a different level of understanding than genomics for many reasons:
* the level of transcription of a gene gives only a rough estimate of its ''level of translation'' into a protein.<ref name="Gygi1999">{{cite journal | vauthors = Gygi SP, Rochon Y, Franza BR, Aebersold R | title = Correlation between protein and mRNA abundance in yeast | journal = Molecular and Cellular Biology | volume = 19 | issue = 3 | pages = 1720–1730 | date = March 1999 | pmid = 10022859 | pmc = 83965 | doi = 10.1128/MCB.19.3.1720 }}</ref> An [[mRNA]] produced in abundance may be degraded rapidly or translated inefficiently, resulting in a small amount of protein.
* as mentioned above, many proteins experience ''[[post-translational modification]]s'' that profoundly affect their activities; for example, some proteins are not active until they become phosphorylated. Methods such as [[phosphoproteomics]] and [[glycoproteomics]] are used to study post-translational modifications.
* many transcripts give rise to more than one protein, through [[alternative splicing]] or alternative post-translational modifications.
* many proteins form complexes with other proteins or RNA molecules, and only function in the presence of these other molecules.
* protein degradation rate plays an important role in protein content.<ref>{{cite journal | vauthors = Belle A, Tanay A, Bitincka L, Shamir R, O'Shea EK | title = Quantification of protein half-lives in the budding yeast proteome | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 103 | issue = 35 | pages = 13004–13009 | date = August 2006 | pmid = 16916930 | pmc = 1550773 | doi = 10.1073/pnas.0605420103 | doi-access = free | bibcode = 2006PNAS..10313004B }}</ref>

''Reproducibility''. One major factor affecting reproducibility in proteomics experiments is the simultaneous [[elution]] of many more peptides than mass spectrometers can measure. This causes [[stochastic]] differences between experiments due to [[shotgun proteomics|data-dependent acquisition]] of tryptic peptides. Although early large-scale shotgun proteomics analyses showed considerable variability between laboratories,<ref name="Peng2003">{{cite journal | vauthors = Peng J, Elias JE, Thoreen CC, Licklider LJ, Gygi SP | title = Evaluation of multidimensional chromatography coupled with tandem mass spectrometry (LC/LC-MS/MS) for large-scale protein analysis: the yeast proteome | journal = Journal of Proteome Research | volume = 2 | issue = 1 | pages = 43–50 | year = 2003 | pmid = 12643542 | doi = 10.1021/pr025556v | citeseerx = 10.1.1.460.237 }}</ref><ref name="Washburn2001">{{cite journal | vauthors = Washburn MP, Wolters D, Yates JR | title = Large-scale analysis of the yeast proteome by multidimensional protein identification technology | journal = Nature Biotechnology | volume = 19 | issue = 3 | pages = 242–247 | date = March 2001 | pmid = 11231557 | doi = 10.1038/85686 | s2cid = 16796135 }}</ref> presumably due in part to technical and experimental differences between laboratories, reproducibility has been improved in more recent mass spectrometry analysis, particularly on the protein level.<ref>{{cite journal | vauthors = Tabb DL, Vega-Montoto L, Rudnick PA, Variyath AM, Ham AJ, Bunk DM, Kilpatrick LE, Billheimer DD, Blackman RK, Cardasis HL, Carr SA, Clauser KR, Jaffe JD, Kowalski KA, Neubert TA, Regnier FE, Schilling B, Tegeler TJ, Wang M, Wang P, Whiteaker JR, Zimmerman LJ, Fisher SJ, Gibson BW, Kinsinger CR, Mesri M, Rodriguez H, Stein SE, Tempst P, Paulovich AG, Liebler DC, Spiegelman C | display-authors = 6 | title = Repeatability and reproducibility in proteomic identifications by liquid chromatography-tandem mass spectrometry | journal = Journal of Proteome Research | volume = 9 | issue = 2 | pages = 761–776 | date = February 2010 | pmid = 19921851 | pmc = 2818771 | doi = 10.1021/pr9006365 }}</ref> Notably, [[Targeted mass spectrometry|targeted proteomics]] shows increased reproducibility and repeatability compared with shotgun methods, although at the expense of data density and effectiveness.<ref>{{cite journal | vauthors = Domon B, Aebersold R | title = Options and considerations when selecting a quantitative proteomics strategy | journal = Nature Biotechnology | volume = 28 | issue = 7 | pages = 710–721 | date = July 2010 | pmid = 20622845 | doi = 10.1038/nbt.1661 | s2cid = 12367142 }}</ref>

''Data quality''. Proteomic analysis is highly amenable to automation and large data sets are created, which are processed by software algorithms. Filter parameters are used to reduce the number of false hits, but they cannot be completely eliminated. Scientists have expressed the need for awareness that proteomics experiments should adhere to the criteria of analytical chemistry (sufficient data quality, sanity check, validation).<ref>{{cite journal | vauthors = Dupree EJ, Jayathirtha M, Yorkey H, Mihasan M, Petre BA, Darie CC | title = A Critical Review of Bottom-Up Proteomics: The Good, the Bad, and the Future of this Field | journal = Proteomes | volume = 8 | issue = 3 | pages = 14 | date = July 2020 | pmid = 32640657 | pmc = 7564415 | doi = 10.3390/proteomes8030014 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Coorssen JR, Yergey AL | title = Proteomics Is Analytical Chemistry: Fitness-for-Purpose in the Application of Top-Down and Bottom-Up Analyses | journal = Proteomes | volume = 3 | issue = 4 | pages = 440–453 | date = December 2015 | pmid = 28248279 | pmc = 5217385 | doi = 10.3390/proteomes3040440 | doi-access = free }}</ref><ref>{{cite journal | vauthors = König S | title = Spectral quality overrides software score-A brief tutorial on the analysis of peptide fragmentation data for mass spectrometry laymen | journal = Journal of Mass Spectrometry | volume = 56 | issue = 2 | pages = e4616 | date = February 2021 | pmid = 32955142 | doi = 10.1002/jms.4616 | s2cid = 221827335 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Duncan MW | title = Good mass spectrometry and its place in good science | journal = Journal of Mass Spectrometry | volume = 47 | issue = 6 | pages = 795–809 | date = June 2012 | pmid = 22707172 | doi = 10.1002/jms.3038 | bibcode = 2012JMSp...47..795D }}</ref>