The Size of the Human Proteome: The Width and Depth.
Elena A. Ponomarenko,Ekaterina V. Poverennaya,Ekaterina V. Ilgisonis,Mikhail A. Pyatnitskiy,Arthur T. Kopylov,Victor G. Zgoda,Andrey Lisitsa,Alexander I. Archakov +7 more
TLDR
In this article, meta-analysis of neXtProt knowledge base is proposed for theoretical prediction of the number of different proteoforms that arise from alternative splicing (AS), single amino acid polymorphisms (SAPs), and posttranslational modifications (PTMs).Abstract:
This work discusses bioinformatics and experimental approaches to explore the human proteome, a constellation of proteins expressed in different tissues and organs. As the human proteome is not a static entity, it seems necessary to estimate the number of different protein species (proteoforms) and measure the number of copies of the same protein in a specific tissue. Here, meta-analysis of neXtProt knowledge base is proposed for theoretical prediction of the number of different proteoforms that arise from alternative splicing (AS), single amino acid polymorphisms (SAPs), and posttranslational modifications (PTMs). Three possible cases are considered: (1) PTMs and SAPs appear exclusively in the canonical sequences of proteins, but not in splice variants; (2) PTMs and SAPs can occur in both proteins encoded by canonical sequences and in splice variants; (3) all modification types (AS, SAP, and PTM) occur as independent events. Experimental validation of proteoforms is limited by the analytical sensitivity of proteomic technology. A bell-shaped distribution histogram was generated for proteins encoded by a single chromosome, with the estimation of copy numbers in plasma, liver, and HepG2 cell line. The proposed metabioinformatics approaches can be used for estimation of the number of different proteoforms for any group of protein-coding genes.read more
Citations
More filters
Journal ArticleDOI
How many human proteoforms are there
Ruedi Aebersold,Jeffrey N. Agar,I. Jonathan Amster,Mark S. Baker,Carolyn R. Bertozzi,Emily S. Boja,Catherine E. Costello,Benjamin F. Cravatt,Catherine Fenselau,Benjamin A. Garcia,Ying Ge,Jeremy Gunawardena,Ronald C. Hendrickson,Paul J. Hergenrother,Christian G. Huber,Alexander R. Ivanov,Ole N. Jensen,Michael C. Jewett,Neil L. Kelleher,Laura L. Kiessling,Nevan J. Krogan,Martin R. Larsen,Joseph A. Loo,Rachel R. Ogorzalek Loo,Emma Lundberg,Emma Lundberg,Michael J. MacCoss,Parag Mallick,Vamsi K. Mootha,Milan Mrksich,Tom W. Muir,Steven M. Patrie,James J. Pesavento,Sharon J. Pitteri,Henry Rodriguez,Alan Saghatelian,Wendy Sandoval,Hartmut Schlüter,Salvatore Sechi,Sarah A. Slavoff,Lloyd M. Smith,Michael Snyder,Paul M. Thomas,Mathias Uhlén,Jennifer E. Van Eyk,Marc Vidal,David R. Walt,Forest M. White,Evan R. Williams,Therese Wohlschlager,Vicki H. Wysocki,Nathan A. Yates,Nicolas L. Young,Bing Zhang +53 more
TL;DR: This work frames central issues regarding determination of protein-level variation and PTMs, including some paradoxes present in the field today, and uses this framework to assess existing data and ask the question, "How many distinct primary structures of proteins (proteoforms) are created from the 20,300 human genes?"
Journal ArticleDOI
Metabolomics for Investigating Physiological and Pathophysiological Processes
TL;DR: How metabolomics is yielding important new insights into a number of important biological and physiological processes is explored, with a major focus on illustrating how metabolomics and discoveries made through metabolomics are improving the understanding of both normal physiology and the pathophysiology of many diseases.
Journal ArticleDOI
Spatial proteomics: a powerful discovery tool for cell biology.
TL;DR: Spatial proteomics improves the understanding of protein function by revealing the subcellular localizations of proteins and their movement between compartments, and ways to improve integration of spatial proteomics data are discussed.
Journal ArticleDOI
Beyond mass spectrometry, the next step in proteomics
Winston Timp,Gregory Timp +1 more
TL;DR: A survey illuminates alternatives for sequencing proteins with the brightest prospects for displacing mass spectrometry and promise to be scalable and seem to be adaptable to bioinformatics tools for calling the sequence of amino acids that constitute a protein.
Journal ArticleDOI
Highly Sensitive and Multiplexed Protein Measurements
Limor Cohen,David R. Walt +1 more
TL;DR: The fundamentals of proteins and protein assays are discussed, including affinity reagents, surface functionalization, assay formats, signal detection, and multiplexing, and the challenges with these methods are discussed.
References
More filters
Journal ArticleDOI
Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase
Randall Keichi Saiki,David H. Gelfand,Susanne Stoffel,Stephen J. Scharf,Russell Higuchi,Glenn Thomas Horn,Kary B. Mullis,Henry A. Erlich +7 more
TL;DR: A thermostable DNA polymerase was used in an in vitro DNA amplification procedure, the polymerase chain reaction, which significantly improves the specificity, yield, sensitivity, and length of products that can be amplified.
Journal ArticleDOI
An integrated map of genetic variation from 1,092 human genomes
Gonçalo R. Abecasis,Adam Auton,Lisa D. Brooks,Mark A. DePristo,Richard Durbin,Robert E. Handsaker,Robert E. Handsaker,Hyun Min Kang,Gabor T. Marth,Gil McVean +9 more
TL;DR: It is shown that evolutionary conservation and coding consequence are key determinants of the strength of purifying selection, that rare-variant load varies substantially across biological pathways, and that each individual contains hundreds of rare non-coding variants at conserved sites, such as motif-disrupting changes in transcription-factor-binding sites.
Journal ArticleDOI
UniProt: the Universal Protein knowledgebase
Rolf Apweiler,Amos Marc Bairoch,Cathy H. Wu,Winona C. Barker,Brigitte Boeckmann,Serenella Ferro,Elisabeth Gasteiger,Hongzhan Huang,Rodrigo Lopez,Michele Magrane,Maria Jesus Martin,Darren A. Natale,Claire O'Donovan,Nicole Redaschi,Lai-Su L. Yeh +14 more
TL;DR: The Swiss-Prot, TrEMBL and PIR protein database activities have united to form the Universal Protein Knowledgebase (UniProt), which is to provide a comprehensive, fully classified, richly and accurately annotated protein sequence knowledgebase, with extensive cross-references and query interfaces.
Journal ArticleDOI
Global quantification of mammalian gene expression control
Björn Schwanhäusser,Dorothea Busse,Na Li,Gunnar Dittmar,Johannes Schuchhardt,Jana Wolf,Wei Chen,Matthias Selbach +7 more
TL;DR: Using a quantitative model, the first genome-scale prediction of synthesis rates of mRNAs and proteins is obtained and it is found that the cellular abundance of proteins is predominantly controlled at the level of translation.
Journal ArticleDOI
The Human Plasma Proteome History, Character, and Diagnostic Prospects
TL;DR: This work speculates on the reasons behind this large discrepancy between the expectations arising from proteomics and the realities of clinical diagnostics and suggests approaches by which protein-disease associations may be more effectively translated into diagnostic tools in the future.
Related Papers (5)
A draft map of the human proteome
Min-Sik Kim,Sneha M. Pinto,Derese Getnet,Raja Sekhar Nirujogi,Srikanth S. Manda,Raghothama Chaerkady,Anil K. Madugundu,Dhanashree S. Kelkar,Ruth Isserlin,Shobhit Jain,Joji Kurian Thomas,Babylakshmi Muthusamy,Pamela Leal-Rojas,Pamela Leal-Rojas,Praveen Kumar,Nandini A. Sahasrabuddhe,Lavanya Balakrishnan,Jayshree Advani,Bijesh George,Santosh Renuse,Lakshmi Dhevi N. Selvan,Arun H. Patil,Vishalakshi Nanjappa,Aneesha Radhakrishnan,Samarjeet Prasad,Tejaswini Subbannayya,Rajesh Raju,Manish Kumar,Sreelakshmi K. Sreenivasamurthy,Arivusudar Marimuthu,Gajanan Sathe,Sandip Chavan,Keshava K. Datta,Yashwanth Subbannayya,Apeksha Sahu,Soujanya D. Yelamanchi,Savita Jayaram,Pavithra Rajagopalan,Jyoti Sharma,Krishna R Murthy,Nazia Syed,Renu Goel,Aafaque Ahmad Khan,Sartaj Ahmad,Gourav Dey,Keshav Mudgal,Aditi Chatterjee,Tai-Chung Huang,Jun Zhong,Xinyan Wu,Patrick G. Shaw,Donald Freed,Muhammad Saddiq Zahari,Kanchan K Mukherjee,Subramanian Shankar,Anita Mahadevan,Henry H N Lam,Chris J. Mitchell,Susarla K. Shankar,Parthasarathy Satishchandra,John T. Schroeder,Ravi Sirdeshmukh,Anirban Maitra,Steven D. Leach,Charles G. Drake,Marc K. Halushka,T. S. Keshava Prasad,Ralph H. Hruban,Candace L. Kerr,Candace L. Kerr,Gary D. Bader,Christine A. Iacobuzio-Donahue,Harsha Gowda,Akhilesh Pandey +73 more
Mass-spectrometry-based draft of the human proteome
Mathias Wilhelm,Judith Schlegl,Hannes Hahne,Amin Moghaddas Gholami,Marcus Lieberenz,Mikhail M. Savitski,Emanuel Ziegler,Lars Butzmann,Siegfried Gessulat,Harald Marx,Toby Mathieson,Simone Lemeer,Karsten Schnatbaum,Ulf Reimer,Holger Wenschuh,Martin Mollenhauer,Julia Slotta-Huspenina,Joos-Hendrik Boese,Marcus Bantscheff,Anja Gerstmair,Franz Faerber,Bernhard Kuster +21 more
Tissue-based map of the human proteome
Mathias Uhlén,Mathias Uhlén,Linn Fagerberg,Björn M. Hallström,Cecilia Lindskog,Per Oksvold,Adil Mardinoglu,Åsa Sivertsson,Caroline Kampf,Evelina Sjöstedt,Evelina Sjöstedt,Anna Asplund,IngMarie Olsson,Karolina Edlund,Emma Lundberg,Sanjay Navani,Cristina Al-Khalili Szigyarto,Jacob Odeberg,Dijana Djureinovic,Jenny Ottosson Takanen,Sophia Hober,Tove Alm,Per-Henrik Edqvist,Holger Berling,Hanna Tegel,Jan Mulder,Johan Rockberg,Peter Nilsson,Jochen M. Schwenk,Marica Hamsten,Kalle von Feilitzen,Mattias Forsberg,Lukas Persson,Fredric Johansson,Martin Zwahlen,Gunnar von Heijne,Jens Nielsen,Jens Nielsen,Fredrik Pontén +38 more