The Chromosome-Centric Human Proteome Project: A Call to ActionAndreas F. R. Huhmer,*,† Aran Paulus,*,‡ LeRoy B. Martin,§ Kevin Millis,∥ Tasha Agreste,∥ Julian Saba,†

Jennie R. Lill,⊥ Steven M. Fischer,# William Dracup,¶ and Paddy Lavery¶

†Thermo Fisher Scientific, Life Science Mass Spectrometry, San Jose, California 95134, United States‡Bio-Rad Laboratories, Life Science Group, San Jose, California 95126-2423, United States§Waters Corporation, Beverly, Massachusetts 01915, United States∥Cambridge Isotope Laboratories, Andover, Massachusetts 01810, United States⊥Genentech Inc., 1 DNA Way, South San Francisco, California 94080, United States#Agilent Technologies, Santa Clara, California 95051, United States¶William Dracup, Nonlinear Dynamics Ltd., Keel House, Newcastle-upon-Tyne, NE1 2JE, England, United Kingdom

ABSTRACT: The grand vision of the human proteome project (HPP) is movingcloser to reality with the recent announcement by HUPO of the creation of the HPPconsortium in charge of the development of a two-part HPP, one focused on thedescription of proteomes of biological samples or related to diseases (B/D-HPP) andthe other dedicated to a systematic description of proteins as gene products encoded inthe human genome (the C-HPP). This new initiative of HUPO seeks to identify andcharacterize at least one representative protein from every gene, create a proteindistribution atlas and a protein pathway or network map. This vision for proteomics canbe the roadmap of biological and clinical research for years to come if it delivers on itspromises. The Industrial Advisory Board (IAB) to HUPO shares the visions of C-HPP. The IAB will support and criticallyaccompany the overall project goals and the definitions of the critical milestones. The member companies are in a uniqueposition to develop hardware and software, reagents and standards, procedures, and workflows to ensure a reliable source of toolsavailable to the proteomics community worldwide. In collaboration with academia, the IAB member companies can and mustdevelop the tools to reach the ambitious project goals. We offer to partner with and challenge the academic groups leading the C-HPP to define both ambitious and obtainable goals and milestones to make the C-HPP a real and trusted resource for futurebiology.

KEYWORDS: Human Proteome Project, Human Proteome Organization, industrial advisory board, large-scale science,quantitative science, Human Genome Project, protein detection, proteome complexity, proteomics funding

■ THE HPP, AN UNCERTAIN START

The Human Proteome Organization (HUPO) was founded onFebruary 9, 2001, just a few days before the initial publicationof the human genome.1 The mission of HUPO is:

To define and promote proteomics through internationalcooperation and collaborations by fostering the developmentof new technologies, techniques and training to betterunderstand human disease.1

The vision of the Human Proteome Project (HPP) alreadyexisted at HUPO’s inception, yet almost a decade passed beforethe announcement of the HPP in Sydney, Australia inSeptember 2010,2,3 which is composed of the Chromosome-centric (C-HPP) and the Biology/Disease-driven HPP (B/D-HPP) and its official launch in Geneva, Switzerland inSeptember 2011. During the decade that preceded thoseannouncements, efforts were focused on creating proteomemaps of individual organs and finding specific protein changesassociated with diseases of major importance.4−6

Some of these efforts were very successful. For example, thefirst draft of the Chinese Human Liver Proteome Project wascompleted in 2009.7 It demonstrated the power of a concerted

effort to understand the complexity of proteomes on an organlevel. At the same time, the resulting large set of data providedmany new insights but revealed the complexity associated withunderstanding the proteome of a human organ. It provided thecommunity with valuable insight on the limitations of currentprotein detection technologies and highlighted the challengesassociated in organizing, standardizing and interpreting high-quality protein data sets.Other efforts that also involved substantial governmental and

industrial resources were less successful. Overly ambitiouspromises to deliver disease-specific biomarkers and therapeutictargets largely did not materialize. While leaving somesupporters of proteomics disappointed or discouraged, suchdisappointments have encouraged others to refocus and searchfor improved ways to succeed. It is also important to realizethat the challenge of proteomics is enormous and much larger

Special Issue: Chromosome-centric Human Proteome Project

Received: October 5, 2012Published: December 21, 2012

Perspective

pubs.acs.org/jpr

© 2012 American Chemical Society 28 dx.doi.org/10.1021/pr300933p | J. Proteome Res. 2013, 12, 28−32

than initial goal of sequencing the human genome. This lead tothe realization that proteomics needed an effective way oforganizing the necessary global resources as well as developinga clear vision of what will constitute “success”.

■ THE C-HPP MISSIONA group of researchers within HUPO have now proposed aninternationally coordinated, systematic chromosome-basedhuman proteome project (C-HPP) as a first phase of thelarger HPP.8 The C-HPP seeks to:

Complete a highly accurate validation of the humanproteome complement that provides a high quality, completereference proteome data set.This includes:

1. Identification and characterization of at least onerepresentative protein with its abundance and majormodifications from every human gene.

2. Creation of a protein distribution atlas of these proteins,including their subcellular localization.

3. A protein pathway and network map representing theinteractome.

The project is also attempting to organize the informationinto a genomic framework, develop a standardized data analysisapproach and quality control, and provide access to thisinformation to everyone.Since the official launch of the HPP in Geneva, the current

gene-centric C-HPP has gained momentum. A full set of the 24human chromosomes have been “adopted” by teams aroundthe world. Teams from Asia and Australia are taking the lion’sshare of the responsibility with 12 chromosomes, followed bythe EU member states (6 chromosomes), and the Americascontributors (6 chromosomes), including one from Brazil,South America.Not everyone in the field has rallied behind the vision of the

C-HPP. Other large-scale proteomics projects not under theumbrella of an official project of the HUPO organization havebeen proposed, funded, and undertaken.9 Those projects arenot incompatible with, but rather complementary to, the C-HPP. Preliminary findings from those studies suggest that thereare, in principle, no obstacles to validating all human proteinsusing current approaches and technologies. Recent efforts toestablish deep coverage of the proteomes of multiple cell lineshave demonstrated that proteomics approaches today have thesame efficiency and coverage as transcriptome measurementsby RNA-sequencing methods.10−13 Indeed, proteins for allgenes in the human genome could be validated relativelyquickly if a suitable supply of highly differentiated cells and abroad range of human tissues in which all of the proteins areexpected to be expressed are investigated.10 With theintegration of these and other rapidly emerging systems-widedata into existing proteomics resources, the initial phase of theC-HPP project could be completed relatively quickly. This willallow the initiative to then focus on the next phase ofidentifying the major alternative spliced variant and singlenucleotide variant for each protein coding gene as well asassociated changes in the 3 major post-translational mod-ifications (phosphoryl-, acetyl-, and glycosyl-).Comprehensive and deep sequencing of all human cells and

tissues is a necessary step for biology as a large-scale science.About 40% of human genes have not been validatedexperimentally. Among the benefits of such an effort wouldbe the valuable insight into how many proteins are actually

expressed in normal cells or tissues and whether current high-throughput proteomics techniques are capable of detectingthose missing proteins. The complexity, dynamic nature, andunknown depth of the human proteome are suspected to beenormous. Estimates are that the human proteome could giverise to about 1 000 000 potential protein forms including basicsequence variants, post-translational modifications, and in vivocleavage products.14 Acquiring this information will requiretools and validated methods that the proteomics community ispoised to deliver.With the benefit of insights that have emerged from

genomics research, leaders in that field are now acknowledgingthat genomics alone is not enough.15 Genome biology needs toprogress to cell biology and physiology with understanding ofthe linkages between genetic perturbations and the dysregula-tion of proteins downstream. Two decades of genomics hasgenerated many potential disease targets and promising leadsthat await validation by proteomics. It makes sense to providegenomic scientists and medical researchers who know how tonavigate the genome with tools to drill down to validatedprotein-level information.Systematically organizing data using a gene-centric approach,

as outlined in the C-HPP, is also a logical consequence of thedivide-and-conquer strategy the proteomics community hasadopted. The strategy is a practical approach to organizing theproject and a method of driving clear responsibilities withstandardized processes. It is not a philosophical capitulation toa gene-centric world view or a commitment to an omics-only,hypothesis-free research perspective.8

We, the IAB of HUPO, see the C-HPP at a critical stage witha number of synergies emerging. New insights are rapidlygained from the early large-scale protein expression studies.Protein detection technology continues to become morepowerful and easier to use. The proteomics community andits industrial partners must recognize the convergence of thesepositive factors and collaborate now to complete the C-HPPand evolve the larger vision of the HPP. The IAB is articulatingits support of the C-HPP in this special issue of Journal ofProteome Research (JPR).Recognizing the complexity of the human proteome, the C-

HPP has set a goal of 10 years for the completion of theproject.16 We think that is an insufficiently ambitious goal thatsupports the perspective of some critics that the C-HPP is anunworthy project. The C-HPP should press on with thesupport of industry and complete a draft of the C-HPP wellwithin the stated goal of 10 years, using bottom-up and top-down proteomics methods as well as antibodies.

■ HPP - BEYOND CATALOGINGThe HPP has been criticized by many as “another catalogingexercise” and stigmatized as a duplication effort of the HumanGenome Project (HGP) that will not significantly contribute tothe pressing need to find new therapeutic treatments ofcommon diseases. In a response to a recent proposal by the USgovernment to focus on omics as part of its blue-print for thebioeconomy,17 it was stated that all omics efforts shouldeffectively be outsourced, suggesting that cataloging efforts areessentially not a worthwhile use of US tax dollars. Funding andscientific resources instead should be shifted toward researchand technical approaches that drive the understanding ofmodular biology and systems biology.18 We think that the C-HPP and the B/D-HPP have a much larger role in theprogression of biological science. HUPO needs to continue to

Journal of Proteome Research Perspective

dx.doi.org/10.1021/pr300933p | J. Proteome Res. 2013, 12, 28−3229

develop and articulate ways in which the C-HPP and the B/D-HPP will affect the larger biomedical research community andbasic biology.19,20 We offer perspectives to the following fourareas of the C-HPP and the B/D-HPP that we think are criticalto its success.

1

Leaders of the HPP have not stated how the HGP and the HPPprojects clearly differ and how the future phases of the HPPprojects will accelerate our basic understanding of the modulararchitecture of organisms and contribute to the basicunderstanding of biology.21 A protein pathway and networkmap representing the interactome has been articulated as partof the C-HPP mission statement, but few details have beendiscussed besides the goal of creating an inventory of suchcircuitry.16 We agree that the mapping of proteins and theirinteractions with other proteins as part of cellular networks isthe basis for a comprehensive picture of the cellular circuitry.19

However, an understanding of the dynamic nature of biologicalsystems requires that proteomics provides temporal and spatialresolved maps of molecular processes. We need to make amovie of cellular events rather than taking random snapshots ofcellular states and static pictures of network connectivity.22

Why not aim to create the “YouTube channel” for modular andsystems biology to capture the dynamics of emerging networkmodules?

2

In our opinion, a completely different set of scientific tools isnecessary to enable systematic studies of functional subunits inhuman and model organisms. In that respect, the current HPPtool set is too narrowly defined and a much larger set ofmethods have to be part of the HPP strategy. For example, theknowledge database as part of the third pillar of the HPP canonly be a first step and the concept has to extend beyond thereference portal for the human proteome. The informaticsaspects of the HPP are largely defined as a massive datacollection and warehousing effort today, and a much clearer andambitious vision has to emerge that has to include the goal ofthe creation and validation of data sets for systems biologystudies.23 Proteomics has the opportunity to establish biologyas a quantitative science and informatics cannot be theafterthought of such an important project, but has to be frontand center to the efforts. Otherwise, the project is in danger ofbeing seriously underfunded in one of the most importantscientific opportunities of the HPP, the quantitative study ofdisease mechanisms and discovery of associated targets fortherapeutic intervention.

3

Proteomics so far has been evolving largely isolated frommainstream biology24 and inclusion of the broader biologycommunity has emerged as the biggest challenge of the HPP. Arecent bibliometric analysis of research activities in the past 20years found that most protein research focuses on thoseproteins known before the human genome was mapped. A shiftin research activity was often spurred by the emergence of toolsto study a particular protein, not by a change in the protein’sperceived importance. The study concluded that high-qualityreadily available research tools are needed for all discoveredproteins to drive research into the unstudied parts of thehuman genome.25 The IAB of HUPO thinks that the HPP iswell positioned to address this problem and HUPO shouldmake this its core challenge and mission moving forward.28

4

A growing number of biologists today utilize the newtechnologies, workflows and resources generated by proteomicsin the past decade. A convergence of traditional protein analysistechniques familiar to biologists with proteomics approaches isevident. The HPP should include those methods as part of ahorizontal integrated layer across the three pillars of technologyand create connections that integrate traditional with emergingprotein detection tools.14 The orthogonal layer of techniquesshould include many traditional biochemical and molecularmethods, such as protein functional assays with protein specificchemical probes, siRNA for post-transcriptional gene silencing,protein activity assays and techniques probing protein structuralchanges. A much broader set of tools integrated withproteomics techniques will be more attractive to the largerbiology community and drive synergies to unlock the completepicture of the proteome and its complexity.The set of proteins expressed in a particular cell or cell type is

known as its proteome and the goals of the HPP should notattempt to be all inclusive. However, the HPP has an integrativerole and needs to take advantage of it. By creating a clear visionon what the HPP is going to deliver beyond a catalog, and bylinking its goals to activities and methods in the biologycommunity, the HPP will take the first step toward trans-forming biology from a descriptive into a quantitative,hypothesis-driven large-scale science.

■ ROLE OF INDUSTRY

History shows that industry has a significant role to play in theevolution and success of large-scale scientific endeavors. Unlikethe HGP where industry became one of the major drivers of theproject, industrial partners of the HPP have so far not taken amore active role in the shaping of the HPP. The HPP needs thesupport and participation of industry, and in turn we, thebiological tools industry, want to be a partner of the HPP.The current HPP mission defines as one of its goals and

outcomes the delivery of publicly available resources whichincludes protein profiling methods, protein specific reagentsand cDNA clones of all human protein-coding genes. We feelthat the academic sector is not particularly well positioned todeliver on those promises, but should rely on the expertise of itsindustrial partners to produce and distribute high-qualityresearch tools, that include instrumentation, software andconsumables.The role of industry also includes the specific responsibility

and involvement in the integration of a set of well-definedcomplementary technology platforms that make proteomictechniques more accessible to biological research.24 If theultimate goal is to make high-throughput protein detection sosimple and inexpensive in the future that it can be routinelydeployed as a universal tool of biology, the industrial partnersrepresented by the HUPO IAB will have to help to develop anddisseminate well-defined approaches, methods, and comple-mentary technologies that make it possible.

■ C-HPP - A CALL TO ACTION

Large-scale science projects require equally large-scaleprocesses, efficient networks of communication, and big-picturemanagement to achieve division of labor and efficiencies ofscale. Other scientific disciplines, such as particle physics andastronomy, are already comfortable with such processes. Thefield of biology is less accustomed to such large-scale science.

Journal of Proteome Research Perspective

dx.doi.org/10.1021/pr300933p | J. Proteome Res. 2013, 12, 28−3230

The C-HPP will require a broad participation and cooperationacross the scientific community, public agencies, industries, andcountries. In all of this, HUPO must take a leadership role,because ultimately, creating the scientific, administrative, andtechnical processes to enable such large-scale science may proveas valuable as the data itself.26

The HPP began in the shadow of the financial crises of 2008.No one would deny that the macro-economic environmenttoday is less advantageous than the easy-money economicbubble enjoyed by the HGP. At the same time, the C-HPP willbenefit from the advances of the digital age, new ways ofcollaborating and sharing data, that previous large-scale scienceprojects could not. Crowd sourcing through rapid and free datasharing is fast becoming accepted as a method to generateknowledge and will accelerate the HPP in ways that wereimpossible and unimaginable a decade ago. By tapping into thenext generation of scientists with preferences for and familiaritywith social media, economics of scales for the C-HPP can beachieved by true division of labor reducing undesired parallelefforts.Public and private funding agencies across the world should

recognize this unique opportunity. They can support theproject either directly through appropriate grants or indirectly,by requesting investigators of existing funding to use standardsrecommended by HUPO and to make their results available tothe C-HPP. Funding agencies should also take the opportunityto establish novel and innovative protein detection technologiesas part of the C-HPP participation. More importantly, fundingagencies need to recognize that participating teams or countrieswill become part of a highly integrated network that strengthenthe regional scientific basis, establish new collaborativenetworks, and further their institutional and national researchagenda.As with most scientific efforts, there is no way to predict with

certainty how greatly the C-HPP will impact the science ofproteins or the field of biology. The same was true of theHuman Genome Project. Today, no one would deny theimpact of the HGP, the power of the genome maps, and thecheap sequencing technologies generated as result of theproject.27 Generating a complete picture of the human genomenot only created a framework for subsequent research, itenabled a new ways of thinking about hypothesis-driven andhypothesis-free science. It forged collaborations betweendisciplines that rarely interacted before. We should not denythe field of proteomics the opportunity to take the achieve-ments of the HGP to the next level by fully supporting thegoals of the C-HPP.

■ AUTHOR INFORMATION

Corresponding Author

*E-mail: andreas.huhmer@thermofisher.com; aranpaulus@sbcglobal.net.

Notes

The authors declare no competing financial interest.

■ ACKNOWLEDGMENTS

We thank David C. Fisher at Thermo Fisher Scientific for thecritical review of the manuscript. Funding was provided by theauthors' respective companies.

■ ABBREVIATIONS

HUPO, Human Proteome Organization; HPP, HumanProteome Project; C-HPP, Chromosome-centric HumanProteome Project; IAB, Industrial Advisory Board

■ REFERENCES(1) HUPO- Mission statement of HUPO- the human proteomeorganization; www.hupo.org.(2) Editorial. The call of the human proteome. Nat. Methods 2010, 7(9), 661.(3) HUPO. A gene-centric human proteome project: HUPO-theHuman Proteome Organization. Mol. Cell. Proteomics 2010, 2, 427−9.(4) Omenn, G. S.; Aebersold, R.; Paik, Y. K. The human plasmaproteome project. Proteomics 2009, 9, 4−6.(5) Hamacher, M.; Hardt, T.; van Hall, A.; Stephan, C.; Marcus, K.;et al. Inside SMP proteomics: six years German Human BrainProteome Project (HBPP) - a summary. Proteomics 2008, 8 (6),1118−28.(6) He, F. Human liver proteome project: plan, progress, andperspectives. Mol. Cell. Proteomics 2005, 4 (12), 1841−8.(7) Sun, A.; Jiang, Y.; Wang, X.; Liu, Q.; Zhong, F.; He, Q.; Guan,W.; Li, H.; Sun, Y.; Shi, L.; Yu, H.; Yang, D.; Xu, Y.; Song, Y.; Tong,W.; Li, D.; Lin, C.; Hao, Y.; Geng, C.; Yun, D.; Zhang, X.; Yuan, X.;Chen, P.; Zhu, Y.; Li, Y.; Liang, S.; Zhao, X.; Liu, S.; He, F. Liverbase:a comprehensive view of human liver biology. J. Proteome Res. 2010, 9(1), 50−8.(8) Paik, Y. K.; Jeong, S. K.; Omenn, G. S.; Uhlen, M.; Hanash, S.;Cho, S. Y.; Lee, H. J.; Na, K.; Choi, E. Y.; Yan, F.; Zhang, F.; Zhang,Y.; Snyder, M.; Cheng, Y.; Chen, R.; Marko-Varga, G.; Deutsch, E. W.;Kim, H.; Kwon, J. Y.; Aebersold, R.; Bairoch, A.; Taylor, A. D.; Kim, K.Y.; Lee, E. Y.; Hochstrasser, D.; Legrain, P.; Hancock, W. S. TheChromosome-Centric Human Proteome Project for catalogingproteins encoded in the genome. Nat. Biotechnol. 2012, 7, 30 (3),221−3.(9) Lamond, A. I.; Uhlen, M.; Horning, S.; Makarov, A.; Robinson,C.V..; Serrano, L.; Hartl, F. U.; Baumeister, W.; Werenskiold, A. K.;Andersen, J. S.; Vorm, O.; Linial, M.; Aebersold, R.; Mann, M.Advancing cell biology through proteomics in space and time(PROSPECTS). Mol. Cell. Proteomics 2012, 11 (3), O112.017731.(10) Geiger, T.; Wehner, A.; Schaab, C.; Cox, J.; Mann, M.Comparative proteomic analysis of eleven common cell lines revealsubiquitous but varying expression of most proteins. Mol. Cell.Proteomics 2012, 11 (3), M111.014050.(11) Lundberg, E.; Jagerberg, L.; Klevebring, D.; Matic, I.; Geiger, T.;Cox, J.; Algenas, C.; Lundeberg, J.; Mann, M.; Uhlen, M. Defining thetranscriptome and proteome in three functionally different human celllines. Mol. Syst. Biol. 2010, 6, 450.(12) Munoz, J.; Low, T. Y.; Kok, Y. J.; Chin, A.; Frese, C. K.; Ding,V.; Choo, A.; Heck, A. J. The quantitative proteomes of human-induced pluripotent stem cells and embryonic stem cells. Mol. Syst.Biol. 2011, 7, 550.(13) Beck, M.; Schmidt, A.; Malmstroem, J.; Claassen, M.; Ori, A.;Szymborska, A.; Herzog, F.; Rinner, O.; Ellenberg, J.; Aebersold, R.The quantitative proteome of a human cell line. Mol. Syst. Biol. 2011,7, 549.(14) Legrain, P.; Aebersold, R.; Archakov, A.; Bairoch, A.; Bala, K.;Beretta, L.; Bergeron, J.; Borchers, C. H.; Corthals, G. L.; Costello, C.E.; Deutsch, E. W.; Domon, B.; Hancock, W.; He, F.; Hochstrasser, D.;Marko-Varga, G.; Salekdeh, G. H.; Sechi, S.; Snyder, M.; Srivastava, S.;Uhlen, M.; Wu, C. H.; Yamamoto, T.; Paik, Y. K.; Omenn, G. S. Thehuman proteome project: current state and future direction. Mol. Cell.Proteomics 2011, 10 (7), M111.009993.(15) Chakravarti, A. Genomics is not enough. Science 2011, 335, 15.(16) Paik, Y. K.; Omenn, G. S.; Uhlen, M.; Hanash, S.; Marko-Varga,G.; Aebersold, R.; Bairoch, A.; Yamamoto, T.; Legrain, P.; Lee, H. J.;Na, K.; Jeong, S. K.; He, F.; Binz, P. A.; Nishimura, T.; Keown, P.;Baker, M. S.; Yoo, J. S.; Garin, J.; Archakov, A.; Bergeron, J.; Salekdeh,G. H.; Hancock, W. S. Standard guidelines for the chromosome-

Journal of Proteome Research Perspective

dx.doi.org/10.1021/pr300933p | J. Proteome Res. 2013, 12, 28−3231

centric human proteome project. J. Proteome Res. 2012, 11 (4), 2005−13.(17) Office of Science and Technology Policy. National BioeconomyBlueprint. Office of Science and Technology Policy, Executive Officeof the President: Washington D.C., 2012; p 48.(18) Editorial. Big ideas and grand challenges. Nat. Biotechnol. 2011,29 (11), 951.(19) Vidal, M.; Chan, D. W.; Gerstein, M.; Mann, M.; Omenn, G. S.;Tagle, D.; Sechi, S. Workshop Participants. The human proteome - ascientific opportunity for transforming diagnostics, therapeutics, andhealthcare. Clin. Proteomics 2012, 9 (1), 6.(20) Hood, L. E.; Omenn, G. S.; Moritz, R. L.; Aebersold, R.;Yamamoto, K.; Amos, M.; Hunter-Cevera, J.; Locascio, L. WorkshopParticipants. New and improved proteomics technologies for under-standing complex biological systems: Addressing a grand challenge inthe life sciences. Proteomics 2012, 12 (18), 2773−83.(21) Hartwell, L. H.; Hopfield, J. J.; Leibler, S.; Murray, A. W. Frommolecular to modular cell biology. Nature 1999, 402, C47−52.(22) Goel, A.; Li, S. S.; Wilkins, M. R. Four-dimensional visualizationand analysis of protein-protein interaction networks. Proteomics 2011,11 (13), 2672−82.(23) Isalan, M. A cell in a computer. Nature 2012, 488, 40−1.(24) Editorial. Mind the technology gap. Nat. Method 2012, 9 (4),311.(25) Edwards, A. M. Too many roads not taken. Nature 2011, 470,163.(26) Collins, F. S.; Morgan, M.; Patrinos, A. The Human GenomeProject: lessons from large-scale biology. Science 2003, 300 (5617),286−90.(27) Lander, E. S. Initial impact of the sequencing of the humangenome. Nature 2011, 470 (7333), 187−97.(28) Menon, R.; Roy, A.; Mukherjee, S.; Belkin, S.; Zhang, Y.;Omenn, G. S. Functional implications of structural predictions foralternative splice proteins expressed in Her2/neu-induced breastcancers. J. Proteome Res. 2011, 10 (12), 5503−11.

Journal of Proteome Research Perspective

dx.doi.org/10.1021/pr300933p | J. Proteome Res. 2013, 12, 28−3232