The DOI matches its Crossref record; 41 of the 41 references it cites were found in a registry or an index.
The BioPlex Network: A Systematic Exploration of the Human Interactome
Open accessAbstract
Protein interactions form a network whose structure drives cellular function and whose organization informs biological inquiry. Using high-throughput affinity-purification mass spectrometry, we identify interacting partners for 2,594 human proteins in HEK293T cells. The resulting network (BioPlex) contains 23,744 interactions among 7,668 proteins with 86% previously undocumented. BioPlex accurately depicts known complexes, attaining 80%-100% coverage for most CORUM complexes. The network readily subdivides into communities that correspond to complexes or clusters of functionally related proteins. More generally, network architecture reflects cellular localization, biological process, and molecular function, enabling functional characterization of thousands of proteins. Network structure also reveals associations among thousands of protein domains, suggesting a basis for examining structurally related proteins. Finally, BioPlex, in combination with other approaches, can be used to reveal interactions of biological or clinical significance. For example, mutations in the membrane protein VAPB implicated in familial amyotrophic lateral sclerosis perturb a defined community of interactors.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“It comprises two sub-assemblies: Retriever composed of VPS35L, VPS26C, and VPS29; and the CCC complex which contains twelve subunits: COMMD1-COMMD10 and the coiled-coil domain-containing (CCDC) proteins CCDC22 and CCDC93.”
From Structure of the endosomal Commander complex linked to Ritscher-Schinzel syndrome (2023) · cites this paper as [19]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“The CCC complex comprises twelve components, the coiled coil domain-containing proteins CCDC22 and CCDC93 and ten COMMD (copper metabolism MURR1 [Mouse U2af1-rs1 region 1) domain) family members COMMD1-COMMD10.2,16,17,18,19”
From Structure of the endosomal Commander complex linked to Ritscher-Schinzel syndrome (2023) · cites this paper as [19]
Experimental — accuracy not yet measuredIn the citing paper
“The community detection approach was well illustrated in recent analyses of protein-protein interaction networks in yeast (Dutkowski et al., 2013) and human (Huttlin et al., 2015).”
From Mapping the multiscale structure of biological systems (2021) · cites this paper as Huttlin et al., 2015
In the citing paper
“In the human study, the authors first performed clique percolation to determine high-level protein communities; subsequently, they ran modularity-based clustering to further subdivide these communities into more granular subsystems, resulting in a multi-layer hierarchical structure (Figure 3A).”
From Mapping the multiscale structure of biological systems (2021) · cites this paper as Huttlin et al., 2015
In the citing paper
“several high throughput studies using robust affinity purification-mass spectrometry methodologies to elucidate protein interaction networks have revealed the interaction of ABCD1 with AT2B2 [ 167 ] and ABCD3 with AT2B2 and AT2A2 [ 168 , 169 ]”
From Peroxisomal ABC Transporters: An Update (2021) · cites this paper as [169]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing
Benjamini, Y., & Hochberg, Y. (1995) · Journal of the Royal Statistical Society Series B: Statistical Methodology · doi:10.1111/j.2517-6161.1995.tb02031.x · Cited by 109,482 · cited 1×
“This process was repeated for all domain pairs, and p values were adjusted for multiple hypothesis testing (Benjamini and Hochberg, 1995).”
Emergence of Scaling in Random Networks
Barabási, A.-L., & Albert, R. (1999) · Science · doi:10.1126/science.286.5439.509 · Cited by 36,135 · cited 1×
“…fraction of proteins observed across the range of vertex degrees follows a linear trend for degrees above 4 that is consistent with power law behavior typical of scale-free networks (Barabasi and Albert, 1999) and has been observed in protein interaction and metabolic networks (Vidal et al., 2011).”
Eng, J. K., McCormack, A. L., & Yates, J. R. (1994) · Journal of the American Society for Mass Spectrometry · doi:10.1016/1044-0305(94)80016-2 · Cited by 6,484 · cited 1×
“Using Sequest (Eng et al., 1994), spectra were searched against human protein sequences from Uniprot (Magrane and Consortium, 2011) and common contaminants.”
Pfam: the protein families database
Finn, R. D., Bateman, A., Clements, J., Coggill, P., Eberhardt, R. Y., Eddy, S. R., Heger, A., Hetherington, K., Holm, L., Mistry, J., et al. (2014) · Nucleic Acids Research · doi:10.1093/nar/gkt1223 · Cited by 6,148
Fast algorithm for detecting community structure in networks
Newman, M. E. J. (2004) · Physical Review E · doi:10.1103/physreve.69.066133 · Cited by 5,415 · cited 1×
“We have employed a two-stage strategy to map BioPlex community structure, using clique percolation (Palla et al., 2005) to identify 256 communities that were further subdivided via modularity-based clustering (Newman, 2004) (legend continued on next page) subcommunities (Table S3).”
Uncovering the overlapping community structure of complex networks in nature and society
Palla, G., Derényi, I., Farkas, I., & Vicsek, T. (2005) · Nature · doi:10.1038/nature03607 · Cited by 5,373 · cited 2×
“We have employed a two-stage strategy to map BioPlex community structure, using clique percolation (Palla et al., 2005) to identify 256 communities that were further subdivided via modularity-based clustering (Newman, 2004) (legend continued on next page) subcommunities (Table S3).”
Warde-Farley, D., Donaldson, S. L., Comes, O., Zuberi, K., Badrawi, R., Chao, P., Franz, M., Grouios, C., Kazi, F., Lopes, C. T., et al. (2010) · Nucleic Acids Research · doi:10.1093/nar/gkq537 · Cited by 4,835 · cited 6×
“To enable more extensive comparison, we compiled all human physical interactions reported in CORUM, BioGRID (Stark et al., 2011), GeneMania, STRING, and MINT (Licata et al., 2012).”
InfluentialFunctional organization of the yeast proteome by systematic analysis of protein complexes
Gavin, A., Böesche, M., Krause, R., Grandi, P., Marzioch, M., Bauer, A., Schultz, J., Rick, J. M., Michon, A., Cruciat, C., et al. (2002) · Nature · doi:10.1038/415141a · Cited by 4,729 · cited 2×
“AP-MS has previously mapped a substantial fraction of yeast (Gavin et al., 2002; Ho et al., 2002; Krogan et al., 2006) and Drosophila (Guruharsha et al.”
STRING v9.1: protein-protein interaction networks, with increased coverage and integration
Franceschini, A., Szklarczyk, D., Frankild, S., Kuhn, M., Simonovic, M., Roth, A., Lin, J., Minguez, P., Bork, P., von Mering, C., et al. (2012) · Nucleic Acids Research · doi:10.1093/nar/gks1094 · Cited by 4,398 · cited 7×
“To enable more extensive comparison, we compiled all human physical interactions reported in CORUM, BioGRID (Stark et al., 2011), GeneMania, STRING, and MINT (Licata et al., 2012).”
InfluentialElias, J. E., & Gygi, S. P. (2007) · Nature Methods · doi:10.1038/nmeth1019 · Cited by 3,925 · cited 2×
“The target-decoy method (Elias and Gygi, 2007) was used to filter each LC-MS dataset to a preliminary 1% protein FDR.”
Self-citation
Cited by
Sorted by citations
Items 201–300 of 1,001
Maron, B. A., Wang, R., Shevtsov, S., Drakos, S., Arons, E., Wever-Pinzon, O., Huggins, G. S., Samokhin, A. O., Oldham, W. M., Aguib, Y., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-21146-y · Cited by 90
Richardson, K., Langridge, D., Dixit, S. M., & Ruotolo, B. T. (2021) · Analytical Chemistry · doi:10.1021/acs.analchem.0c04948 · Cited by 100
Calabrese, G., Molzahn, C. M., & Mayor, T. (2022) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2022.102062 · Cited by 92
Discovering cellular protein‐protein interactions: Technological strategies and opportunities
Titeca, K., Lemmens, I. H., Tavernier, J. H., & Eyckerman, S. (2018) · Mass Spectrometry Reviews · doi:10.1002/mas.21574 · Cited by 95
Centriolar satellites are required for efficient ciliogenesis and ciliary content regulation
Odabasi, E., Ohlsen, S. K., Gül, Ş., Kavaklı, İ. H., Andersen, J., & Firat‐Karalar, E. N. (2019) · EMBO Reports · doi:10.15252/embr.201947723 · Cited by 88
“Supporting the relationship between IFT machinery and satellites, proteomics studies identified putative interactions of satellites with various IFT-A and IFT-B components, supporting the functional relationship between the IFT machinery and satellites [27,65,66].”
Structure of the endosomal Commander complex linked to Ritscher-Schinzel syndrome
Healy, M. D., McNally, K. E., Butkovič, R., Chilton, M., Kato, K., Sacharz, J., McConville, C., Moody, E. R. R., Shaw, S., Planelles-Herrero, V. J., et al. (2023) · Cell · doi:10.1016/j.cell.2023.04.003 · Cited by 91
“VPS35L (16-38) Genscript N/A VPS35L (27-38) Genscript N/A”
BackgroundBonacci, T., Suzuki, A., Grant, G. D., Stanley, N., Cook, J. G., Brown, N. G., & Emanuele, M. J. (2018) · The EMBO Journal · doi:10.15252/embj.201798701 · Cited by 91
“However, it is unknown whether Cezanne binds directly to the APC/C. Cezanne has not been identified in large-scale protein interaction mass spectrometry studies, which surveyed a subset of APC/C subunits (Huttlin et al , 2015).”
Impact of Mitochondrial Fatty Acid Synthesis on Mitochondrial Biogenesis
Nowinski, S. M., Vranken, J. G. V., Dove, K. K., & Rutter, J. P. (2018) · Current Biology · doi:10.1016/j.cub.2018.08.022 · Cited by 90
The interferon-inducible isoform of NCOA7 inhibits endosome-mediated viral entry
Doyle, T., Moncorgé, O., Bonaventure, B., Pollpeter, D., Lussignol, M., Tauziet, M., Apolonia, L., Catanese, M. T., Goujon, C., & Malim, M. H. (2018) · Nature Microbiology · doi:10.1038/s41564-018-0273-9 · Cited by 87
“The endocytic pathway is also important for the entry of many bacterial pathogens and toxins and a role for OXR1/NCOA7 homologues has been suggested in protection from Vibrio cholera infection in Drosophila models (27).”
InfluentialPrimPol is required for replication reinitiation after mtDNA damage
Torregrosa‐Muñumer, R., Forslund, J. M. E., Goffart, S., Pfeiffer, A., Stojkovič, G., Carvalho, G., Al-Furoukh, N., Blanco, L., Wanrooij, S., & Pohjoismäki, J. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1705367114 · Cited by 88
“Furthermore, TWNK is also reported as a PrimPol (as CCDC111) partner in the BioPlex database (33).”
BackgroundPaci, P., Fiscon, G., Conte, F., Wang, R., Farina, L., & Loscalzo, J. (2021) · npj Systems Biology and Applications · doi:10.1038/s41540-020-00168-0 · Cited by 87
Down the Iron Path: Mitochondrial Iron Homeostasis and Beyond
Dietz, J. V., Fox, J. L., & Khalimonchuk, O. (2021) · Cells · doi:10.3390/cells10092198 · Cited by 98
“This sulfur, held on a catalytic cysteine as a persulfide, is transferred to the ISC scaffold protein ISCU, which directly interacts with NFS1, ISD11, and the mitochondrial acyl carrier protein (ACP1) to form the ISC biogenesis scaffold [228,229].”
BackgroundNishijima, Y., Hagiya, Y., Kubo, T., Takei, R., Katoh, Y., & Nakayama, K. (2017) · Molecular Biology of the Cell · doi:10.1091/mbc.e17-01-0017 · Cited by 86
“…ciliogenesis (Yan et al., 2006; Lee and Stearns, 2013) and three independent interactome analyses suggested an interaction between CEP19 and FGFR1OP (Rolland et al., 2014; Gupta et al., 2015; Huttlin et al., 2015), we then addressed the possibility that CEP19 and FGFR1OP associate with each other.”
BackgroundPooled CRISPR screens with imaging on microraft arrays reveals stress granule-regulatory factors
Wheeler, E. C., Vu, A. Q., Einstein, J. M., DiSalvo, M., Ahmed, N., Nostrand, E. L. V., Shishkin, A. A., Jin, W., Allbritton, N. L., & Yeo, G. W.-M. (2020) · Nature Methods · doi:10.1038/s41592-020-0826-8 · Cited by 86
“Protein-protein interactions curated from BioPlex data 47 and recent publications 34 .”
Dimerization quality control ensures neuronal development and survival
Mena, E. L., Kjolby, R. A. S., Saxton, R. A., Werner, A. A., Lew, B. G., Boyle, J. M., Harland, R. M., & Rapé, M. (2018) · Science · doi:10.1126/science.aap8236 · Cited by 83
“Moreover, recurrent interaction modules may retain affinity for homologous domains in other proteins (1, 5), which can result in heterooligomers with altered signaling output.”
BackgroundMethodInfluentialCDC20B is required for deuterosome-mediated centriole production in multiciliated cells
Revinski, D. R., Zaragosi, L., Boutin, C., García, S. R., Deprez, M., Thomé, V., Rosnet, O., Gay, A.-S., Mercey, O., Paquet, A. C., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-06768-z · Cited by 91
Cid-Samper, F., Gelabert‐Baldrich, M., Lang, B., Lorenzo-Gotor, N., Ponti, R. D., Severijnen, L.-A. W. F. M., Bolognesi, B., Gelpí, E., Hukema, R. K., Botta‐Orfila, T., et al. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.11.076 · Cited by 86
“Human PPIs were taken from the BioPlex database (Huttlin et al., 2015) that includes highly curated data produced by high-throughput affinity-purification mass spectrometry.”
BackgroundMethodInfluentialA multi-scale map of cell structure fusing protein images and interactions
Qin, Y., Huttlin, E. L., Winsnes, C. F., Gosztyla, M. L., Wacheul, L., Kelly, M. R., Blue, S. M., Zheng, F., Chen, M., Schaffer, L. V., et al. (2021) · Nature · doi:10.1038/s41586-021-04115-9 · Cited by 82
A role for Mitochondrial Rho GTPase 1 (MIRO1) in motility and membrane dynamics of peroxisomes
Castro, I. G., Richards, D. M., Metz, J., Costello, J. L., Passmore, J. B., Schrader, T. A., Gouveia, A., Ribeiro, D., & Schrader, M. (2018) · Traffic · doi:10.1111/tra.12549 · Cited by 91
“Additionally, in a high-throughput interaction study, MIRO1 was identified as a PEX19 interaction partner.(37) These find-”
BackgroundMiyakawa, K., Nishi, M., Ogawa, M., Matsunaga, S., Sugiyama, M., Nishitsuji, H., Kimura, H., Ohnishi, M., Watashi, K., Shimotohno, K., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-28171-5 · Cited by 85
Capturing RNA–protein interaction via CRUIS
Zhang, Z., Sun, W., Shi, T., Lu, P., Zhuang, M., & Liu, J. (2020) · Nucleic Acids Research · doi:10.1093/nar/gkaa143 · Cited by 86
Xu, J., Zhang, P., Huang, Y., Zhou, Y., Hou, Y., Bekris, L. M., Lathia, J. D., Chiang, C., Li, L., Pieper, A. A., et al. (2021) · Genome Research · doi:10.1101/gr.272484.120 · Cited by 83
Recent technical advances in proteomics
Yates, J. R. (2019) · F1000Research · doi:10.12688/f1000research.16987.1 · Cited by 85
Instrumentation at the Leading Edge of Proteomics
Peters-Clarke, T. M., Coon, J. J., & Riley, N. M. (2024) · Analytical Chemistry · doi:10.1021/acs.analchem.3c04497 · Cited by 89
Cross-linking/mass spectrometry to get a closer view on protein interaction networks
Iacobucci, C., Götze, M., & Sinz, A. (2019) · Current Opinion in Biotechnology · doi:10.1016/j.copbio.2019.12.009 · Cited by 82
Kotlyar, M., Pastrello, C., Ahmed, Z., Chee, J., Varyova, Z., & Jurišica, I. (2021) · Nucleic Acids Research · doi:10.1093/nar/gkab1034 · Cited by 83
Mitochondria-Associated Membranes (MAMs): Overview and Its Role in Parkinson’s Disease
Rodríguez‐Arribas, M., Yakhine-Diop, S. M. S., Pedro, J. M. B., Gómez‐Suaga, P., Gómez‐Sánchez, R., Martínez-Chacón, G., Fuentes, J. M., González‐Polo, R. A., & Niso‐Santano, M. (2016) · Molecular Neurobiology · doi:10.1007/s12035-016-0140-8 · Cited by 82
“This interaction forms a molecular scaffold which tethers ER regions to mitochondria, regulating MAM functions, like the Ca exchange between the two organelles [45,44,46].”
Interpretation of cancer mutations using a multiscale map of protein systems
Zheng, F., Kelly, M. R., Ramms, D. J., Heintschel, M. L., Tao, K., Tutuncuoglu, B., Lee, J. J., Ono, K., Foussard, H., Chen, M., et al. (2021) · Science · doi:10.1126/science.abf3067 · Cited by 81
Progranulin promotes peripheral nerve regeneration and reinnervation: role of notch signaling
Altmann, C., Vasić, V., Hardt, S., Heidler, J., Häußler, A., Wittig, I., Schmidt, M. H. H., & Tegeder, I. (2016) · Molecular Neurodegeneration · doi:10.1186/s13024-016-0132-1 · Cited by 81
“Recent high-throughput affinity chromatography analyses of protein interactomes did not retrieve sortilin as a progranulin binding partner but suggest interactions of progranulin with EGFR and with soluble Notch ligands [21, 22] pointing to EGF domain rich proteins, and possibly Notch as putative progranulin targets.”
BackgroundThe Gag protein PEG10 binds to RNA and regulates trophoblast stem cell lineage specification
Abed, M., Verschueren, E., Budayeva, H. G., Liu, P. J., Kirkpatrick, D. S., Reja, R., Kummerfeld, S., Webster, J. D., Gierke, S., Reichelt, M., et al. (2019) · PLoS ONE · doi:10.1371/journal.pone.0214110 · Cited by 81
BioPlex Display: An Interactive Suite for Large-Scale AP–MS Protein–Protein Interaction Data
Schweppe, D. K., Huttlin, E. L., Harper, J. W., & Gygi, S. P. (2017) · Journal of Proteome Research · doi:10.1021/acs.jproteome.7b00572 · Cited by 82
Hanada, K. (2018) · Journal of Lipid Research · doi:10.1194/jlr.r085324 · Cited by 79
VPS13A, a closely associated mitochondrial protein, is required for efficient lysosomal degradation
Muñoz‐Braceras, S., Tornero-Écija, A., Vincent, O., & Escalante, R. (2019) · Disease Models & Mechanisms · doi:10.1242/dmm.036681 · Cited by 87
“The interaction of VPS13C with diverse RAB GTPases, including RAB7A, has been revealed by different proteomic studies (Behrends et al., 2010; Huttlin et al., 2015; McCray et al., 2010), and VPS13B has been described as an effector of RAB6 (also known as RAB6A) (Seifert et al., 2015).”
The DifferentialNet database of differential protein–protein interactions in human tissues
Basha, O., Shpringer, R., Argov, C. M., & Yeger‐Lotem, E. (2017) · Nucleic Acids Research · doi:10.1093/nar/gkx981 · Cited by 79
Targeting receptor complexes: a new dimension in drug discovery
Ishoey, M., Clemmensen, L. S., Bredt, D. S., Bettler, B., & Strømgaard, K. (2020) · Nature Reviews Drug Discovery · doi:10.1038/s41573-020-0086-4 · Cited by 79
High-density chemical cross-linking for modeling protein interactions
Mintseris, J., & Gygi, S. P. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1902931116 · Cited by 80
“interactions in the cell (1) promise to improve our understanding of cellular protein machinery.”
BackgroundBartolec, T. K., Vázquez-Campos, X., Norman, A. R., Luong, C., Johnson, M., Payne, R. J., Wilkins, M. R., Mackay, J. P., & Low, J. K. K. (2023) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2219418120 · Cited by 83
“An example of a corroborated dimer interface without any structural precedent in the PDB is the interaction of STX18 (Uniprot: Q9P2W9) and SCFD1 (Uniprot: Q8WVM8) was previously described by four studies (54–57).”
Systems-wide Studies Uncover Commander, a Multiprotein Complex Essential to Human Development
Mallam, A. L., & Marcotte, E. M. (2017) · Cell Systems · doi:10.1016/j.cels.2017.04.006 · Cited by 94
Maximizing binary interactome mapping with a minimal number of assays
Choi, S. G., Olivet, J., Cassonnet, P., Vidalain, P., Luck, K., Lambourne, L., Spirohn, K., Lemmens, I. H., Santos, M. D., Demeret, C., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-11809-2 · Cited by 76
Centriolar satellite biogenesis and function in vertebrate cells
Prosser, S. L., & Pelletier, L. (2020) · Journal of Cell Science · doi:10.1242/jcs.239566 · Cited by 82
DNAJC12 deficiency: A new strategy in the diagnosis of hyperphenylalaninemias
Blau, N., Martı́nez, A., Hoffmann, G. F., & Thöny, B. (2017) · Molecular Genetics and Metabolism · doi:10.1016/j.ymgme.2017.11.005 · Cited by 75
BLOC-1 is required for selective membrane protein trafficking from endosomes to primary cilia
Monis, W. J., Faúndez, V., & Pazour, G. J. (2017) · The Journal of Cell Biology · doi:10.1083/jcb.201611138 · Cited by 75
“However, it is likely that IFT20 interacts with the entire exocyst complex, as the Sec10 subunit also interacts with IFT20, and a large-scale proteomic study found IFT20 binding to multiple components (Exoc3, Exoc7, Exoc5, and Exoc6B; Fogelgren et al., 2011; Huttlin et al., 2015).”
BackgroundAdvances in protein-protein interaction network analysis for Parkinson's disease
Tomkins, J. E., & Manzoni, C. (2021) · Neurobiology of Disease · doi:10.1016/j.nbd.2021.105395 · Cited by 78
Haase, G., & Rabouille, C. (2015) · Frontiers in Neuroscience · doi:10.3389/fnins.2015.00448 · Cited by 78
“This is likely due to the pleiotropic effects of VAP-B on Golgi-mediated transport pathways (Peretti et al., 2008) where it interacts with numerous Golgi-associated proteins (Huttlin et al., 2015) and microtubules (Skehel et al., 2000).”
BackgroundAli, O., Cerjak, D., Kent, J. W., James, R. G., Blangero, J., Carless, M. A., & Zhang, Y. (2016) · Epigenetics · doi:10.1080/15592294.2016.1216284 · Cited by 75
Hesketh, G. G., Youn, J., Samavarchi‐Tehrani, P., Raught, B., & Gingras, A. (2017) · Methods in molecular biology · doi:10.1007/978-1-4939-6747-6_10 · Cited by 77
Mapping the multiscale structure of biological systems
Schaffer, L. V., & Ideker, T. (2021) · Cell Systems · doi:10.1016/j.cels.2021.05.012 · Cited by 75
“(D) Protein interaction network from BioPlex, AP-MS data of HEK293 cells (Huttlin et al., 2015).”
MethodMolecular Principles of Gene Fusion Mediated Rewiring of Protein Interaction Networks in Cancer
Latysheva, N. S., Oates, M. E., Maddox, L., Flock, T., Gough, J., Buljan, M., Weatheritt, R. J., & Babu, M. M. (2016) · Molecular Cell · doi:10.1016/j.molcel.2016.07.008 · Cited by 74
“Although we find that parent genes from metastatic tumours have borderline significantly higher degree, betweenness and hub scores compared to parent genes from primary tumours, an alternative PPI dataset derived from MS data (Huttlin et al., 2015) does not replicate this trend (data not shown).”
BackgroundMethodInfluentialLau, D. H. W., Hartopp, N., Welsh, N. J., Mueller, S., Glennon, E. B. C., Mórotz, G. M., Annibali, A., Gómez‐Suaga, P., Stoica, R., Paillusson, S., et al. (2018) · Cell Death and Disease · doi:10.1038/s41419-017-0022-7 · Cited by 77
Landscape of the Plasmodium Interactome Reveals Both Conserved and Species-Specific Functionality
Hillier, C., Pardo, M., Yu, L., Bushell, E., Sanderson, T., Metcalf, T., Herd, C., Anar, B., Rayner, J. C., Billker, O., et al. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.07.019 · Cited by 74
A protein network map of head and neck cancer reveals PIK3CA mutant drug sensitivity
Swaney, D. L., Ramms, D. J., Wang, Z., Park, J., Goto, Y., Soucheray, M., Bhola, N. E., Kim, K., Zheng, F., Zeng, Y., et al. (2021) · Science · doi:10.1126/science.abf2911 · Cited by 72
“We elected to report a conservative and high-confidence PPI (HC-PPI) map by requiring PPIs to pass stringent criteria by two complementary PPI scoring algorithms: SAINTexpress and CompPASS (see the materials and methods) (22, 37, 38).”
MethodDickinson, Q., & Meyer, J. G. (2022) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1009736 · Cited by 80
“Decades of effort by thousands of scientists has focused on measuring protein structures [1–3] and determining intermolecular binding [4].”
BackgroundIdentifying communities from multiplex biological networks
Didier, G., Brun, C., & Baudot, A. (2015) · PeerJ · doi:10.7717/peerj.1525 · Cited by 78
“They have been thoroughly assessed on biological networks ( Brohée & Van Helden, 2006 ), and are widely used in biology ( Arroyo et al., 2015 ; Wan et al., 2015 ; Huttlin et al., 2015 ; Chapple et al., 2015 ; Katsogiannou et al., 2014 ).”
BackgroundMeasuring intratumor heterogeneity by network entropy using RNA-seq data
Park, Y., Lim, S., Nam, J., & Kim, S. (2016) · Scientific Reports · doi:10.1038/srep37767 · Cited by 77
“BioPlex and HINT were used in inter-PIN comparison study 57,58 .”
MethodSystematic Discovery of Endogenous Human Ribonucleoprotein Complexes
Mallam, A. L., Sae-Lee, W., Schaub, J. M., Tu, F., Battenhouse, A. M., Jang, Y. J., Kim, J., Wallingford, J. B., Finkelstein, I. J., Marcotte, E. M., et al. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.09.060 · Cited by 68
“A world-wide effort is currently under way to systematically identify multi-protein complexes using high-throughput mass spectrometry techniques (Hein et al., 2015; Huttlin et al., 2015), but none of these techniques identify an RNA component within the complexes.”
A rare human centenarian variant of SIRT6 enhances genome stability and interaction with Lamin A
Simon, M., Yang, J., Gigas, J., Earley, E. J., Hillpot, E., Zhang, L., Zagorulya, M., Tombline, G., Gilbert, M., Yuen, S. L., et al. (2022) · The EMBO Journal · doi:10.15252/embj.2021110393 · Cited by 72
MYTHO is a novel regulator of skeletal muscle autophagy and integrity
Leduc‐Gaudet, J., Franco‐Romero, A., Cefis, M., Moamer, A., Broering, F. E., Milan, G., Sartori, R., Chaffer, T. J., Dulac, M., Marcangeli, V., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-36817-1 · Cited by 75
The 7q11.23 Protein DNAJC30 Interacts with ATP Synthase and Links Mitochondria to Brain Development
Tebbenkamp, A. T. N., Varela, L., Choi, J., Paredes, M. I., Giani, A. M., Song, J. E., Šestan-Peša, M., Franjic, D., Sousa, A. M. M., Liu, Z.-W., et al. (2018) · Cell · doi:10.1016/j.cell.2018.09.014 · Cited by 71
Computational analyses of mechanism of action (MoA): data, methods and integration
Trapotsi, M., Hosseini-Gerami, L., & Bender, A. (2021) · RSC Chemical Biology · doi:10.1039/d1cb00069a · Cited by 77
Peroxisomal ABC Transporters: An Update
Tawbeh, A., Gondcaille, C., Trompier, D., & Savary, S. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22116093 · Cited by 68
Hara, A., Kobayashi, H., Asai, N., Saito, S., Higuchi, T., Kato, K., Okumura, T., Bando, Y., Takefuji, M., Mizutani, Y., et al. (2019) · Circulation Research · doi:10.1161/circresaha.119.314806 · Cited by 69
HyperFoods: Machine intelligent mapping of cancer-beating molecules in foods
Veselkov, K., Gonzalez, G., Aljifri, S., Galea, D., Mirnezami, R., Youssef, J., Bronstein, M. M., & Laponogov, I. (2019) · Scientific Reports · doi:10.1038/s41598-019-45349-y · Cited by 71
A Retrospective on eIF2A—and Not the Alpha Subunit of eIF2
Komar, A. A., & Merrick, W. C. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21062054 · Cited by 77
Mapping, modeling, and characterization of protein–protein interactions on a proteomic scale
Cafarelli, T. M., Desbuleux, A., Wang, Y., Choi, S. G., Ridder, D. D., & Vidal, M. (2017) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2017.05.003 · Cited by 75
Dynamic Bayesian Networks for Integrating Multi-omics Time Series Microbiome Data
Ruiz-Perez, D., Lugo-Martinez, J., Bourguignon, N., Mathee, K., Lerner, B., Bar‐Joseph, Z., & Narasimhan, G. (2021) · mSystems · doi:10.1128/msystems.01105-20 · Cited by 73
An Epstein-Barr virus protein interaction map reveals NLRP3 inflammasome evasion via MAVS UFMylation
Yiu, S. P. T., Zerbe, C. M., Vanderwall, D., Huttlin, E. L., Weekes, M. P., & Gewurz, B. E. (2023) · Molecular Cell · doi:10.1016/j.molcel.2023.05.018 · Cited by 73
A computational interactome and functional annotation for the human proteome
Garzón, J. I., Deng, L., Murray, D., Shapira, S. D., Petrey, D. S., & Honig, B. H. (2016) · eLife · doi:10.7554/elife.18715 · Cited by 70
“Notably, due to their smaller sizes, the Y2H and BioPlex datasets recover ~5% (dark purple line) and ~20% (light purple line) of the CORUM complexes, respectively.”
BackgroundMethodInfluentialCdkal1, a type 2 diabetes susceptibility gene, regulates mitochondrial function in adipose tissue
Palmer, C. J., Bruckner, R. J., Paulo, J. A., Kazak, L., Long, J. Z., Mina, A. I., Deng, Z., LeClair, K. B., Hall, J. A., Hong, S., et al. (2017) · Molecular Metabolism · doi:10.1016/j.molmet.2017.07.013 · Cited by 71
“FLAG-tagged CDKAL1 was immunoprecipitated from transfected HEK293 cells and subjected to mass spectrometry in concert with the high-throughput BioPlex protein interactome project [38].”
BackgroundMethodInfluentialBrunet, M. A., Levesque, S. A., Hunting, D. J., Cohen, A. A., & Roucou, X. (2018) · Genome Research · doi:10.1101/gr.230938.117 · Cited by 75
“Mass spectrometry (MS)-based proteomics has emerged as the gold standard technique to assess the protein landscape of a cell or tissue and thus can offer additional evidence beyond ribosome profiling (Aebersold and Mann 2003, 2016; Vogel and Marcotte 2012; Huttlin et al. 2015).”
MethodMuhammed Jamsheer, K., Shukla, B. N., Jindal, S., Gopan, N., Mannully, C. T., & Laxmi, A. (2018) · Journal of Biological Chemistry · doi:10.1074/jbc.ra118.002073 · Cited by 69
Sun, E. W., Guillén-Samander, A., Bian, X., Wu, Y., Cai, Y., Messa, M., & Camilli, P. V. D. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1820156116 · Cited by 68
“Human TMEM24SMP-C2 (36-414) and C2CD2SMP-C2 (39-405) were cloned using NheI and XhoI sites into pET28a vector (Novagen).”
BackgroundMethodAnnexins—Coordinators of Cholesterol Homeostasis in Endocytic Pathways
Rentero, C., Blanco‐Muñoz, P., Meneses‐Salas, E., Grewal, T., & Enrich, C. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19051444 · Cited by 69
“Along these lines, several Annexins interact with the proton pump H+-ATPase subunit VOa2 [211] and the TPC1/2 Ca2+ channels [66].”
BackgroundLy, T., Whigham, A., Clarke, R. G., Murillo, A. B., Estes, B., Madhessian, D., Lundberg, E. K., Wadsworth, P., & Lamond, A. I. (2017) · eLife · doi:10.7554/elife.27574 · Cited by 66
Sample Preparation for Mass Spectrometry-Based Proteomics; from Proteomes to Peptides
ROGERS, J. C., & Bomgarden, R. D. (2016) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-41448-5_3 · Cited by 74
S‐acylated Golga7b stabilises DHHC5 at the plasma membrane to regulate cell adhesion
Woodley, K. T., & Collins, M. O. (2019) · EMBO Reports · doi:10.15252/embr.201847472 · Cited by 67
“In a large-scale affinity purification–mass spectrometry study, Golga7b was identified as a putative interactor of DHHC5 [8].”
Control of mitochondrial function and cell growth by the atypical cadherin Fat1
Cao, L. L., Riascos‐Bernal, D. F., Chinnasamy, P., Dunaway, C. M., Hou, R., Pujato, M. A., O'Rourke, B. P., Miskolci, V., Guo, L., Hodgson, L., et al. (2016) · Nature · doi:10.1038/nature20170 · Cited by 67
ZO-2 Is a Master Regulator of Gene Expression, Cell Proliferation, Cytoarchitecture, and Cell Size
González‐Mariscal, L., Gallego-Gutiérrez, H., González-González, L., & Hernández-Guzmán, C. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20174128 · Cited by 68
“Likewise, affinity purification of epitope tagged proteins followed by MS (AP-MS) identified ZO-2 as an interacting partner of smug, another transcription factor of the snail family [70].”
BackgroundSalas, D., Stacey, R. G., Akinlaja, M. O., & Foster, L. J. (2019) · Molecular & Cellular Proteomics · doi:10.1074/mcp.r119.001803 · Cited by 66
“an interactome), typically done via a machine learning classifier (21, 23, 26, 34, 42, 65, 66).”
MethodWang, Y., Yang, J., Hong, T.-T., Sun, Y., Huang, H., Chen, F., Chen, X., Chen, H., Dong, S., Cui, L., et al. (2020) · Aging Cell · doi:10.1111/acel.13194 · Cited by 62
“Besides, a previous study that using metabolic labeling quantitative MS also suggested that RTN4 may transiently target SIRT2 (Budayeva & Cristea, 2016), and this possible interaction was also identified in other proteomic studies (Huttlin et al., 2015), supporting our results.”
ResultThe Interactome of the VAP Family of Proteins: An Overview
James, C., & Kehlenbach, R. H. (2021) · Cells · doi:10.3390/cells10071780 · Cited by 66
“In comprehensive studies to analyze the entire interactome of mammalian cells, Huttlin and coworkers [43] used a high-throughput affinity-purification mass spectrometry approach (Figure 3A) to identify interacting partners of 2597 human proteins in HEK293T cells.”
BackgroundMethodInfluentialXu, S., Shrestha, R., Karunadasa, S. S., & Xie, P. (2023) · Annual Review of Plant Biology · doi:10.1146/annurev-arplant-070522-052132 · Cited by 68
“AP-MS has been used to map stable protein complexes successfully and, in some cases, to recover transient interactions using modified protocols (8, 42, 47, 81, 82).”
Proteomics to study DNA-bound and chromatin-associated gene regulatory complexes
Wierer, M., & Mann, M. (2016) · Human Molecular Genetics · doi:10.1093/hmg/ddw208 · Cited by 71
Bludau, I., Heusel, M., Frank, M., Rosenberger, G., Hafen, R., Banaei‐Esfahani, A., van Drogen, A., Collins, B. C., Gstaiger, M., & Aebersold, R. H. (2020) · Nature Protocols · doi:10.1038/s41596-020-0332-6 · Cited by 61
“(1) Extraction of protein complexes from a biological sample and fractionation by size exclusion chromatography To minimize complex disassembly under the diluted conditions present after cell or tissue lysis, all processing steps up to the collection of fractions are carried out rapidly, at minimal dilution and below…”
BackgroundMethodInfluentialE3 Ubiquitin Ligase TRIP12: Regulation, Structure, and Physiopathological Functions
Brunet, M., Vargas, C., Larrieu, D., Torrisani, J., & Dufresne, M. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21228515 · Cited by 72
“1 ALYREF Aly/REF export factor bait aff tech co-localization [66] 2 ASXL1 Additional Sex Combs-Like Protein 1 bait biochemical ph ass [53] 3 ATG16L1 Autophagy-related protein 16 like1 bait aff tech ph ass [67] 4 BCAT1 Branched-chain-amino-acid aminotransferase bait ph ass ph ass [68,69] 5 CAPN1 Calpain-1 catalytic sub…”
Mapping, Structure and Modulation of PPI
Martino, E., Chiarugi, S., Margheriti, F., & Garau, G. (2021) · Frontiers in Chemistry · doi:10.3389/fchem.2021.718405 · Cited by 49
The nuclear interactome of DYRK1A reveals a functional role in DNA damage repair
Guard, S. E., Poss, Z. C., Ebmeier, C. C., Pagratis, M., Simpson, H., Taatjes, D. J., & Old, W. M. (2019) · Scientific Reports · doi:10.1038/s41598-019-42990-5 · Cited by 72
Wang, J., Rousseau, J., Kim, E., Ehresmann, S., Cheng, Y.-T., Duraine, L., Zuo, Z., Park, Y.-J., Li‐Kroeger, D., Bi, W., et al. (2019) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2019.11.002 · Cited by 63
Computational Screening of Phase-Separating Proteins
Shen, B., Chen, Z., Yu, C., Chen, T., Shi, M., & Li, T. (2021) · Genomics Proteomics & Bioinformatics · doi:10.1016/j.gpb.2020.11.003 · Cited by 67
“BioPlex database that provides an unbiased mapping of the human PPIs by affinity-purification mass spectrometry might be more appropriate to be incorporated into phase separation prediction [71,72].”
MethodNeggers, J. E., Paolella, B. R., Asfaw, A., Rothberg, M. V., Skipper, T. A., Yang, A., Kalekar, R. L., Krill-Burger, J. M., Dharia, N. V., Kugener, G., et al. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.108493 · Cited by 62
Proteomics Standards Initiative at Twenty Years: Current Activities and Future Work
Deutsch, E. W., Vizcaíno, J. A., Jones, A. R., Binz, P., Lam, H., Klein, J., Bittremieux, W., Pérez‐Riverol, Y., Tabb, D. L., Walzer, M., et al. (2023) · Journal of Proteome Research · doi:10.1021/acs.jproteome.2c00637 · Cited by 67
Pandya, N. J., Klaassen, R. V., van der Schors, R. C., Slotman, J. A., Houtsmuller, A. B., Smit, A. B., & Li, K. W. (2016) · PROTEOMICS · doi:10.1002/pmic.201500400 · Cited by 66
“In this context, a recent interaction proteomics study highlighted a similar example in which 495 proteins were identified from an IP, which eventually was filtered to 16 interactors [20].”
BackgroundGlobal and tissue-specific aging effects on murine proteomes
Keele, G. R., Zhang, J., Szpyt, J., Korstanje, R., Gygi, S. P., Churchill, G. A., & Schweppe, D. K. (2023) · Cell Reports · doi:10.1016/j.celrep.2023.112715 · Cited by 65
Quantitative mapping of protein-peptide affinity landscapes using spectrally encoded beads
Nguyen, H. Q., Roy, J., Harink, B., Damle, N. P., Latorraca, N. R., Baxter, B. C., Brower, K. K., Longwell, S. A., Kortemme, T., Thorn, K. S., et al. (2019) · eLife · doi:10.7554/elife.40499 · Cited by 61
Wu, Z., Liao, Q., & Liu, B. (2019) · Briefings in Bioinformatics · doi:10.1093/bib/bbz085 · Cited by 59
Chen, Q., Lee, K., Yan, S., Kim, S., Wei, C.-H., & Lu, Z. (2020) · PLOS Computational Biology · doi:10.1371/journal.pcbi.1007617 · Cited by 62
“Analyzing functional interactions between proteins, which facilitates the understanding of the cellular processing and characterization, is a routine task in molecular systems biology [55].”
BackgroundXK is a partner for VPS13A: a molecular link between Chorea-Acanthocytosis and McLeod Syndrome
Park, J.-S., & Neiman, A. M. (2020) · Molecular Biology of the Cell · doi:10.1091/mbc.e19-08-0439-t · Cited by 62
“A high-throughput proteomics study in HEK293T cells identified XKR2, the closest paralog to XK as a VPS13A interacting protein (Huttlin et al. , 2015).”
PCprophet: a framework for protein complex prediction and differential analysis using proteomic data
Fossati, A., Li, C., Uliana, F., Wendt, F., Frommelt, F., Sykacek, P., Heusel, M., Hallal, M., Bludau, I., Capraz, T., et al. (2021) · Nature Methods · doi:10.1038/s41592-021-01107-5 · Cited by 58
“3a) or reported NAE1–UBA3 binders like UBE2M 26 or TP53BP2 (ref.”
BackgroundMethodInfluentialUnveiling the hidden interactome of CRBN molecular glues
Baek, K., Metivier, R. J., Burman, S. S. R., Bushman, J. W., Yoon, H., Lumpkin, R. J., Ryan, J. K., Abeja, D. M., Lakshminarayan, M., Yue, H., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-62099-w · Cited by 77
“To establish a work fl ow for the identi fi cation of chemically induced protein-protein interactions, we set out to simplify traditional IP-MS methods.”
InfluentialTUFT1 interacts with RABGAP1 and regulates mTORC1 signaling
Kawasaki, N., Isogaya, K., Dan, S., Yamori, T., Takano, H., Yao, R., Morishita, Y., Taguchi, L., Morikawa, M., Heldin, C., et al. (2018) · Cell Discovery · doi:10.1038/s41421-017-0001-2 · Cited by 67
Chen, P., Han, X., Shaw, T. I., Fu, Y., Sun, H., Niu, M., Wang, Z., Jiao, Y., Teubner, B. J. W., Eddins, D. M., et al. (2022) · Nature Aging · doi:10.1038/s43587-022-00290-0 · Cited by 60
Metadata
- Authors
- Huttlin, E. L., Ting, L., Bruckner, R. J., Gebreab, F., Gygi, M. P., Szpyt, J., Tam, S., Zarraga, G., Colby, G., Baltier, K., Dong, R., Guarani, V., Vaites, L. P., Ordureau, A., Rad, R., Erickson, B. K., Wühr, M., Chick, J., Zhai, B., Kolippakkam, D., Mintseris, J., Obar, R. A., Harris, T., Artavanis-Tsakonas, S., Sowa, M. E., De Camilli, P., Paulo, J. A., Harper, J. W., & Gygi, S. P.
- Affiliations
- Harvard University (US)
- Howard Hughes Medical Institute (US)
- Biogen (United States) (US)
- Corresponding author
- Harper, J. Wade
- Gygi, Steven P.
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2015-07
- Volume
- 162
- Issue
- 2
- Pages
- 425-440
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC4617211
- OpenAlex
- W1611787727
- Cited by
- 1,425
- References
- 41
- Citations by year
- 2026: 46 · 2025: 82 · 2024: 116 · 2023: 105 · 2022: 98 · 2021: 162 · 2020: 159 · 2019: 197 · 2018: 171 · 2017: 147 · 2016: 122 · 2015: 18
- FWCI
- 66.47
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- Damon Runyon Cancer Research Foundation
- Biogen
- Charles A. King Trust
- National Institutes of Health (HG006673)
- National Human Genome Research Institute (U41HG006673)
- National Institute of Diabetes and Digestive and Kidney Diseases (K01DK098285)
- National Institute of Neurological Disorders and Stroke (R37NS036251)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioinformatics and Genomic Networks
- Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Biotin and Related Studies
- Keywords
- BioPlex, human interactome, protein-protein interaction, protein complexes, protein domain interactions, community structure, HEK293T cells, VAPB, amyotrophic lateral sclerosis
- MeSH terms
- Amyotrophic Lateral Sclerosis, Humans, Proteins, Mass Spectrometry, Protein Interaction Mapping, Proteomics, Protein Interaction Maps
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
