Genomes and Genes
Experts and Doctors on zebrafish proteins in Boston, Massachusetts, United States
Locale: Boston, Massachusetts, United States
Topic: zebrafish proteins
- Mosimann C, PanÃ¡kovÃ¡ D, Werdich A, Musso G, Burger A, Lawson K, et al. Chamber identity programs drive early functional partitioning of the heart. Nat Commun. 2015;6:8146 pubmed publisher..Our data establish that the transcriptional program driving cardiac septation regulates physiologic ventricle partitioning, which successively provides mechanical advantages of sequential contraction. ..
- Niethammer P, Grabher C, Look A, Mitchison T. A tissue-scale gradient of hydrogen peroxide mediates rapid wound detection in zebrafish. Nature. 2009;459:996-9 pubmed publisher..This is the first observation, to our knowledge, of a tissue-scale H(2)O(2) pattern, and the first evidence that H(2)O(2) signals to leukocytes in tissues, in addition to its known antiseptic role. ..
- Collavin L, Kirschner M. The secreted Frizzled-related protein Sizzled functions as a negative feedback regulator of extreme ventral mesoderm. Development. 2003;130:805-16 pubmed..Our data are consistent with the existence of some limited self-organizing properties of the extreme ventral mesoderm. ..
- Tang J, Hu G, Hanai J, Yadlapalli G, Lin Y, Zhang B, et al. A critical role for calponin 2 in vascular development. J Biol Chem. 2006;281:6664-72 pubmed..Collectively, these data suggest that calponin 2 plays an important role in the migration of endothelial cells both in vivo and in vitro and that its expression is critical for proper vascular development. ..
- Paik E, de Jong J, Pugach E, Opara P, Zon L. A chemical genetic screen in zebrafish for pathways interacting with cdx4 in primitive hematopoiesis. Zebrafish. 2010;7:61-8 pubmed publisher..The psoralen compounds also disrupted normal A-P patterning of embryos. These compounds modify the cdx4-mutant phenotype and will help elucidate signaling pathways that act downstream or parallel to the cdx4-hox pathway. ..
- Akle V, Guelin E, Yu L, Brassard Giordano H, Slack B, Zhdanova I. F-spondin/spon1b expression patterns in developing and adult zebrafish. PLoS ONE. 2012;7:e37593 pubmed publisher..Together, these findings suggest major roles for F-spondin in the CNS and periphery of the developing and adult vertebrate. ..
- Albertson R, Payne Ferreira T, Postlethwait J, Yelick P. Zebrafish acvr2a and acvr2b exhibit distinct roles in craniofacial development. Dev Dyn. 2005;233:1405-18 pubmed..These studies revealed previously uncharacterized roles for acvr2a and acvr2b in hindbrain and NCC patterning, in NCC derived pharyngeal arch cartilage and joint formation, and in tooth development. ..
- Itoh K, Antipova A, Ratcliffe M, Sokol S. Interaction of dishevelled and Xenopus axin-related protein is required for wnt signal transduction. Mol Cell Biol. 2000;20:2228-38 pubmed..Finally, our data point to a possible mechanism for signal transduction, in which Xdsh prevents beta-catenin degradation by displacing GSK3 from its complex with XARP. ..
- Salic A, Kroll K, Evans L, Kirschner M. Sizzled: a secreted Xwnt8 antagonist expressed in the ventral marginal zone of Xenopus embryos. Development. 1997;124:4739-48 pubmed..szl thus encodes a secreted antagonist of wnt signaling likely involved in inhibiting Xwnt8 and XmyoD ventrally and whose restricted expression represents a new element in the molecular pattern of the ventral marginal zone. ..
- Wingert R, Davidson A. Zebrafish nephrogenesis involves dynamic spatiotemporal expression changes in renal progenitors and essential signals from retinoic acid and irx3b. Dev Dyn. 2011;240:2011-27 pubmed publisher..Our results suggest a model whereby RA patterns the early field of nephron progenitors, with subsequent factors like irx3b acting to refine later progenitor subdomains and ensure activation of segment-specific gene programs. ..
- Fortier S, Yang X, Wang Y, Bennett R, Strauss P. Base excision repair in early zebrafish development: evidence for DNA polymerase switching and standby AP endonuclease activity. Biochemistry. 2009;48:5396-404 pubmed publisher..The switch to normal, adult BER occurs fully when the embryos hatch from the chorionic membrane and encounter normal oxidative stress. ..
- Burns C, Traver D, Mayhall E, Shepard J, Zon L. Hematopoietic stem cell fate is established by the Notch-Runx pathway. Genes Dev. 2005;19:2331-42 pubmed..These data define the Notch-Runx pathway as critical for the developmental specification of HSC fate and the subsequent homeostasis of HSC number, thus providing a mechanism for amplifying stem cells in vivo...
- Qi H, Sarkissian M, Hu G, Wang Z, Bhattacharjee A, Gordon D, et al. Histone H4K20/H3K9 demethylase PHF8 regulates zebrafish brain and craniofacial development. Nature. 2010;466:503-7 pubmed publisher..Our findings indicate that an imbalance of histone methylation dynamics has a critical role in XLMR. ..
- Maroto M, Reshef R, Münsterberg A, Koester S, Goulding M, Lassar A. Ectopic Pax-3 activates MyoD and Myf-5 expression in embryonic mesoderm and neural tissue. Cell. 1997;89:139-48 pubmed..Together, these findings imply that Pax-3 may mediate activation of MyoD and Myf-5 in response to muscle-inducing signals from either the axial tissues or overlying ectoderm and identify Pax-3 as a key regulator of somitic myogenesis. ..
- Landesman Bollag E, Romieu Mourez R, Song D, Sonenshein G, Cardiff R, Seldin D. Protein kinase CK2 in mammary gland tumorigenesis. Oncogene. 2001;20:3247-57 pubmed..Thus, in mice, rats, and humans, dysregulated expression of CK2 is associated with and is capable of contributing to mammary tumorigenesis. Targeted inhibition of CK2 could be useful in the treatment of breast cancer. ..
- Amir A, Barua M, McKnight N, Cheng S, Yuan X, Balk S. A direct beta-catenin-independent interaction between androgen receptor and T cell factor 4. J Biol Chem. 2003;278:30828-34 pubmed
- Trede N, Ota T, Kawasaki H, Paw B, Katz T, Demarest B, et al. Zebrafish mutants with disrupted early T-cell and thymus development identified in early pressure screen. Dev Dyn. 2008;237:2575-84 pubmed publisher..We discuss the advantage of this strategy and the general usefulness of the zebrafish as a model system for vertebrate lymphopoiesis and thymic organogenesis. ..
- Albacker C, Storer N, Langdon E, DiBiase A, Zhou Y, Langenau D, et al. The histone methyltransferase SUV39H1 suppresses embryonal rhabdomyosarcoma formation in zebrafish. PLoS ONE. 2013;8:e64969 pubmed publisher..Gene expression profiling at these stages revealed that in the context of KRAS(G12D) overexpression, SUV39H1 may suppress cell cycle progression. Our studies provide evidence for the role of SUV39H1 as a tumor suppressor...
- Kamel G, Hoyos T, Rochard L, Dougherty M, Kong Y, Tse W, et al. Requirement for frzb and fzd7a in cranial neural crest convergence and extension mechanisms during zebrafish palate and jaw morphogenesis. Dev Biol. 2013;381:423-33 pubmed publisher..lower jaw structures, and integration of wnt-frizzled with endothelin signaling to coordinate shaping of the facial form. ..
- Friedland A, Tzur Y, Esvelt K, COLAIACOVO M, Church G, Calarco J. Heritable genome editing in C. elegans via a CRISPR-Cas9 system. Nat Methods. 2013;10:741-3 pubmed publisher..Our results demonstrate that targeted, heritable genetic alterations can be achieved in C. elegans, providing a convenient and effective approach for generating loss-of-function mutants. ..
- Panàkovà D, Werdich A, Macrae C. Wnt11 patterns a myocardial electrical gradient through regulation of the L-type Ca(2+) channel. Nature. 2010;466:874-8 pubmed publisher..The regulation of cellular coupling through such mechanisms may be a general property of non-canonical Wnt signals. ..
- Fraenkel P, Traver D, Donovan A, Zahrieh D, Zon L. Ferroportin1 is required for normal iron cycling in zebrafish. J Clin Invest. 2005;115:1532-41 pubmed
- Serluca F, Sidow A, Mably J, Fishman M. Partitioning of tissue expression accompanies multiple duplications of the Na+/K+ ATPase alpha subunit gene. Genome Res. 2001;11:1625-31 pubmed..The duplications are accompanied by acquisition of clear functional specialization, consistent with the DDC model of genome evolution. ..
- Capdevila J, Tabin C, Johnson R. Control of dorsoventral somite patterning by Wnt-1 and beta-catenin. Dev Biol. 1998;193:182-94 pubmed..Taken together, our results support a model for somite patterning where sclerotome formation is controlled by the antagonistic activities of Shh and Wnt signaling pathways. ..
- Musson M, Jepeal L, Mabray P, Zhdanova I, Cardoso W, Wolfe M. Expression of glucose-dependent insulinotropic polypeptide in the zebrafish. Am J Physiol Regul Integr Comp Physiol. 2009;297:R1803-12 pubmed publisher..In conclusion, the results of these studies suggest that although the zebrafish appears to be a model of an early stage of evolutionary development of GIP expression, the peptide may not possess incretin properties in this species. ..
- Song D, Sussman D, Seldin D. Endogenous protein kinase CK2 participates in Wnt signaling in mammary epithelial cells. J Biol Chem. 2000;275:23790-7 pubmed..These results demonstrate that endogenous CK2 is a positive regulator of Wnt signaling and growth of mammary epithelial cells. ..
- Watanabe M, Rebbert M, Andreazzoli M, Takahashi N, Toyama R, Zimmerman S, et al. Regulation of the Lim-1 gene is mediated through conserved FAST-1/FoxH1 sites in the first intron. Dev Dyn. 2002;225:448-56 pubmed..These results illuminate the conserved nature of the transcriptional regulation of the Lim-1 gene in different vertebrate animals. ..
- Lee Y, Cope J, Ackermann G, Goishi K, Armstrong E, Paw B, et al. Vascular endothelial growth factor receptor signaling is required for cardiac valve formation in zebrafish. Dev Dyn. 2006;235:29-37 pubmed..Taken together, these data demonstrate a novel function for VEGF-Rs in the endocardial endothelium of the developing cardiac valve. ..
- Ransom D, Bahary N, Niss K, Traver D, Burns C, Trede N, et al. The zebrafish moonshine gene encodes transcriptional intermediary factor 1gamma, an essential regulator of hematopoiesis. PLoS Biol. 2004;2:E237 pubmed..Our results establish a major role for this transcriptional intermediary factor in the differentiation of hematopoietic cells in vertebrates. ..
- D Agati G, Beltre R, Sessa A, Burger A, Zhou Y, Mosimann C, et al. A defect in the mitochondrial protein Mpv17 underlies the transparent casper zebrafish. Dev Biol. 2017;430:11-17 pubmed publisher..Identification of mpv17 mutants will allow for further work probing the relationship between mitochondrial function and pigmentation, which has to date received little attention. ..
- North T, Goessling W, Walkley C, Lengerke C, Kopani K, Lord A, et al. Prostaglandin E2 regulates vertebrate haematopoietic stem cell homeostasis. Nature. 2007;447:1007-11 pubmed..The conserved role for PGE2 in the regulation of vertebrate HSC homeostasis indicates that modulation of the prostaglandin pathway may facilitate expansion of HSC number for therapeutic purposes. ..
- Brott B, Sokol S. Regulation of Wnt/LRP signaling by distinct domains of Dickkopf proteins. Mol Cell Biol. 2002;22:6100-10 pubmed..Our study illustrates how an inhibitor of a pathway may be converted into an activator and is the first study to suggest a molecular mechanism for how a ligand other than Wnt can positively regulate beta-catenin signaling. ..
- Crispino J, Lodish M, Thurberg B, Litovsky S, Collins T, Molkentin J, et al. Proper coronary vascular development and heart morphogenesis depend on interaction of GATA-4 with FOG cofactors. Genes Dev. 2001;15:839-44 pubmed..We also infer that GATA-4 function is dependent on interaction with FOG-2 and, very likely, an additional FOG protein for distinct aspects of heart formation. ..
- Omori Y, Malicki J. oko meduzy and related crumbs genes are determinants of apical cell features in the vertebrate embryo. Curr Biol. 2006;16:945-57 pubmed..On the cellular level, crumbs genes regulate the formation of both ciliary and nonciliary apical membrane compartment. ..
- Storer N, Zon L. Zebrafish models of p53 functions. Cold Spring Harb Perspect Biol. 2010;2:a001123 pubmed publisher..This article will summarize how zebrafish models have been used to reveal numerous, important aspects of p53 function. ..
- Chen M, Zhou Y, Detrich H. Zebrafish mitotic kinesin-like protein 1 (Mklp1) functions in embryonic cytokinesis. Physiol Genomics. 2002;8:51-66 pubmed..Our results indicate that the zebrafish Mklp1 motor performs a critical function that is required for completion of embryonic cytokinesis. ..
- Dougherty M, Kamel G, Shubinets V, Hickey G, Grimaldi M, Liao E. Embryonic fate map of first pharyngeal arch structures in the sox10: kaede zebrafish transgenic model. J Craniofac Surg. 2012;23:1333-7 pubmed..The sox10:kaede transgenic line provides a useful tool for neural crest lineage analysis. These studies illustrate the advantages of the zebrafish model for application in morphogenetic studies of vertebrate craniofacial development. ..
- Corey D, Garcia Anoveros J, Holt J, Kwan K, Lin S, Vollrath M, et al. TRPA1 is a candidate for the mechanosensitive transduction channel of vertebrate hair cells. Nature. 2004;432:723-30 pubmed..TRPA1 is probably a component of the transduction channel itself. ..
- Campbell W, Yang H, Zetterberg H, Baulac S, Sears J, Liu T, et al. Zebrafish lacking Alzheimer presenilin enhancer 2 (Pen-2) demonstrate excessive p53-dependent apoptosis and neuronal loss. J Neurochem. 2006;96:1423-40 pubmed
- Huang H, Kathrein K, Barton A, Gitlin Z, Huang Y, Ward T, et al. A network of epigenetic regulators guides developmental haematopoiesis in vivo. Nat Cell Biol. 2013;15:1516-25 pubmed publisher..Our work provides a comprehensive view of how specific chromatin factors and their associated complexes play a major role in the establishment of haematopoietic cells in vivo. ..
- Bolcome R, Chan J. Constitutive MEK1 activation rescues anthrax lethal toxin-induced vascular effects in vivo. Infect Immun. 2010;78:5043-53 pubmed publisher..This approach may be generally applied to investigate additional pathogen-host interactions and to provide mechanistic insights into host signaling pathways affected by pathogen entry...
- Kishi S, Bayliss P, Uchiyama J, Koshimizu E, Qi J, Nanjappa P, et al. The identification of zebrafish mutants showing alterations in senescence-associated biomarkers. PLoS Genet. 2008;4:e1000152 pubmed publisher..Our current strategy of mutant screening for a senescence-associated biomarker in zebrafish embryos may thus prove to be a useful new tool for the genetic dissection of vertebrate stress response and senescence mechanisms. ..
- Lan F, Bayliss P, Rinn J, Whetstine J, Wang J, Chen S, et al. A histone H3 lysine 27 demethylase regulates animal posterior development. Nature. 2007;449:689-94 pubmed..Taken together, these findings identify a small family of H3K27 demethylases with important, evolutionarily conserved roles in H3K27 methylation regulation and in animal anterior-posterior development. ..
- Lien C, Schebesta M, Makino S, Weber G, Keating M. Gene expression analysis of zebrafish heart regeneration. PLoS Biol. 2006;4:e260 pubmed..Our data indicate that zebrafish heart regeneration is associated with sequentially upregulated wound healing genes and growth factors and suggest that PDGF signaling is required. ..
- Tamai K, Semenov M, Kato Y, Spokony R, Liu C, Katsuyama Y, et al. LDL-receptor-related proteins in Wnt signal transduction. Nature. 2000;407:530-5 pubmed..The extracellular domain of LRP6 bound Wnt-1 and associated with Fz in a Wnt-dependent manner. Our results indicate that LRP6 may be a component of the Wnt receptor complex. ..
- Hanai J, Cao P, Tanksale P, Imamura S, Koshimizu E, Zhao J, et al. The muscle-specific ubiquitin ligase atrogin-1/MAFbx mediates statin-induced muscle toxicity. J Clin Invest. 2007;117:3940-51 pubmed..Collectively, our human, animal, and in vitro findings shed light on the molecular mechanism of statin-induced myopathy and suggest that atrogin-1 may be a critical mediator of the muscle damage induced by statins. ..
- Sang X, Curran M, Wood A. Paracrine insulin-like growth factor signaling influences primordial germ cell migration: in vivo evidence from the zebrafish model. Endocrinology. 2008;149:5035-42 pubmed publisher..Collectively, these studies confirm an in vivo role for IGF signaling in cell migration and identify a candidate ligand gene (igf2b) regulating PGC migration in the zebrafish. ..
- Awatramani R, Soriano P, Rodriguez C, Mai J, Dymecki S. Cryptic boundaries in roof plate and choroid plexus identified by intersectional gene activation. Nat Genet. 2003;35:70-5 pubmed..Our data suggest that the roof plate and choroid plexus may be formed of functional units that are capable of differentially organizing the generation of distinct neuronal cell types at different axial levels. ..
- Payne Ferreira T, Yelick P. Alk8 is required for neural crest cell formation and development of pharyngeal arch cartilages. Dev Dyn. 2003;228:683-96 pubmed
- Gibert Y, Lattanzi V, Zhen A, Vedder L, Brunet F, Faasse S, et al. BMP signaling modulates hepcidin expression in zebrafish embryos independent of hemojuvelin. PLoS ONE. 2011;6:e14553 pubmed publisher..Taken together, these data support an alternative mechanism for hepcidin regulation during zebrafish embryonic development, which is independent of hjv. ..
- Alexander C, Reichsman F, Hinkes M, Lincecum J, Becker K, Cumberledge S, et al. Syndecan-1 is required for Wnt-1-induced mammary tumorigenesis in mice. Nat Genet. 2000;25:329-32 pubmed..Our results provide both genetic and biochemical evidence that syndecan-1 can modulate Wnt signalling, and is critical for Wnt-1-induced tumorigenesis of the mouse mammary gland. ..
- Beyer J, Zhao X, Yee R, Khaliq S, McMahon T, Ying H, et al. The role of crumbs genes in the vertebrate cornea. Invest Ophthalmol Vis Sci. 2010;51:4549-56 pubmed publisher..Corneal defects associated with crumbs gene mutations are very severe in the zebrafish model and, in comparison, appear clinically less pronounced in the human eye. ..
- Zetterberg H, Campbell W, Yang H, Xia W. The cytosolic loop of the gamma-secretase component presenilin enhancer 2 protects zebrafish embryos from apoptosis. J Biol Chem. 2006;281:11933-9 pubmed
- Zhao C, Andreeva V, Gibert Y, Labonty M, Lattanzi V, Prabhudesai S, et al. Tissue specific roles for the ribosome biogenesis factor Wdr43 in zebrafish development. PLoS Genet. 2014;10:e1004074 pubmed publisher..Together, our findings provide new insight into roles for Wdr43 in development, ribosome biogenesis, and also ribosomopathy-induced craniofacial phenotypes including Treacher-Collins Syndrome. ..
- Hong C, Peterson Q, Hong J, Peterson R. Artery/vein specification is governed by opposing phosphatidylinositol-3 kinase and MAP kinase/ERK signaling. Curr Biol. 2006;16:1366-72 pubmed..In summary, chemical genetic analysis has uncovered unanticipated opposing roles of PI3K and ERK in artery/vein specification. ..
- Liao E, Paw B, Oates A, Pratt S, Postlethwait J, Zon L. SCL/Tal-1 transcription factor acts downstream of cloche to specify hematopoietic and vascular progenitors in zebrafish. Genes Dev. 1998;12:621-6 pubmed..Forced expression of SCL in clo embryos rescues the blood and vascular defects, suggesting that SCL acts downstream of clo to specify hematopoietic and vascular differentiation. ..
- Groeneweg J, White Y, Kokel D, Peterson R, Zukerberg L, Berin I, et al. cables1 is required for embryonic neural development: molecular, cellular, and behavioral evidence from the zebrafish. Mol Reprod Dev. 2011;78:22-32 pubmed publisher..Collectively, these data suggest that cables1 is important for neural differentiation during embryogenesis, in a mechanism that likely involves interactions with the Cdk5/p35 kinase pathway. ..
- Yu Q, Geng Y, Sicinski P. Specific protection against breast cancers by cyclin D1 ablation. Nature. 2001;411:1017-21 pubmed..Our results suggest that an anti-cyclin D1 therapy might be highly specific in treating human breast cancers with activated Neu-Ras pathways. ..
- Song D, Dominguez I, Mizuno J, Kaut M, Mohr S, Seldin D. CK2 phosphorylation of the armadillo repeat region of beta-catenin potentiates Wnt signaling. J Biol Chem. 2003;278:24018-25 pubmed..Thus, CK2 is a positive regulator of Wnt signaling through phosphorylation of beta-catenin at Thr393, leading to proteasome resistance and increased protein and co-transcriptional activity. ..
- Davidson A, Ernst P, Wang Y, Dekens M, Kingsley P, Palis J, et al. cdx4 mutants fail to specify blood progenitors and can be rescued by multiple hox genes. Nature. 2003;425:300-6 pubmed..Taken together, these findings demonstrate that cdx4 regulates hox genes and is necessary for the specification of haematopoietic cell fate during vertebrate embryogenesis. ..
- Shaw G, Cope J, Li L, Corson K, Hersey C, Ackermann G, et al. Mitoferrin is essential for erythroid iron assimilation. Nature. 2006;440:96-100 pubmed..Our data show that mfrn functions as the principal mitochondrial iron importer essential for haem biosynthesis in vertebrate erythroblasts...
- Jezewski P, Fang P, Payne Ferreira T, Yelick P. Alternative splicing, phylogenetic analysis, and craniofacial expression of zebrafish tbx22. Dev Dyn. 2009;238:1605-12 pubmed publisher..These studies identify an early transcription factor governing vertebrate facial development, which may underlie common craniofacial birth disorders. Developmental Dynamics 238:1605-1612, 2009. (c) 2009 Wiley-Liss, Inc. ..
- Pfaff K, Straub C, Chiang K, Bear D, Zhou Y, Zon L. The zebra fish cassiopeia mutant reveals that SIL is required for mitotic spindle organization. Mol Cell Biol. 2007;27:5887-97 pubmed..Furthermore, short hairpin RNA knockdown of SIL in human cells recapitulates the zebrafish csp mitotic spindle defects. These data, taken together, identify SIL as a novel, vertebrate-specific regulator of mitotic spindle assembly. ..
- Saslowsky D, Cho J, Chinnapen H, Massol R, Chinnapen D, Wagner J, et al. Intoxication of zebrafish and mammalian cells by cholera toxin depends on the flotillin/reggie proteins but not Derlin-1 or -2. J Clin Invest. 2010;120:4399-4409 pubmed publisher..These results revise current models for CT intoxication and implicate protein scaffolding of lipid rafts in the endo-somal sorting of the toxin-GM1 complex. ..
- Quintana F, Iglesias A, Farez M, Caccamo M, Burns E, Kassam N, et al. Adaptive autoimmunity and Foxp3-based immunoregulation in zebrafish. PLoS ONE. 2010;5:e9478 pubmed publisher..Moreover, they identify the zebrafish as a tool to study the molecular pathways controlling adaptive immunity. ..
- Thompson M, Ransom D, Pratt S, MacLennan H, Kieran M, Detrich H, et al. The cloche and spadetail genes differentially affect hematopoiesis and vasculogenesis. Dev Biol. 1998;197:248-69 pubmed..These studies demonstrate that the molecular mechanisms that regulate hematopoiesis and vasculogenesis have been conserved throughout vertebrate evolution and the clo and spt genes are key regulators of these programs. ..
- Braun D, Rao J, Mollet G, Schapiro D, Daugeron M, Tan W, et al. Mutations in KEOPS-complex genes cause nephrotic syndrome with primary microcephaly. Nat Genet. 2017;49:1529-1538 pubmed publisher..We thus identified four new monogenic causes of GAMOS, describe a link between KEOPS function and human disease, and delineate potential pathogenic mechanisms. ..
- Li E, Truong D, Hallett S, Mukherjee K, Schutte B, Liao E. Rapid functional analysis of computationally complex rare human IRF6 gene variants using a novel zebrafish model. PLoS Genet. 2017;13:e1007009 pubmed publisher..Furthermore, it unlocked the possibility for characterizing yet undiscovered human IRF6 missense gene variants from orofacial cleft patients, and illustrated a generalizable functional genomics paradigm in personalized medicine. ..