Gabriela Fragiadakis, PhD

Education
08/2019 - Postdoctoral training, Stanford School of Medicine
PhD, 08/2016 - Microbiology & Immunology, Stanford School of Medicine
BA, 05/2011 - Molecular and Cellular Biology, University of California, Berkeley
Websites
Publications

  1. Mennillo E, Kim YJ, Lee G, Rusu I, Patel RK, Dorman LC, Flynn E, Li S, Bain JL, Andersen C, Rao A, Tamaki S, Tsui J, Shen A, Lotstein ML, Rahim M, Naser M, Bernard-Vazquez F, Eckalbar W, Cho SJ, Beck K, El-Nachef N, Lewin S, Selvig DR, Terdiman JP, Mahadevan U, Oh DY, Fragiadakis GK, Pisco A, Combes AJ, Kattah MG. Single-cell and spatial multi-omics highlight effects of anti-integrin therapy across cellular compartments in ulcerative colitis. Nature communications 2024. PMID: 38374043


  2. Mennillo E, Kim YJ, Rusu I, Lee G, Dorman LC, Bernard-Vazquez F, Bain JL, Patel R, Andersen C, Rao A, Tamaki S, Tsui J, Shen A, Naser M, Eckalbar W, Cho SJ, Beck K, El-Nachef N, Lewin S, Selvig DR, Terdiman JP, Mahadevan U, Oh DY, Fragiadakis GK, Pisco A, Combes AJ, Kattah MG. Single-cell and spatial multi-omics identify innate and stromal modules targeted by anti-integrin therapy in ulcerative colitis. bioRxiv : the preprint server for biology 2023. PMID: 36711576


  3. Cutts Z, Patterson S, Maliskova L, Taylor KE, Ye C, Dall'Era M, Yazdany J, Criswell L, Fragiadakis GK, Langelier C, Capra JA, Sirota M, Lanata CM. Cell-Specific Transposable Element Gene Expression Analysis Identifies Associations with Systemic Lupus Erythematosus Phenotypes. bioRxiv : the preprint server for biology 2023. PMID: 38076936


  4. Locher V, Park S, Bunis DG, Makredes S, Mayer M, Burt TD, Fragiadakis GK, Halkias J. Homeostatic cytokines reciprocally modulate the emergence of prenatal effector PLZF+CD4+ T cells in humans. JCI insight 2023. PMID: 37856221


  5. Gygi JP, Maguire C, Patel RK, Shinde P, Konstorum A, Shannon CP, Xu L, Hoch A, Jayavelu ND, Network I, Haddad EK, Reed EF, Kraft M, McComsey GA, Metcalf J, Ozonoff A, Esserman D, Cairns CB, Rouphael N, Bosinger SE, Kim-Schulze S, Krammer F, Rosen LB, van Bakel H, Wilson M, Eckalbar W, Maecker H, Langelier CR, Steen H, Altman MC, Montgomery RR, Levy O, Melamed E, Pulendran B, Diray-Arce J, Smolen KK, Fragiadakis GK, Becker PM, Augustine AD, Sekaly RP, Ehrlich LIR, Fourati S, Peters B, Kleinstein SH, Guan L. Integrated longitudinal multi-omics study identifies immune programs associated with COVID-19 severity and mortality in 1152 hospitalized participants. bioRxiv : the preprint server for biology 2023. PMID: 37986828


  6. Patel RK, Jaszczak RG, Im K, Carey ND, Courau T, Bunis DG, Samad B, Avanesyan L, Chew NW, Stenske S, Jespersen JM, Publicover J, Edwards AW, Naser M, Rao AA, Lupin-Jimenez L, Krummel MF, Cooper S, Baron JL, Combes AJ, Fragiadakis GK. Cyclone: an accessible pipeline to analyze, evaluate, and optimize multiparametric cytometry data. Frontiers in immunology 2023. PMID: 37731497


  7. Hackney JA, Shivram H, Vander Heiden J, Overall C, Orozco L, Gao X, Kim E, West N, Qamra A, Chang D, Chakrabarti A, Choy DF, Combes AJ, Courau T, Fragiadakis GK, Rao AA, Ray A, Tsui J, Hu K, Kuhn NF, Krummel MF, Erle DJ, Kangelaris K, Sarma A, Lyon Z, Calfee CS, Woodruff PG, Ghale R, Mick E, Byrne A, Zha BS, Langelier C, Hendrickson CM, van der Wijst MGP, Hartoularos GC, Grant T, Bueno R, Lee DS, Greenland JR, Sun Y, Perez R, Ogorodnikov A, Ward A, Ye CJ, UCSF COMET Consortium, Ramalingam T, McBride JM, Cai F, Teterina A, Bao M, Tsai L, Rosas IO, Regev A, Kapadia SB, Bauer RN, Rosenberger CM. A myeloid program associated with COVID-19 severity is decreased by therapeutic blockade of IL-6 signaling. iScience 2023. PMID: 37810211


  8. Fragiadakis G, Neyton L, Patel R, Sarma A, Consortium UC, Willmore A, Haller SC, Kangelaris K, Eckalbar W, Erle D, Krummel M, Hendrickson C, Woodruff P, Langelier C, Calfee C. Distinct pulmonary and systemic effects of dexamethasone in severe COVID-19. Research square 2023. PMID: 37577607


  9. Flynn E, Almonte-Loya A, Fragiadakis GK. Single-Cell Multiomics. Annual review of biomedical data science 2023. PMID: 37159875


  10. Patel RK, Jaszczak RG, Kwok I, Carey ND, Courau T, Bunis D, Samad B, Avanesyan L, Chew NW, Stenske S, Jespersen JM, Publicover J, Edwards A, Naser M, Rao AA, Lupin-Jimenez L, Krummel MF, Cooper S, Baron J, Combes AJ, Fragiadakis GK. Cyclone: an accessible pipeline to analyze, evaluate and optimize multiparametric cytometry data. bioRxiv : the preprint server for biology 2023. PMID: 36945648


  11. Hysenaj L, Little S, Kulhanek K, Magnen M, Bahl K, Gbenedio OM, Prinz M, Rodriguez L, Andersen C, Rao AA, Shen A, Lone JC, Lupin-Jimenez LC, Bonser LR, Serwas NK, Mick E, Khalid MM, Taha TY, Kumar R, Li JZ, Ding VW, Matsumoto S, Maishan M, Sreekumar B, Simoneau C, Nazarenko I, Tomlinson MG, Khan K, von Gottberg A, Sigal A, Looney MR, Fragiadakis GK, Jablons DM, Langelier CR, Matthay M, Krummel M, Erle DJ, Combes AJ, Sil A, Ott M, Kratz JR, Roose JP. SARS-CoV-2 infection of airway organoids reveals conserved use of Tetraspanin-8 by Ancestral, Delta, and Omicron variants. Stem cell reports 2023. PMID: 36827975


  12. Wastyk HC, Perelman D, Topf M, Fragiadakis GK, Robinson JL, Sonnenburg JL, Gardner CD, Sonnenburg ED. Randomized controlled trial demonstrates response to a probiotic intervention for metabolic syndrome that may correspond to diet. Gut microbes 2023. PMID: 36803658


  13. Li X, Perelman D, Leong AK, Fragiadakis G, Gardner CD, Snyder MP. Distinct factors associated with short-term and long-term weight loss induced by low-fat or low-carbohydrate diet intervention. Cell reports. Medicine 2022. PMID: 36516846


  14. Belonwu SA, Li Y, Bunis DG, Rao AA, Solsberg CW, Oskotsky T, Taubes AL, Grone B, Zalocusky KA, Fragiadakis GK, Huang Y, Sirota M. Bioinformatics Analysis of Publicly Available Single-Nuclei Transcriptomics Alzheimer's Disease Datasets Reveals APOE Genotype-Specific Changes Across Cell Types in Two Brain Regions. A pilot telephone-based intervention for patients with poorly-controlled diabetes mellitus. 2022. PMID: 35572130


  15. Fragiadakis GK, Bjornson-Hooper ZB, Madhireddy D, Sachs K, Chen H, McIlwain DR, Spitzer MH, Bendall SC, Nolan GP. Variation of Immune Cell Responses in Humans Reveals Sex-Specific Coordinated Signaling Across Cell Types. A pilot telephone-based intervention for patients with poorly-controlled diabetes mellitus. 2022. PMID: 35419006


  16. Bjornson-Hooper ZB, Fragiadakis GK, Spitzer MH, Chen H, Madhireddy D, Hu K, Lundsten K, McIlwain DR, Nolan GP. A Comprehensive Atlas of Immunological Differences Between Humans, Mice, and Non-Human Primates. A pilot telephone-based intervention for patients with poorly-controlled diabetes mellitus. 2022. PMID: 35359965


  17. Combes AJ, Samad B, Tsui J, Chew NW, Yan P, Reeder GC, Kushnoor D, Shen A, Davidson B, Barczak AJ, Adkisson M, Edwards A, Naser M, Barry KC, Courau T, Hammoudi T, Argüello RJ, Rao AA, Olshen AB, Immunoprofiler Consortium, Cai C, Zhan J, Davis KC, Kelley RK, Chapman JS, Atreya CE, Patel A, Daud AI, Ha P, Diaz AA, Kratz JR, Collisson EA, Fragiadakis GK, Erle DJ, Boissonnas A, Asthana S, Chan V, Krummel MF. Discovering dominant tumor immune archetypes in a pan-cancer census. A pilot telephone-based intervention for patients with poorly-controlled diabetes mellitus. 2021. PMID: 34963056


  18. Belonwu SA, Li Y, Bunis D, Rao AA, Solsberg CW, Tang A, Fragiadakis GK, Dubal DB, Oskotsky T, Sirota M. Sex-Stratified Single-Cell RNA-Seq Analysis Identifies Sex-Specific and Cell Type-Specific Transcriptional Responses in Alzheimer's Disease Across Two Brain Regions. A pilot telephone-based intervention for patients with poorly-controlled diabetes mellitus. 2021. PMID: 34669146


  19. Weiner J, Suwalski P, Holtgrewe M, Rakitko A, Thibeault C, Müller M, Patriki D, Quedenau C, Krüger U, Ilinsky V, Popov I, Balnis J, Jaitovich A, Helbig ET, Lippert LJ, Stubbemann P, Real LM, Macías J, Pineda JA, Fernandez-Fuertes M, Wang X, Karadeniz Z, Saccomanno J, Doehn JM, Hübner RH, Hinzmann B, Salvo M, Blueher A, Siemann S, Jurisic S, Beer JH, Rutishauser J, Wiggli B, Schmid H, Danninger K, Binder R, Corman VM, Mühlemann B, Arjun Arkal R, Fragiadakis GK, Mick E, Comet C, Calfee CS, Erle DJ, Hendrickson CM, Kangelaris KN, Krummel MF, Woodruff PG, Langelier CR, Venkataramani U, García F, Zyla J, Drosten C, Alice B, Jones TC, Suttorp N, Witzenrath M, Hippenstiel S, Zemojtel T, Skurk C, Wolfgang P, Borodina T, Pa-Covid SG, Ripke S, Sander LE, Beule D, Landmesser U, Guettouche T, Kurth F, Heidecker B. Increased risk of severe clinical course of COVID-19 in carriers of HLA-C*04:01. EClinicalMedicine 2021. PMID: 34490415


  20. van der Wijst MGP, Vazquez SE, Hartoularos GC, Bastard P, Grant T, Bueno R, Lee DS, Greenland JR, Sun Y, Perez R, Ogorodnikov A, Ward A, Mann SA, Lynch KL, Yun C, Havlir DV, Chamie G, Marquez C, Greenhouse B, Lionakis MS, Norris PJ, Dumont LJ, Kelly K, Zhang P, Zhang Q, Gervais A, Le Voyer T, Whatley A, Si Y, Byrne A, Combes AJ, Rao AA, Song YS, Fragiadakis GK, Kangelaris K, Calfee CS, Erle DJ, Hendrickson C, Krummel MF, Woodruff PG, Langelier CR, Casanova JL, Derisi JL, Anderson MS, Ye CJ, UCSF COMET consortium. Type I interferon autoantibodies are associated with systemic immune alterations in patients with COVID-19. Science translational medicine 2021. PMID: 34429372


  21. Wang VE, Blaser BW, Patel RK, Behbehani GK, Rao AA, Durbin-Johnson B, Jiang T, Logan AC, Settles M, Mannis GN, Olin R, Damon LE, Martin TG, Sayre PH, Gaensler KM, McMahon E, Flanders M, Weinberg V, Ye CJ, Carbone DP, Munster PN, Fragiadakis GK, McCormick F, Andreadis C. Inhibition of MET Signaling with Ficlatuzumab in Combination with Chemotherapy in Refractory AML: Clinical Outcomes and High-Dimensional Analysis. Blood cancer discovery 2021. PMID: 34514432


  22. Wastyk HC, Fragiadakis GK, Perelman D, Dahan D, Merrill BD, Yu FB, Topf M, Gonzalez CG, Van Treuren W, Han S, Robinson JL, Elias JE, Sonnenburg ED, Gardner CD, Sonnenburg JL. Gut-microbiota-targeted diets modulate human immune status. Cell 2021. PMID: 34256014


  23. Hysenaj L, Little S, Kulhanek K, Gbenedio OM, Rodriguez L, Shen A, Lone JC, Lupin-Jimenez LC, Bonser LR, Serwas NK, Bahl K, Mick E, Li JZ, Ding VW, Matsumoto S, Maishan M, Simoneau C, Fragiadakis G, Jablons DM, Langelier CR, Matthay M, Ott M, Krummel M, Combes AJ, Sil A, Erle DJ, Kratz JR, Roose JP. SARS-CoV-2 infection studies in lung organoids identify TSPAN8 as novel mediator. bioRxiv : the preprint server for biology 2021. PMID: 34100012


  24. Hendley AM, Rao AA, Leonhardt L, Ashe S, Smith JA, Giacometti S, Peng XL, Jiang H, Berrios D, Pawlak M, Li LY, Lee J, Collisson EA, Anderson MS, Fragiadakis GK, Yeh JJ, Chun JY, Kim GE, Weaver VM, Hebrok M. Single cell transcriptome analysis defines heterogeneity of the murine pancreatic ductal tree. eLife 2021. PMID: 34009124


  25. Bunis DG, Andrews J, Fragiadakis GK, Burt TD, Sirota M. dittoSeq: Universal User-Friendly Single-Cell and Bulk RNA Sequencing Visualization Toolkit. Bioinformatics (Oxford, England) 2020. PMID: 33313640


  26. van der Wijst MGP, Vazquez SE, Hartoularos GC, Bastard P, Grant T, Bueno R, Lee DS, Greenland JR, Sun Y, Perez R, Ogorodnikov A, Ward A, Mann SA, Lynch KL, Yun C, Havlir DV, Chamie G, Marquez C, Greenhouse B, Lionakis MS, Norris PJ, Dumont LJ, Kelly K, Zhang P, Zhang Q, Gervais A, Voyer TL, Whatley A, Si Y, Byrne A, Combes AJ, Rao AA, Song YS, UCSF COMET consortium , Fragiadakis GK, Kangelaris K, Calfee CS, Erle DJ, Hendrickson C, Krummel MF, Woodruff PG, Langelier CR, Casanova JL, Derisi JL, Anderson MS, Ye CJ. Longitudinal single-cell epitope and RNA-sequencing reveals the immunological impact of type 1 interferon autoantibodies in critical COVID-19. bioRxiv : the preprint server for biology 2021. PMID: 33758859


  27. Chan V, Gherardini PF, Krummel MF, Fragiadakis GK. A "data sharing trust" model for rapid, collaborative science. Cell 2021. PMID: 33545032


  28. Combes AJ, Courau T, Kuhn NF, Hu KH, Ray A, Chen WS, Chew NW, Cleary SJ, Kushnoor D, Reeder GC, Shen A, Tsui J, Hiam-Galvez KJ, Muñoz-Sandoval P, Zhu WS, Lee DS, Sun Y, You R, Magnen M, Rodriguez L, Im KW, Serwas NK, Leligdowicz A, Zamecnik CR, Loudermilk RP, Wilson MR, Ye CJ, Fragiadakis GK, Looney MR, Chan V, Ward A, Carrillo S. Global absence and targeting of protective immune states in severe COVID-19. Nature 2021. PMID: 33494096


  29. Rahil Z, Leylek R, Schürch CM, Chen H, Bjornson-Hooper Z, Christensen SR, Gherardini PF, Bhate SS, Spitzer MH, Fragiadakis GK, Mukherjee N, Kim N, Jiang S, Yo J, Gaudilliere B, Affrime M, Bock B, Hensley SE, Idoyaga J, Aghaeepour N, Kim K, Nolan GP, McIlwain DR. Landscape of coordinated immune responses to H1N1 challenge in humans. The Journal of clinical investigation 2020. PMID: 33044226


  30. Combes AJ, Courau T, Kuhn NF, Hu KH, Ray A, Chen WS, Cleary SJ, Chew NW, Kushnoor D, Reeder GC, Shen A, Tsui J, Hiam-Galvez KJ, Muñoz-Sandoval P, Zhu WS, Lee DS, Sun Y, You R, Magnen M, Rodriguez L, Leligdowicz A, Zamecnik CR, Loudermilk RP, Wilson MR, Ye CJ, Fragiadakis GK, Looney MR, Chan V, Ward A, Carrillo S, Matthay M, Erle DJ, Woodruff PG, Langelier C, Kangelaris K, Hendrickson CM, Calfee C, Rao AA, Krummel MF. Global Absence and Targeting of Protective Immune States in Severe COVID-19. bioRxiv : the preprint server for biology 2020. PMID: 33140050


  31. Krummel M, Combes A, Courau T, Kuhn N, Hu K, Ray A, Chen W, Cleary S, Chew N, Kushnoor D, Reeder G, Shen A, Tsui J, Hiam K, Sandoval PM, Zhu W, Lee D, Sun Y, You R, Magnen M, Rodriguez L, Leligdowicz A, Zamecnik C, Loudermilk R, Wilson M, Ye C, Fragiadakis G, Looney M, Chan V, Ward A, Carrillo S, Matthay M, Erle D, Woodruff P, Langelier C, Kangelaris K, Hendrickson C, Calfee C, Rao A. Global Absence and Targeting of Protective Immune States in Severe COVID-19. Research square 2020. PMID: 33140041


  32. Fragiadakis GK, Wastyk HC, Robinson JL, Sonnenburg ED, Sonnenburg JL, Gardner CD. Long-term dietary intervention reveals resilience of the gut microbiota despite changes in diet and weight. The American journal of clinical nutrition 2020. PMID: 32186326


  33. Ko ME, Williams CM, Fread KI, Goggin SM, Rustagi RS, Fragiadakis GK, Nolan GP, Zunder ER. FLOW-MAP: a graph-based, force-directed layout algorithm for trajectory mapping in single-cell time course datasets. Nature protocols 2020. PMID: 31932774


  34. Bongen E, Lucian H, Khatri A, Fragiadakis GK, Bjornson ZB, Nolan GP, Utz PJ, Khatri P. Sex Differences in the Blood Transcriptome Identify Robust Changes in Immune Cell Proportions with Aging and Influenza Infection. Cell reports 2019. PMID: 31722210


  35. Spencer SP, Fragiadakis GK, Sonnenburg JL. Pursuing Human-Relevant Gut Microbiota-Immune Interactions. Volume 51 of Issue 2. 2019. PMID: 31433970


  36. Aghaeepour N, Simonds EF, Knapp DJHF, Bruggner RV, Sachs K, Culos A, Gherardini PF, Samusik N, Fragiadakis GK, Bendall SC, Gaudilliere B, Angst MS, Eaves CJ, Weiss WA, Fantl WJ, Nolan GP. GateFinder: projection-based gating strategy optimization for flow and mass cytometry. Volume 34 of Issue 23. 2018. PMID: 29850785


  37. Jha AR, Davenport ER, Gautam Y, Bhandari D, Tandukar S, Ng KM, Fragiadakis GK, Holmes S, Gautam GP, Leach J, Sherchand JB, Bustamante CD, Sonnenburg JL. Gut microbiome transition across a lifestyle gradient in Himalaya. Volume 16 of Issue 11. 2018. PMID: 30439937


  38. Fragiadakis GK, Smits SA, Sonnenburg ED, Van Treuren W, Reid G, Knight R, Manjurano A, Changalucha J, Dominguez-Bello MG, Leach J, Sonnenburg JL. Links between environment, diet, and the hunter-gatherer microbiome. Volume 10 of Issue 2. 2018. PMID: 30118385


  39. Blazkova J, Gupta S, Liu Y, Gaudilliere B, Ganio EA, Bolen CR, Saar-Dover R, Fragiadakis GK, Angst MS, Hasni S, Aghaeepour N, Stevenson D, Baldwin N, Anguiano E, Chaussabel D, Altman MC, Kaplan MJ, Davis MM, Furman D. Multicenter Systems Analysis of Human Blood Reveals Immature Neutrophils in Males and During Pregnancy. Volume 198 of Issue 6. Journal of immunology (Baltimore, Md. : 1950) 2017. PMID: 28179497


  40. Furman D, Chang J, Lartigue L, Bolen CR, Haddad F, Gaudilliere B, Ganio EA, Fragiadakis GK, Spitzer MH, Douchet I, Daburon S, Moreau JF, Nolan GP, Blanco P, Déchanet-Merville J, Dekker CL, Jojic V, Kuo CJ, Davis MM, Faustin B. Expression of specific inflammasome gene modules stratifies older individuals into two extreme clinical and immunological states. Volume 23 of Issue 2. Nature medicine 2017. PMID: 28092664


  41. Fragiadakis GK, Baca QJ, Gherardini PF, Ganio EA, Gaudilliere DK, Tingle M, Lancero HL, McNeil LS, Spitzer MH, Wong RJ, Shaw GM, Darmstadt GL, Sylvester KG, Winn VD, Carvalho B, Lewis DB, Stevenson DK, Nolan GP, Aghaeepour N, Angst MS, Gaudilliere BL. Mapping the Fetomaternal Peripheral Immune System at Term Pregnancy. Volume 197 of Issue 11. Journal of immunology (Baltimore, Md. : 1950) 2016. PMID: 27793998


  42. Sogi KM, Holsclaw CM, Fragiadakis GK, Nomura DK, Leary JA, Bertozzi CR. Biosynthesis and Regulation of Sulfomenaquinone, a Metabolite Associated with Virulence in Mycobacterium tuberculosis. Volume 2 of Issue 11. 2016. PMID: 27933784


  43. Angst MS, Fragiadakis GK, Gaudillière B, Aghaeepour N, Nolan GP. In Reply. Volume 124 of Issue 6. 2016. PMID: 27187126


  44. Fragiadakis GK, Gaudillière B, Ganio EA, Aghaeepour N, Tingle M, Nolan GP, Angst MS. Patient-specific Immune States before Surgery Are Strong Correlates of Surgical Recovery. Volume 123 of Issue 6. 2015. PMID: 26655308


  45. Lichtman JS, Alsentzer E, Jaffe M, Sprockett D, Masutani E, Ikwa E, Fragiadakis GK, Clifford D, Huang BE, Sonnenburg JL, Huang KC, Elias JE. The effect of microbial colonization on the host proteome varies by gastrointestinal location. Volume 10 of Issue 5. The ISME journal 2015. PMID: 26574685


  46. Gaudillière B, Ganio EA, Tingle M, Lancero HL, Fragiadakis GK, Baca QJ, Aghaeepour N, Wong RJ, Quaintance C, El-Sayed YY, Shaw GM, Lewis DB, Stevenson DK, Nolan GP, Angst MS. Implementing Mass Cytometry at the Bedside to Study the Immunological Basis of Human Diseases: Distinctive Immune Features in Patients with a History of Term or Preterm Birth. Volume 87 of Issue 9. 2015. PMID: 26190063


  47. Spitzer MH, Gherardini PF, Fragiadakis GK, Bhattacharya N, Yuan RT, Hotson AN, Finck R, Carmi Y, Zunder ER, Fantl WJ, Bendall SC, Engleman EG, Nolan GP. IMMUNOLOGY. An interactive reference framework for modeling a dynamic immune system. Volume 349 of Issue 6244. 2015. PMID: 26160952


  48. Behbehani GK, Thom C, Zunder ER, Finck R, Gaudilliere B, Fragiadakis GK, Fantl WJ, Nolan GP. Transient partial permeabilization with saponin enables cellular barcoding prior to surface marker staining. Volume 85 of Issue 12. 2014. PMID: 25274027


  49. Gaudillière B, Fragiadakis GK, Bruggner RV, Nicolau M, Finck R, Tingle M, Silva J, Ganio EA, Yeh CG, Maloney WJ, Huddleston JI, Goodman SB, Davis MM, Bendall SC, Fantl WJ, Angst MS, Nolan GP. Clinical recovery from surgery correlates with single-cell immune signatures. Volume 6 of Issue 255. Science translational medicine 2014. PMID: 25253674