Trygve Bakken, M.D., Ph.D.
Assistant Investigator
Trygve Bakken joined the Allen Institute in 2013 to develop computational tools to study gene expression dynamics during primate cortical development. He currently co-leads an effort to define the cellular components of adult human brain circuits using high-throughput, single nucleus RNA-sequencing and to compare these cell types across human individuals and other species. Previously, he completed an M.D. and a Ph.D. in Neuroscience at the University of California, San Diego where he identified genomic variation shaping human brain morphology and a developmental scaling rule optimizing conduction velocities in the fish visual system under the co-mentorship of Charles Stevens and Nicholas Schork. Prior to that, he completed an M.Sc. in Philosophy and History of Science at the London School of Economics and a B.A. in Physics and Philosophy at Yale University.
Research
Research Interests
The human brain is a complex circuit composed of over 170 billion neuronal and non-neuronal cells that have diverse molecular profiles, connectivity, and firing properties. I co-lead a team to characterize cellular diversity in human brain using high-throughput, unbiased single nucleus RNA-sequencing. This technology provides a global snapshot of transcribed genes that collectively shape the identity of a cell. I am interested in developing robust computational tools to group cells based on shared identity and to compare these cell types across brain regions, human individuals, and species. We are investigating whether there is a canonical neocortical circuit with shared cellular components and the relationship between the mature identity and developmental origin of cell types. We are examining how cell types vary in the human population due to many variables, including genomic variation and disease state. We are testing whether cell type function can be predicted from the expression of well-characterized gene families, such as voltage-gated ion channels and neurotransmitter receptors. Finally, we are quantifying the conservation of human and mouse brain circuits and comparing expression of homologous cell types to better understand the limitations of the rodent as a model system for probing human brain function. In the future, profiling cellular diversity in a much broader range of species will refine the core transcriptomic identity of conserved cell types and will enable comparisons between species traits and the emergence of novel cell types and divergent expression.
Expertise
- Molecular Neuroscience
- Genomics
- Comparative Biology
- Informatics
Research Programs
- Human Cell Types
Selected Publications View Publications
Proceedings of the National Academy of Sciences
June 10, 2020
Huang AY, Li P, Rodin RE, Kim SN, Dou Y, Kenny CJ, Akula SK, Hodge RD, Bakken TE, Miller JA, Lein ES, Park PJ, Lee EA, Walsh CA
PLoS One
September 4, 2019
Weed N, Bakken T, Graddis N, Gouwens N, Millman D, Hawrylycz M, Waters J
Conserved cell types with divergent features in human versus mouse cortex
Nature
August 21, 2019
Hodge RD, Bakken TE, Miller JA, Smith KA, Barkan ER, Graybuck LT, Close JL, Long B, Johansen N, Penn O, Yao Z, Eggermont J, Höllt T, Levi BP, Shehata SI, Aevermann B, Beller A, Bertagnolli D, Brouner K, Casper T, Cobbs C, Dalley R, Dee N, Ding SL, Ellenbogen RG, Fong O, Garren E, Goldy J, Gwinn RP, Hirschstein D, Keene CD, Keshk M, Ko AL, Lathia K, Mahfouz A, Maltzer Z, McGraw M, Nguyen TN, Nyhus J, Ojemann JG, Oldre A, Parry S, Reynolds S, Rimorin C, Shapovalova NV, Somasundaram S, Szafer A, Thomsen ER, Tieu M, Quon G, Scheuermann RH, Yuste R, Sunkin SM, Lelieveldt B, Feng D, Ng L, Bernard A, Hawrylycz M, Phillips JW, Tasic B, Zeng H, Jones AR, Koch C, Lein ES
New insights into the development of the human cerebral cortex
Journal of Anatomy
August 2, 2019
Molnár Z, Clowry GJ, Šestan N, Alzu'bi A, Bakken T, Hevner RF, Hüppi PS, Kostović I, Rakic P, Anton ES, Edwards D, Garcez P, Hoerder-Suabedissen A, Kriegstein A
Epigenetic landscape and AAV targeting of human neocortical cell classes
bioRxiv
February 19, 2019
Mich JK, Hess EE, Graybuck LT, Somasundaram S, Miller JA, Ding Y, Shapovalova NV, Fong O, Yao S, Mortrud M, Chong P, Bertagnolli D, Goldy J, Casper T, Kroll M, Hodge RD, Bakken TE, Yao Z, Dee N, Cetin A, Smith KA, Gwinn RP, Cobbs C, Ko AL, Ojemann JG, Keene CD, Silbergeld DL, Gradinaru V, Sunkin SM, Zeng H, Lein ES, Tasic B, Ting JT, Levi BP
Transcriptomic evidence for dense peptidergic neuromodulation networks in mouse cortex
bioRxiv
January 13, 2019
Smith SJ, Sumbul U, Graybuck LT, Collman F, Sharmishtaa S, Gala R, Gliko O, Elabbady L, Miller J, Bakken T, Yao Z, Lein ES, Zeng H, Tasic B, Hawrylycz M
Sex-Based Analysis of De Novo Variants in Neurodevelopmental Disorders
American Journal of Human Genetics
November 25, 2019
Turner TN, Wilfert AB, Bakken TE, Bernier RA, Pepper MR, Zhang Z, Torene RI, Retterer K, Eichler EE
Single-cell transcriptomic evidence for dense intracortical neuropeptide networks.
eLife
November 11, 2019
Smith SJ, Sümbül U, Graybuck LT, Collman F, Seshamani S, Gala R, Gliko O, Elabbady L, Miller JA, Bakken TE, Rossier J, Yao Z, Lein E, Zeng H, Tasic B, Hawrylycz M
Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type
Nature Neuroscience
August 27, 2018
Boldog E, Bakken TE, Hodge RD, Novotny M, Aevermann BD, Baka J, Bordé S, Jennie L. Close, Diez-Fuertes F, Ding SL, Faragó N, Kocsis AK, Kovács B, Maltzer Z, McCorrison JM, Miller JA, Molnár G, Oláh G, Ozsvár A, Rózsa M, Shehata SI, Smith KA, Sunkin SM, Tran DN, Venepally P, Wall A, Puskás LG, Barzó P, Steemers FJ, Schork NJ, Scheuermann RH, Lasken RS, Lein ES, Tamás G
Genetic identification of brain cell types underlying schizophrenia
Nature Genetics
May 21, 2018
Skene NG, Bryois J, Bakken TE, Breen G, Crowley JJ, Gaspar HA, Giusti-Rodriguez P, Hodge RD, Miller JA, Muñoz-Manchado A, O'Donovan MC, Owen MJ, Pardiñas AF, Ryge J, Walters JTR, Linnarsson S, Lein ES, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Sullivan PS, Hjerling-Leffler J
Cell type discovery using single-cell transcriptomics: implications for ontological representation
Human Molecular Genetics
May 1, 2018
Aevermann BD, Novotny M, Bakken T, Miller JA, Diehl AD, Osumi-Sutherland D, Lasken RS, Lein ES, Scheuermann RH
Single-nucleus and single-cell transcriptomes compared in matched cortical cell types
PLoS One
December 26, 2018
Bakken TE, Hodge RD, Miller JA, Yao Z, Nguyen TN, Aevermann B, Barkan E, Bertagnolli D, Casper T, Dee N, Garren E, Goldy J, Graybuck LT, Kroll M, Lasken RS, Lathia K, Parry S, Rimorin C, Scheuermann RH, Schork NJ, Shehata SI, Tieu M, Phillips JW, Bernard A, Smith KA, Zeng H, Lein ES, Tasic B
Neurodevelopmental disease genes implicated by de novo mutation and copy number variation morbidity
Nature Genetics
December 17, 2018
Coe BP, Stessman HAF, Sulovari A, Geisheker MR, Bakken TE, Lake AM, Dougherty JD, Lein ES, Hormozdiari F, Bernier RA, Eichler EE
Neuron
November 1, 2018
Kalmbach BE, Buchin A, Long B, Close J, Nandi A, Miller JA, Bakken TE, Hodge RD, Chong P, de Frates R, Dai K, Maltzer Z, Nicovich PR, Keene CD, Silbergeld DL, Gwinn RP, Cobbs C, Ko AL, Ojemann JG, Koch C, Anastassiou CA, Lein ES, Ting JT
Shared and distinct transcriptomic cell types across neocortical areas
Nature
October 31, 2018
Tasic B, Yao Z, Graybuck LT, Smith KA, Nguyen TN, Bertagnolli D, Goldy J, Garren E, Economo MN, Viswanathan S, Penn O, Bakken T, Menon V, Miller J, Fong O, Hirokawa KE, Lathia K, Rimorin C, Tieu M, Larsen R, Casper T, Barkan E, Kroll M, Parry S, Shapovalova NV, Hirschstein D, Pendergraft J, Sullivan HA, Kim TK, Szafer A, Dee N, Groblewski P, Wickersham I, Cetin A, Harris JA, Levi BP, Sunkin SM, Madisen L, Daigle TL, Looger L, Bernard A, Phillips J, Lein E, Hawrylycz M, Svoboda K, Jones AR, Koch C, Zeng H
The Markov link method: a nonparametric approach to combine observations from multiple experiments
bioRxiv
October 30, 2018
Loper J, Bakken T, Sumbul U, Murphy G, Zeng H, Bleib D, Paninski L
A comprehensive transcriptional map of primate brain development
Nature
July 13, 2016
Bakken TE, Miller JA, Ding SL, Sunkin SM, Smith KA, Ng L, Szafer A, Dalley RA, Royall JJ, Lemon T, Shapouri S, Aiona K, Arnold J, Bennett JL, Bertagnolli D, Bickley K, Boe A, Brouner K, Butler S, Byrnes E, Caldejon S, Carey A, Cate S, Chapin M, Chen J, Dee N, Desta T, Dolbeare TA, Dotson N, Ebbert A, Fulfs E, Gee G, Gilbert TL, Goldy J, Gourley L, Gregor B, Gu G, Hall J, Haradon Z, Haynor DR, Hejazinia N, Hoerder-Suabedissen A, Howard R, Jochim J, Kinnunen M, Kriedberg A, Kuan CL, Lau C, Lee CK, Lee F, Luong L, Mastan N, May R, Melchor J, Mosqueda N, Mott E, Ngo K, Nyhus J, Oldre A, Olson E, P
The complete genome sequence of a Neanderthal from the Altai Mountains
Nature
January 2, 2014
Prüfer K, Racimo F, Patterson N, Jay F, Sankararaman S, Sawyer S, Heinze A, Renaud G, Sudmant PH, de Filippo C, Li H, Mallick S, Dannemann M, Fu Q, Kircher M, Kuhlwilm M, Lachmann M, Meyer M, Ongyerth M, Siebauer M, Theunert C, Tandon A, Moorjani P, Pickrell J, Mullikin JC, Vohr SH, Green RE, Hellmann I, Johnson PL, Blanche H, Cann H, Kitzman JO, Shendure J, Eichler EE, Lein ES, Bakken TE, Golovanova LV, Doronichev VB, Shunkov MV, Derevianko AP, Viola B, Slatkin M, Reich D, Kelsho J, Pääbo S
PNAS
March 2012
Bakken TE, Roddey JC, Djurovic S, Akshoomoff N, Amaral DG, et al
Visual system scaling in teleost fish
Journal of Comparative Neurology
January 2012
Bakken TE, Stevens CF
Association of genetic variants on 15q12 with cortical thickness and cognition in schizophrenia
Archives of General Psychiatry
August 2011
Bakken TE, Bloss CS, Roddey JC, Joyner AH, Rimol LM, et al
A geographic cline of skull and brain morphology among individuals of European Ancestry
Human Heredity
2011
Bakken TE, Dale AM, Schork NJ