Team

Staff Profiles

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

Single-cell and single-nucleus RNA-seq uncovers shared and distinct axes of variation in dorsal LGN neurons in mice, non-human primates, and humans

eLife
September 2, 2021

Bakken TE, van Velthoven CT, Menon V, Hodge RD, Yao Z, Nguyen TN, Graybuck LT, Horwitz GD, Bertagnolli D, Goldy J, Yanny AM, Garren E, Parry S, Casper T, Shehata SI, Barkan ER, Szafer A, Levi BP, Dee N, Smith KA, Sunkin SM, Bernard A, Phillips J, Hawrylycz MJ, Koch C, Murphy GJ, Lein E, Zeng H, Tasic B

Signature morpho-electric, transcriptomic, and dendritic properties of human layer 5 neocortical pyramidal neurons

Neuron
September 15, 2021

Kalmbach BE, Hodge RD, Jorstad NL, Owen S, de Frates R, Yanny AM, Dalley R, Mallory M, Graybuck LT, Radaelli C, Keene CD, Gwinn RP, Silbergeld DL, Cobbs C, Ojemann JG, Ko AL, Patel AP, Ellenbogen RG, Bakken TE, Daigle TL, Dee N, Lee BR, McGraw M, Nicovich PR, Smith K, Sorensen SA, Tasic B, Zeng H, Koch C, Lein ES, Ting JT

Recent ultra-rare inherited variants implicate new autism candidate risk genes

Nature Genetics
August 2021

Wilfert AB, Turner TN, Murali SC, Hsieh P, Sulovari A, Wang T, Coe BP, Guo H, Hoekzema K, Bakken TE, Winterkorn LH, Evani US, Byrska-Bishop M, Earl RK, Bernier RA; SPARK Consortium, Zody MC, Eichler EE.

A machine learning method for the discovery of minimum marker gene combinations for cell-type identification from single-cell RNA sequencing

Genome Research
June 4, 2021

Aevermann BD, Zhang Y, Novotny M, Keshk M, Bakken TE, Miller JA, Hodge RD, Lelieveldt B, Lein ES, Scheuermann RH.

Comparative cellular analysis of motor cortex in human, marmoset and mouse

Nature
October 6, 2021

Bakken TE, Jorstad NL, Hu Q, Lake BB, Tian W, Kalmbach BE, Crow M, Hodge RD, Krienen FM, Sorensen SA, Eggermont J, Yao Z, Aevermann BD, Aldridge AI, Bartlett A, Bertagnolli D, Casper T, Castanon RG, Crichton K, Daigle TL, Dalley R, Dee N, Dembrow N, Diep D, Ding SL, Dong W, Fang R, Fischer S, Goldman M, Goldy J, Graybuck LT, Herb BR, Hou X, Kancherla J, Kroll M, Lathia K, van Lew B, Li YE, Liu CS, Liu H, Lucero JD, Mahurkar A, McMillen D, Miller JA, Moussa M, Nery JR, Nicovich PR, Niu SY, Orvis J, Osteen JK, Owen S, Palmer CR, Pham T, Plongthongkum N, Poirion O, Reed NM, Rimorin C, Rivkin A, Romanow WJ, Sedeño-Cortés AE, Siletti K, Somasundaram S, Sulc J, Tieu M, Torkelson A, Tung H, Wang X, Xie F, Yanny AM, Zhang R, Ament SA, Behrens MM, Bravo HC, Chun J, Dobin A, Gillis J, Hertzano R, Hof PR, Höllt T, Horwitz GD, Keene CD, Kharchenko PV, Ko AL, Lelieveldt BP, Luo C, Mukamel EA, Pinto-Duarte A, Preissl S, Regev A, Ren B, Scheuermann RH, Smith K, Spain WJ, White OR, Koch C, Hawrylycz M, Tasic B, Macosko EZ, McCarroll SA, Ting JT, Zeng H, Zhang K, Feng G, Ecker JR, Linnarsson S, Lein ES

Human neocortical expansion involves glutamatergic neuron diversification

Nature
October 6, 2021

Berg J, Sorensen SA, Ting JT, Miller JA, Chartrand T, Buchin A, Bakken TE, Budzillo A, Dee N, Ding SL, Gouwens NW, Hodge RD, Kalmbach B, Lee C, Lee BR, Alfiler L, Baker K, Barkan E, Beller A, Berry K, Bertagnolli D, Bickley K, Bomben J, Braun T, Brouner K, Casper T, Chong P, Crichton K, Dalley R, de Frates R, Desta T, Lee SD, D'Orazi F, Dotson N, Egdorf T, Enstrom R, Farrell C, Feng D, Fong O, Furdan S, Galakhova AA, Gamlin C, Gary A, Glandon A, Goldy J, Gorham M, Goriounova NA, Gratiy S, Graybuck L, Gu H, Hadley K, Hansen N, Heistek TS, Henry AM, Heyer DB, Hill D, Hill C, Hupp M, Jarsky T, Kebede S, Keene L, Kim L, Kim MH, Kroll M, Latimer C, Levi BP, Link KE, Mallory M, Mann R, Marshall D, Maxwell M, McGraw M, McMillen D, Melief E, Mertens EJ, Mezei L, Mihut N, Mok S, Molnar G, Mukora A, Ng L, Ngo K, Nicovich PR, Nyhus J, Olah G, Oldre A, Omstead V, Ozsvar A, Park D, Peng H, Pham T, Pom CA, Potekhina L, Rajanbabu R, Ransford S, Reid D, Rimorin C, Ruiz A, Sandman D, Sulc J, Sunkin SM, Szafer A, Szemenyei V, Thomsen ER, Tieu M, Torkelson A, Trinh J, Tung H, Wakeman W, Waleboer F, Ward K, Wilbers R, Williams G, Yao Z, Yoon JG, Anastassiou C, Arkhipov A, Barzo P, Bernard A, Cobbs C, de Witt Hamer PC, Ellenbogen RG, Esposito L, Ferreira M, Gwinn RP, Hawrylycz MJ, Hof PR, Idema S, Jones AR, Keene CD, Ko AL, Murphy GJ, Ng L, Ojemann JG, Patel AP, Phillips JW, Silbergeld DL, Smith K, Tasic B, Yuste R, Segev I, de Kock CPJ, Mansvelder HD, Tamas G, Zeng H, Koch C, Lein ES

A multimodal cell census and atlas of the mammalian primary motor cortex

Nature
October 6, 2021

BRAIN Initiative Cell Census Network (BICCN)

Parallel RNA and DNA analysis after deep sequencing (PRDD-seq) reveals cell type-specific lineage patterns in human brain

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

Common cell type nomenclature for the mammalian brain

eLife
December 29, 2020

Miller JA, Gouwens NW, Tasic B, Collman F, van Velthoven CT, Bakken TE, Hawrylycz MJ, Zeng H, Lein ES, Bernard A.

FR-Match: robust matching of cell type clusters from single cell RNA sequencing data using the Friedman-Rafsky non-parametric test

Briefings in Bioinformatics
November 30, 2020

Zhang Y, Aevermann BD, Bakken TE, Miller JA, Hodge RD, Lein ES, Scheuermann RH.

Identification of genetic markers for cortical areas using a Random Forest classification routine and the Allen Mouse Brain Atlas

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

h-Channels Contribute to Divergent Intrinsic Membrane Properties of Supragranular Pyramidal Neurons in Human versus Mouse Cerebral Cortex

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

Association of common genetic variants in GPCPD1 with scaling of visual cortical surface area in humans

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