How Artificial Intelligence is re-engineering protein engineering
Jennifer Listgarten and Hanlun Jiang
Science April 2026
(official link,
pdf)
Leveraging Discrete Function Decomposability for Scientific Design
James C. Bowden, Sergey Levine, Jennifer Listgarten
accepted at ICML 2026
(pre-print)
Structural ontogeny of protein-protein interactions
Aerin Yang*, Hanlun Jiang*, Kevin M. Jude*, Deniz Akpinaroglu, Stephan Allenspach*,
Alex Jie Li, James Bowden, Carla Patricia Perez, Liu Liu, Po-Ssu Huang,
Tanja Kortemme, Jennifer Listgarten, K. Christopher Garcia
Science 2026
(official link,
alternate link )
*(equal contributions), ((co-corresponding)
Write and Read: Harnessing Synthetic DNA Modifications for Nanopore Sequencing
Uri Bertocchi, Assaf Grunwald, Gal Goldner, Eliran Eitan, Sigal Avraham, Shani Dvir, Jasline Deek, Yael Michaeli, Brian Yao, Jennifer Listgarten, Jared T. Simpson, Winston Timp, Yuval Ebenstein*
ACS Nano 2025
(link),
Editor's Choice award
ProteinGuide: On-the-fly property guidance for protein sequence generative models
Junhao Xiong*, Hunter Nisonoff*, Maria Lukarska*, Ishan Gaur, Luke M. Oltrogge, David F. Savage+, Jennifer Listgarten+
arXiv (major update Jan 2026)
(link)
*(equal contributions), +(co-corresponding)
Unlocking Guidance for Discrete State-Space Diffusion and Flow Models
{Hunter Nisonoff*, Junhao Xiong*, Stephan Allenspach*}, Jennifer Listgarten
ICLR 2025
(link)
*(equal contributions)
Learning antibody sequence constraints from allelic inclusion
Milind Jagota, Chloe Hsu, Thomas Mazumder, Kevin Sung, William S DeWitt, Jennifer Listgarten, Frederick A Matsen IV, Chun Jimmie Ye, Yun S Song
bioRxiv
(link)
2024
*(equal contributions)
Computationally guided AAV engineering for enhanced gene delivery
Jingxuan Guo, Li F Lin, Sydney V Oraskovich, Julio A Rivera de Jes�s, Jennifer Listgarten, David V Schaffer
Trends in Biochemical Sciences 2024
(link)
GENTANGLE: integrated computational design of gene entanglements
Jose Manuel Mart�, Chloe Hsu, Charlotte Rochereau, Chenling Xu, Tomasz Blazejewski, Hunter Nisonoff, Sean P Leonard, Christina S Kang-Yun, Jennifer Chlebek, Dante P Ricci, Dan Park, Harris Wang, Jennifer Listgarten, Yongqin Jiao, Jonathan E Allen
Bioinformatics 2024
(link)
Generative models for protein structures and sequences
Chloe Hsu, Clara Fannjiang, Jennifer Listgarten
Nature Biotechnology 2024
(link)
and a freely available copy here.
The perpetual motion machine of AI-generated data and the distraction of "ChatGPT as scientist"
Jennifer Listgarten
Nature Biotechnology 2024
(link)
and a freely available version here,
and a talk
at the 2024 National Academy of Sciences annual meeting.
Optimal trade-off control in machine learning-based library design, with application to adeno-associated virus (AAV) for gene therapy
D Zhu*, DH Brookes*, A Busia*, A Carneiro, C Fannjiang, G Popova, D Shin, KC Donohue,, LF Lin, ZM Miller, ER Williams, EF Chang, TJ Nowakowski, J Listgarten*, DV Schaffer*
(*equal contributions, corresponding)
Science Advances 2024
(paper link)
Effective training of nanopore callers for epigenetic marks with limited labelled data
Brian Yao, Chloe Hsu, Gal Goldner, Yael Michaeli, Yuval Ebenstein, Jennifer Listgarten
Open Biology 2024,
(paper link)
Is novelty predictable?
Clara Fannjiang and Jennifer Listgarten
Cold Spring Harbor Perspectives in Biology 2023
(paper link),
similar version also available on arXiv).
MBE: model-based enrichment estimation and prediction for differential sequencing data
Akosua Busia and Jennifer Listgarten
Genome Research 2023,
(paper link)
Coherent Blending of Biophysics-Based Knowledge with Bayesian Neural Networks for Robust Protein Property Prediction
Hunter Nisonoff, Yixin Wang, Jennifer Listgarten
ACS Synth. Biol. 2023 (Editor's Choice)
(paper link)
Conformal Prediction under Feedback Covariate Shift for Biomolecular Design
Clara Fannjiang, Stephen Bates, Anastasios Angelopoulos, Jennifer Listgarten, and Michael I. Jordan
PNAS 2022,
(paper link)
On the sparsity of fitness functions and implications for learning
David H Brookes, Amirali Aghazadeh, Jennifer Listgarten
PNAS 2022,
(paper link)
Learning protein fitness models from evolutionary and assay-labeled data
Chloe Hsu, Hunter Nisonoff, Clara Fannjiang, Jennifer Listgarten
Nature Biotechnology 2022
(paper)
Epistatic Net allows the sparse spectral regularization of deep neural networks for inferring fitness functions
Amirali Aghazadeh, Hunter Nisonoff, Ocal, Yijie Huang, O. Ozan Koyluoglu, Jennifer Listgarten, Kannan Ramchandran
Nature Communications 2021,
(paper link)
Autofocused oracles for model-based design
Clara Fannjiang and Jennifer Listgarten
NeurIPS 2020,
(paper link)
Rethinking drug design in the artificial intelligence era
P Schneider, WP Walters, AT Plowright, N Sieroka,
J Listgarten, RA Goodnow Jr., J Fisher,
JM Jansen, JS Duca, TS Rush, M Zentgraf,
JE Hill, E Krutoholow, M Kohler, J Blaney,
K Funatsu, C Luebkemann and G Schneider
in Nature Reviews Drug Discovery
2019
(paper link)
A view of Estimation of Distribution Algorithms through the lens of Expectation-Maximization
David H. Brookes, Akosua Busia, Clara Fannjiang, Kevin Murphy and Jennifer Listgarten
in Proceedings of GECCO 2020
(here
, extended version
here)
Conditioning by adaptive sampling for robust design
David H. Brookes, Hahnbeom Park and Jennifer Listgarten
accepted at ICML
2019
(paper link, arXiv version is most up-to-date)
(5% acceptance rate for 20 min. oral presentation)
Design by adaptive sampling
David Brookes and Jennifer Listgarten
NeurIPS Workshop on Machine Learning for Molecules and Materials
2018
(paper link)
Gaussian Process Prior Variational Autoencoders
Francesco Paolo Casale, Adrian V Dalca, Luca Saglietti,
Jennifer Listgarten, Nicolo Fusi
in NeurIPS
2018
(paper link)
Predicting off-target effects for end-to-end CRISPR guide design
J Listgarten, M Weinstein, B Kleinstiver, AA Sousa, JK Joung, J Crawford, K Gao, M Elibol, L Hoang, J Doench, N Fusi
(equal contributions and corresponding)
Nature Biomedical Engineering
(2018)
(paper link)
Associated tools and resources available
here.
Orthologous CRISPR-Cas9 for Combinatorial Genetic Screens
F Najm*, C Strand*, K Donovan*, M Hegde*, KR. Sanson*, EW Vaimberg, ME Sullender, E Hartenian, N Fusi,
J. Listgarten, ST Younger*, BE Bernstein**, DE Root**, JG Doench**
Nature Biotechnology
(2018)
(paper link)
(*equal contributions, **corresponding)
Identifying gene expression modules that define human cell fates
I Germanguz, J Listgarten, A Solomon, X Gaeta, WE Lowry
(equal contributions)
Stem Cell Research
(2016,, in press)
Leveraging Non-Linear Genetic Effects on Functional Traits for GWAS
Nicolo Fusi and Jennifer Listgarten
RECOMB Proceedings (in Lecture Notes in Computer Science)
2016
(pdf)
Optimized sgRNA design to maximize activity and minimize off-target effects for genetic screens with CRISPR-Cas9
JG Doench*, N Fusi*, M Sullender*, M Hegde*, EW Vaimberg*, KF Donovan, I Smith, Z Tothova,
C Wilen , R Orchard , HW Virgin, J Listgarten*, DE Root
Nature Biotechnology Jan 2016
doi:10.1038/nbt.3437
(*equal contributions, corresponding)
A pre-print of just the computational aspects of this paper is available
on
bioRxiv
Source code and prediction server available from here:
here.
[Microsoft Research blog post]
[Broad Institute blog post]
In Silico Predictive Modeling of CRISPR/Cas9 guide efficiency
Nicolo Fusi, Ian Smith, John Doench, Jennifer Listgarten
bioRxiv, dx.doi.org/10.1101/021568
2015 (
preprint
)
This pre-print has been largely (though not entirely) absorbed into the
Nature Biotechnology paper above.
Further Improvements to Linear Mixed Models for Genome-Wide Association Studies
Chris Widmer, Christoph. Lippert, Omer Weissbrod, Nicolo Fusi, Carl Kadie, Bob Davidson, Jennifer Listgarten and D. Heckerman
Scientific Reports,
Nov. 2014
(open access)
let-7 miRNAs Can Act through Notch to Regulate Human Gliogenesis
Patterson M, Gaeta X, Loo K, Edwards M, Smale S, Cinkornpumin J, Xie Y, Listgarten J, Azghadi S, Douglass SM, Pellegrini M, Lowry WE.
Stem Cell Reports
2014,
doi: 10.1016/j.stemcr.2014.08.015
(open access)
Personalized Medicine: From Genotypes, Molecular Phenotypes and the Quantified Self, Toward Improved Medicine
Joel Dudley, Jennifer Listgarten, Oliver Stegle, Steven Brenner, Leopold Parts
Proceedings of the Pacific Symposium on Biocomputing
2015
(pdf)
Greater power and computational efficiency for kernel-based association testing of sets of genetic variants
C. Lippert, J. Xiang, D. Horta, C. Widmer, C. Kadie, D. Heckerman, Jennifer Listgarten
Bioinformatics
2014,
doi: 10.1093/bioinformatics/btu504
(open access)
Epigenome-wide association studies without the need for cell-type composition
James Zou, Christoph Lippert, David Heckerman, Martin Aryee, Jennifer Listgarten
Nature Methods, 309-311 (2014)
(journal link)
Python software available from here, and
R software available from here.
Corrigendum: Supp. Figure 1 was not run with filters as described in the paper, but without any filters. We have contacted the journal to post this correction.
Personalized Medicine: from genotypes and molecular phenotypes toward therapy
Jennifer Listgarten, Oliver Stegle, Quaid Morris, Steven Brenner, Leo Parts
Proceedings of the Pacific Symposium on Biocomputing
2014
A genome-to-genome analysis of associations between human genetic variation, HIV-1 sequence diversity, and viral control.
I. Bartha, J. Carlson, C. Brumme, P. McLaren, Z. Brumme, M. John, D. Haas, J. Martinez-Picado, J. Dalmau, C. López-Galíndez, C. Casado, A. Rauch, H. Günthard, E. Bernasconi, P. Vernazza, T. Klimkait, S. Yerly, S. O’Brien, Jennifer Listgarten, N. Pfeifer, C. Lippert, N. Fusi, Z. Kutalik, T. Allen, Viktor Müller, R. Harrigan, D. Heckerman, A. Telenti, J. Fellay
eLife
(2013) 2:e01123
(journal link)
The benefits of selecting phenotype-specific variants for applications of mixed models in genomics.
C. Lippert,
G. Quon, EY Kang, C. Kadie,
Jennifer Listgarten,
D. Heckerman
(equal contributions)
Scientific Reports
(2013) doi:10.1038/srep01815
(journal link)
FaST-LMM-Select for addressing confounding from spatial structure and rare variants
Jennifer Listgarten, Christoph Lippert, David Heckerman
(equal contributions and corresponding)
Nature Genetics,
45, 470-471 (2013) doi:10.1038/ng.2620
(journal link)
A powerful and efficient set test for genetic markers that handles confounders
Jennifer Listgarten, C. Lippert, EY Kang, J. Xiang, C. Kadie, D. Heckerman
(equal contributions and corresponding)
Bioinformatics
2013,
doi: 10.1093/bioinformatics/btt177
(open access)
Source and executables available
here.
An Exhaustive Epistatic SNP Association Analysis on Expanded Wellcome Trust Data
C. Lippert,
Jennifer Listgarten,
R. Davidson,
S. Baxter,
H. Poon,
C. Kadie,
D. Heckerman,
(equal contributions)
Scientific Reports,
2013,
doi:10.1038/srep01099
Patterns of methylation heritability in a genome-wide analysis of four brain regions
Gerald Quon,
Christoph Lippert,
David Heckerman,
Jennifer Listgarten
Nucleic Acids Research,
2013,
doi: 10.1093/nar/gks1449
The future of genome-based medicine.
Quaid Morris, Steven Brenner, Jennifer Listgarten, Oliver Stegle
Proceedings of the Pacific Symposium on Biocomputing
2013, 16:456-458. doi:10.1142/9789814447973_0046
Correlates of Protective Cellular Immunity Revealed by Analysis
of Population-Level Immune Escape Pathways in HIV-1
J. Carlson,
C. Brumme,
E. Martin,
Jennifer Listgarten,
M. Brockman,
AQ. Le,
C. Chui,
L. Cotton,
D. Knapp,
SA. Riddler,
R. Haubrich,
G. Nelson,
N. Pfeifer,
C. DeZiel,
D. Heckerman,
R. Apps,
M. Carrington,
S. Mallal,
R. Harrigan,
M. John,
Z. Brumme
and the International HIV Adaptation Collaborative
Journal of Virology, Dec. 2012,
86(4)
Co-Operative Additive Effects between HLA Alleles in Control of HIV-1
P. Matthews, Jennifer Listgarten, J.
Carlson, R. Payne, KH Huang, J Frater,
D Goedhals, D Steyn, D van Vuuren, P Paioni,
P Jooste, A Ogwu, R Shapiro, Z Mncube, T
Ndung'u, B Walker, D Heckerman, P
Goulder
(equal contributions)
PLoS One,
2012,
7(10): e47799. doi:10.1371/journal.pone.0047799
Improved linear mixed models for genome-wide association studies
Jennifer Listgarten, C Lippert, CM Kadie, RI Davidson, E Eskin and
D Heckerman
(equal contributions and corresponding)
Nature Methods,
2012,
doi:10.1038/nmeth.2037
Source and executables available
here.
Learning Transcriptional Regulatory Relationships Using Sparse Graphical Models
X Zhang, W Cheng, Jennifer Listgarten, C Kadie, S Huang, W Wang, D Heckerman
PLoS One,
2012,
doi:10.1371/journal.pone.0035762
Widespread Impact of HLA Restriction on Immune Control and Escape Pathways in HIV-1
J. Carlson, Jennifer Listgarten, N Pfeifer, V Tan, Carl Kadie, B Walker, T Ndung'u, R Shapiro, J Frater, Z Brumme, P Goulder and D Heckerman
Journal of Virology,
February 2012,
doi:10.1128/?JVI.06728-11
(abstract,paper)
Personalized Medicine: From Genotype and Molecular Phenotypes Towards Computed Therapy
Oliver Stegle, Frederick P. Roth, Quaid Morris, Jennifer Listgarten
Proceedings of the Pacific Symposium on Biocomputing
2012
FaST Linear Mixed Models for Genome-Wide Association Studies
C Lippert, Jennifer Listgarten, Y Liu, CM Kadie, RI Davidson and D Heckerman
(equal contributions and corresponding)
Nature Methods,
Aug. 2011,
doi:10.1038/nmeth.1681
,
freely available author copy including SI,
Source and executables available
here.
HLA-A*7401-mediated control of HIV viremia is independent of its linkage
disequilibrium with HLA-B*5703.
P. Matthews, E. Adland, J. Listgarten, A. Leslie, N. Mkhwanazi, J. Carlson, M. Harndahl, A. Stryhn, R.
Payne, A. Ogwu, K. Huang, J. Frater, P. Paioni, H. Kloverpris, P.Jooste, D. Goedhals, C. van Vuuren, D.
Steyn, L. Riddell, F. Chen, G. Luzzi, T. Balachandran, T. Ndung'u, S. Buus, M. Carrington, R. Shapiro, D.
Heckerman, and P. Goulder
Journal of Immunology
April 2011,
doi: 10.4049
Correction for Hidden Confounders in the Genetic Analysis of Gene Expression
Jennifer Listgarten, Carl Kadie, Eric Schadt, David Heckerman
Proceedings of the National Academy of Sciences,
September 1, 2010, doi: 10.1073/pnas.1002425107
(paper,
Supplementary Information,
software,
GenomeWeb coverage)
Additive contribution of HLA class I alleles in the immune control of HIV-1 infection
Leslie A, Matthews PC, Listgarten J, Carlson JM, Kadie C, Ndung'u T, Brander C, Coovadia H, Walker BD,
Heckerman D, Goulder PJ
Journal of Virology
, 2010
Rare HLA Drive Additional HIV Evolution Compared to More Frequent Alleles
CM Rousseau, DW Lockhart, Jennifer Listgarten, C Kadie, GH
Learn, DC Nickle, D Heckerman, W Deng, C Brander, T
Ndung'u, H Coovadia, P Goulder, B. Korber, B Walker, J Mullins
AIDS Research and Human Retroviruses
, 2009; 25(3):297-303
In silico resolution of ambiguous HLA typing data
J Listgarten, Z Brumme, C Kadie, G Xiaojiang, B Walker, M
Carrington, P Goulder, D Heckerman,
in ASHI Quarterly, Volume 32, Number 2, 2008
For the public web server tool based on this work,
go
here ;
for .exe and source code (training code not included), go
here.
(pdf)
Statistical resolution of ambiguous HLA typing data.
Jennifer Listgarten, Z Brumme, C Kadie, G Xiaojiang, B Walker, M
Carrington, P Goulder, D Heckerman,
in PLoS Computational Biology, 2008, 4(2):e1000016
For the public web server tool based on this work,
go
here ;
for .exe and source code (training code not included), go
here.
(abstract,
paper,
coverage in the magazine BioInform,
press release)
A statistical framework for modeling HLA-dependent T-cell response data.
Jennifer Listgarten, Nicole Frahm, Carl Kadie, Christian Brander and David
Heckerman,
PLoS Computational Biology, 2007, 3(10):e188
Web tool, executable and source code available
here, under "HLA Assignment"
(abstract, paper,
press release)
Extensive HLA class I allele promiscuity among viral CTL epitopes.
N. Frahm, K. Yusim, T. Suscovich, S. Adams, J. Sidney, P. Hraber, H. Hewitt, CH. Linde, D. Kavanagh, T.
Woodberry, L. Henry, K. Faircloth, J. Listgarten, C. Kadie, N. Jojic, K. Sango, N. Brown, E. Pae, M. Zaman, F.
Bihl, A. Khatri, M. John, S. Mallal, F. Marincola, B. Walker, A. Sette, D. Heckerman, B. Korber, C. Brander
European Journal of Immunology, 2007 37(9):2419-2433.
See paper above for code/tools used in this paper.
(abstract)
Evidence that dysregulated DNA mismatch repair characterizes human
non-melanoma skin cancer
Leah C. Young, Jennifer Listgarten, Martin J. Trotter, Susan E. Andrew, Victor A. Tron
British Journal of Dermatology, 2008 158(1):59-69.
(abstract)
Determining the number of non-spurious arcs in a learned DAG model: Investigation of a
Bayesian and a frequentist approach.
Jennifer Listgarten and David Heckerman
Proceedings of Twenty-Third Conference on Uncertainty in Artificial
Intelligence, UAI Press, July 2007
(
paper)
Analysis of sibling time series data: alignment and difference
detection
Jennifer Listgarten,
Ph.D. Thesis, Department of Computer Science, University of Toronto 2007.
(abstract,
thesis and code)
Bayesian detection of infrequent differences in
sets of time series with shared structure.
Jennifer Listgarten, Radford M. Neal, Sam T. Roweis, Rachel Puckrin and Sean Cutler,
Advances in Neural Information Processing Systems 19, MIT Press,
Cambridge, MA, 2007 (
NIPS 2006).
Best Student Paper, Honorable Mention.
(abstract, paper)
Difference detection in LC-MS data for protein biomarker discovery.
Jennifer Listgarten, Radford M. Neal, Sam T. Roweis, Peter Wong and Andrew Emili,
Bioinformatics, 2007 23:e198-e204 (by way of
ECCB 2006)
Best Student Paper, 3rd prize
(abstract, paper and data set)
Leveraging information across HLA alleles/supertypes improves epitope prediction.
David Heckerman, Carl Kadie, Jennifer Listgarten,
Journal of Computational Biology, 2007 14: 736-746
(shorter version also appears
Proceedings of Research in Computational Molecular Biology. Lecture
Notes in Computer Science, Volume 3909, Mar 2006, 296-308.)
(abstract,
paper)
Web tool, executable and source code available
here, under "Epitope Prediction"
Practical proteomic biomarker discovery: taking a step back to leap
forward.
Jennifer Listgarten and Andrew Emili,
Drug Discovery Today, 2005 10:1697-1702.
(abstract)
(paper)
Statistical and computational methods for comparative proteomic profiling using
liquid chromatography-tandem mass spectrometry.
Jennifer Listgarten and Andrew Emili,
Molecular and Cellular Proteomics, 2005 4:419-434.
(abstract)
(paper)
Multiple alignment of continuous time series.
Jennifer Listgarten, Radford M. Neal, Sam T. Roweis and Andrew Emili,
Advances in Neural Information Processing Systems 17, MIT Press, Cambridge, MA,
2005 (NIPS 2004).
The Continuous Profile Models (CPM) Matlab Toolbox
is available
here.
(abstract, paper, slides, and audio demo)
Predictive models for breast cancer susceptibility from multiple,
single nucleotide polymorphisms.
(abstract)
(paper)
Jennifer Listgarten, S Damaraju,
B Poulin, L Cook, J Dufour, A Driga, J Mackey, D Wishart,
R Greiner and B Zanke,
Clinical Cancer Research 2004:10(8):2725-37.
Clinically validated
benchmarking of normalization techniques for two-colour oligonucleotide
spotted microarray slides.
(abstract)
(paper)
Jennifer Listgarten, K Graham,
S Damaraju, C Cass, J Mackey and B Zanke,
Applied Bioinformatics 2003:2(4)219-228.
Lymphovascular invasion is associated with poor survival in gastric
cancer: an application of gene-expression and tissue array techniques.
BJ Dicken, K Graham, SM Hamilton, S Andrews,
R Lai, Jennifer Listgarten, GS Jhangri, LD Saunders,
S Damaraju and CE Cass,
Annals of Surgery 2006: 243(1):64-73.
Exploring qualitative probabilities for image
understanding
Jennifer Listgarten,
M.Sc. Thesis, Department of Computer Science, University of Toronto, October 2000.
(pdf 1.2MB)
(ps.gz 0.6MB)
