Gottardo lab

The Gottardo Group develops and applies advanced statistical and computational methods to address key biological questions in oncology. Our research focuses on the generation and analysis of high‑dimensional data from cutting‑edge technologies, including single‑cell and spatial transcriptomics and proteomics, and their integration with clinical datasets. By adopting an end‑to‑end strategy—from experimental design and data generation to biological and clinical interpretation—we ensure that our methods are closely aligned with biological challenges and designed for strong translational impact. Our work spans a broad range of applications in cancer research, including the characterization of immune responses to cancer and the study of patient responses to immunotherapies. By harnessing cutting‑edge data science, we aim to advance the understanding of immune mechanisms in oncology and support the development of more effective therapeutic strategies. ...

Research projects

Single-cell and spatial transcriptomics

Our group develops statistical methods and tools- particularly probabilistic and Bayesian approaches- for novel single and spatial technologies.

One of our major accomplishments in this field is our contribution to MOSAIC (Multi-Omics Spatial Atlas in Cancer) - a multi‑center clinical project aimed at comprehensively characterizing thousands of tumor samples with spatial and single‑cell technologies across diverse cancer types. Whitin this international initiative, we contributed our expertise in advanced data science to help build the world’s largest spatially-resolved omics reference database in oncology (MOSAIC: Intra-tumoral heterogeneity characterization through large-scale spatial and cell-resolved multi-omics profiling | bioRxiv; Dong et al, 2025).

In recent years, one of our most significant achievements has been the development of the first statistical model to account for the bimodal gene expression patterns commonly observed in single‑cell data. This model is implemented in the MAST package, which has since become one of the most widely cited methods for differential gene expression analysis in scRNA‑seq studies.

We also introduced one of the first models for the analysis of spatial transcriptomics that enables near single-cell resolution analysis of 10X Visium data. This method is implemented in the open-source BayesSpace package. Both MAST and BayesSpace are available from the Bioconductor project. More recently, we have developed additional methodologies for spatial transcriptomics, including tools for preprocessing, segmentation, machine learning, and AI-based analysis. We have also made key contributions to the Bioconductor ecosystem through the OSTA book (https://bioconductor.org/books/release/OSTA/).

Characterizing responses to immunotherapy

Using single‑cell and spatial computational analyses, our group contributes to numerous studies aimed at characterizing the tumor microenvironment (TME) —including immune cells—to better understand mechanisms of response and relapse to immunotherapy.

One example is our participation in IMMUcan (Integrated iMMUnoprofiling of large adaptive CANcer patient cohorts), a European consortium focused on leveraging multi‑omics data to uncover how the TME drives cancer progression. To support this effort, we provide our expertise in data integration and pan‑cancer analyses to identify shared spatial patterns of the TME across cancer types. We also apply emerging spatial omics methods to the consortium’s spatial proteomics data and collaborate closely with other groups to integrate multi‑omics data across different cancers.

In previous years, we have developed and applied computational tools to identify novel biomarkers of responses to anti-PD1 therapy (Greene et al 2021) and escape mechanisms to adoptive T-cell therapies (Paulson et al 2018, Chapuis et al 2019, Lahman et al. 2022).

Team

Other members

Selected Publications

The ubiquitin ligase KLHL6 drives resistance to CD8(+) T cell dysfunction.

Cheng H, Su Y, Pan X, (...), Gottardo R, Greenberg PD, Li G

Nature – 2026 Jan 14

Orchestrating Spatial Transcriptomics Analysis with Bioconductor.

Crowell HL, Dong Y, Billato I, (...), Robinson MD, Hicks SC, Weber LM

bioRxiv : the preprint server for biology – 2025 Nov 21

ADTnorm: robust integration of single-cell protein measurement across CITE-seq datasets.

Zheng Y, Caron DP, Kim JY, (...), Stuart KD, Sims PA, Gottardo R

Nature communications – 2025 Jul 1

Transcriptome analysis of archived tumors by Visium, GeoMx DSP, and Chromium reveals patient heterogeneity.

Dong Y, Saglietti C, Bayard Q, (...), Gottardo R, Homicsko K, Madissoon E

Nature communications – 2025 May 12

Immune modules to guide diagnosis and personalized treatment of inflammatory skin diseases.

Seremet T, Di Domizio J, Girardin A, (...), Gottardo R, Conrad C, Gilliet M

Nature communications – 2024 Dec 18

RAIN: machine learning-based identification for HIV-1 bNAbs.

Foglierini M, Nortier P, Schelling R, (...), Doria-Rose NA, Gottardo R, Perez L

Nature communications – 2024 Jun 24

The tidyomics ecosystem: Enhancing omic data analyses.

Hutchison WJ, Keyes TJ, tidyomics Consortium, (...), Papenfuss AT, Love MI, Mangiola S

bioRxiv : the preprint server for biology – 2024 May 22

Differentiation of IL-26(+) T(H)17 intermediates into IL-17A producers via epithelial crosstalk in psoriasis.

Fries A, Saidoune F, Kuonen F, (...), Modlin RL, Di Domizio J, Gilliet M

Nature communications – 2023 Jun 30

An information theoretic approach to detecting spatially varying genes.

Jones DC, Danaher P, Kim Y, (...), Beechem JM, Gottardo R, Newell EW

Cell reports methods – 2023 Jun 16

Extricating human tumour immune alterations from tissue inflammation.

Mair F, Erickson JR, Frutoso M, (...), Barber B, Gottardo R, Prlic M

Nature – 2022 May 11

Neoantigen-specific CD4(+) T cells in human melanoma have diverse differentiation states and correlate with CD8(+) T cell, macrophage, and B cell function.

Veatch JR, Lee SM, Shasha C, (...), Newell E, Gottardo R, Riddell SR

Cancer cell – 2022 Apr 11

Multiple early factors anticipate post-acute COVID-19 sequelae.

Su Y, Yuan D, Chen DG, (...), Davis MM, Goldman JD, Heath JR

Cell – 2022 Jan 25

Transcriptional correlates of malaria in RTS,S/AS01-vaccinated African children: a matched case-control study.

Moncunill G, Carnes J, Chad Young W, (...), Dobaño C, Stuart K, Gottardo R

eLife – 2022 Jan 21

Spatial transcriptomics at subspot resolution with BayesSpace.

Zhao E, Stone MR, Ren X, (...), Nghiem P, Bielas JH, Gottardo R

Nature biotechnology – 2021 Jun 3

Integrated analysis of multimodal single-cell data.

Hao Y, Hao S, Andersen-Nissen E, (...), Gottardo R, Smibert P, Satija R

Cell – 2021 May 31

Immunogenic Chemotherapy Enhances Recruitment of CAR-T Cells to Lung Tumors and Improves Antitumor Efficacy when Combined with Checkpoint Blockade.

Srivastava S, Furlan SN, Jaeger-Ruckstuhl CA, (...), Gottardo R, Maloney DG, Riddell SR

Cancer cell – 2020 Dec 24

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2nd Symposium on AI for Clinical and Translational Medicine | May 6th

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AGORA PRS Seminar | November 4th

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AGORA PRS Seminar | October 7th

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🌱 Second AGORA Sustainability Day | May 21st

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INVITED TALK, Prof. Valentina Boeva | January 16th

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AGORA PRS Seminar | December 10th

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AI Driven-Advances in Clinical and Translational Medicine | November 13th

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Invited Talk, Dr. Guillaume Jaume | May 27th

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AGORA PRS | May 21st

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AGORA PRS | April 25th

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AGORA PRS | April 4th

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AGORA PRS | March 28th