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Article ; Online: Genomic Analysis of Foxp3 Function in Regulatory T Cells.

Dolsten, Gabriel A / Pritykin, Yuri

Journal of immunology (Baltimore, Md. : 1950)

2023 Volume 210, Issue 7, Page(s) 880–887

Abstract: Regulatory T (Treg) cells are critical for tolerance to self-antigens and for preventing autoimmunity. Foxp3 has been identified as a Treg cell lineage-defining transcription factor controlling Treg cell differentiation and function. In this article, we ... ...

Abstract	Regulatory T (Treg) cells are critical for tolerance to self-antigens and for preventing autoimmunity. Foxp3 has been identified as a Treg cell lineage-defining transcription factor controlling Treg cell differentiation and function. In this article, we review the current mechanistic and systemic understanding of Foxp3 function enabled by experimental and computational advances in high-throughput genomics.
MeSH term(s)	T-Lymphocytes, Regulatory ; Cell Differentiation/genetics ; Gene Expression Regulation ; Transcription Factors/genetics ; Genomics ; Forkhead Transcription Factors/metabolism
Chemical Substances	Transcription Factors ; Forkhead Transcription Factors
Language	English
Publishing date	2023-03-22
Publishing country	United States
Document type	Review ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	3056-9
ISSN	1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
ISSN (online)	1550-6606
ISSN	0022-1767 ; 1048-3233 ; 1047-7381
DOI	10.4049/jimmunol.2200864
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Article ; Online: Single-cell multi-ome regression models identify functional and disease-associated enhancers and enable chromatin potential analysis.

Mitra, Sneha / Malik, Rohan / Wong, Wilfred / Rahman, Afsana / Hartemink, Alexander J / Pritykin, Yuri / Dey, Kushal K / Leslie, Christina S

Nature genetics

2024 Volume 56, Issue 4, Page(s) 627–636

Abstract: We present a gene-level regulatory model, single-cell ATAC + RNA linking (SCARlink), which predicts single-cell gene expression and links enhancers to target genes using multi-ome (scRNA-seq and scATAC-seq co-assay) sequencing data. The approach uses ... ...

Abstract	We present a gene-level regulatory model, single-cell ATAC + RNA linking (SCARlink), which predicts single-cell gene expression and links enhancers to target genes using multi-ome (scRNA-seq and scATAC-seq co-assay) sequencing data. The approach uses regularized Poisson regression on tile-level accessibility data to jointly model all regulatory effects at a gene locus, avoiding the limitations of pairwise gene-peak correlations and dependence on peak calling. SCARlink outperformed existing gene scoring methods for imputing gene expression from chromatin accessibility across high-coverage multi-ome datasets while giving comparable to improved performance on low-coverage datasets. Shapley value analysis on trained models identified cell-type-specific gene enhancers that are validated by promoter capture Hi-C and are 11× to 15× and 5× to 12× enriched in fine-mapped eQTLs and fine-mapped genome-wide association study (GWAS) variants, respectively. We further show that SCARlink-predicted and observed gene expression vectors provide a robust way to compute a chromatin potential vector field to enable developmental trajectory analysis.
MeSH term(s)	Chromatin/genetics ; Genome-Wide Association Study ; Regulatory Sequences, Nucleic Acid ; Gene Expression Regulation ; Promoter Regions, Genetic/genetics ; RNA ; Single-Cell Analysis/methods
Chemical Substances	Chromatin ; RNA (63231-63-0)
Language	English
Publishing date	2024-03-21
Publishing country	United States
Document type	Journal Article
ZDB-ID	1108734-1
ISSN	1546-1718 ; 1061-4036
ISSN (online)	1546-1718
ISSN	1061-4036
DOI	10.1038/s41588-024-01689-8
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Zs.A 3613: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article: Universal recording of cell-cell contacts

Nakandakari-Higa, Sandra / Canesso, Maria C C / Walker, Sarah / Chudnovskiy, Aleksey / Jacobsen, Johanne T / Bilanovic, Jana / Parigi, S Martina / Fiedorczuk, Karol / Fuchs, Elaine / Bilate, Angelina M / Pasqual, Giulia / Mucida, Daniel / Pritykin, Yuri / Victora, Gabriel D

bioRxiv : the preprint server for biology

2023

Abstract: Cellular interactions are essential for tissue organization and functionality. In particular, immune cells rely on direct and usually transient interactions with other immune and non-immune populations to specify and regulate their function. To study ... ...

Abstract	Cellular interactions are essential for tissue organization and functionality. In particular, immune cells rely on direct and usually transient interactions with other immune and non-immune populations to specify and regulate their function. To study these "kiss-and-run" interactions directly
Language	English
Publishing date	2023-04-18
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.03.16.533003
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Article ; Online: Simple topological features reflect dynamics and modularity in protein interaction networks.

Pritykin, Yuri / Singh, Mona

PLoS computational biology

2013 Volume 9, Issue 10, Page(s) e1003243

Abstract: The availability of large-scale protein-protein interaction networks for numerous organisms provides an opportunity to comprehensively analyze whether simple properties of proteins are predictive of the roles they play in the functional organization of ... ...

Abstract	The availability of large-scale protein-protein interaction networks for numerous organisms provides an opportunity to comprehensively analyze whether simple properties of proteins are predictive of the roles they play in the functional organization of the cell. We begin by re-examining an influential but controversial characterization of the dynamic modularity of the S. cerevisiae interactome that incorporated gene expression data into network analysis. We analyse the protein-protein interaction networks of five organisms, S. cerevisiae, H. sapiens, D. melanogaster, A. thaliana, and E. coli, and confirm significant and consistent functional and structural differences between hub proteins that are co-expressed with their interacting partners and those that are not, and support the view that the former tend to be intramodular whereas the latter tend to be intermodular. However, we also demonstrate that in each of these organisms, simple topological measures are significantly correlated with the average co-expression of a hub with its partners, independent of any classification, and therefore also reflect protein intra- and inter- modularity. Further, cross-interactomic analysis demonstrates that these simple topological characteristics of hub proteins tend to be conserved across organisms. Overall, we give evidence that purely topological features of static interaction networks reflect aspects of the dynamics and modularity of interactomes as well as previous measures incorporating expression data, and are a powerful means for understanding the dynamic roles of hubs in interactomes.
MeSH term(s)	Animals ; Cluster Analysis ; Computational Biology/methods ; Databases, Protein ; Drosophila melanogaster ; Escherichia coli ; Humans ; Protein Interaction Mapping/methods ; Protein Interaction Maps/physiology ; Proteins/chemistry ; Proteins/metabolism ; Saccharomyces cerevisiae ; Statistics, Nonparametric
Chemical Substances	Proteins
Language	English
Publishing date	2013-10-10
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2193340-6
ISSN	1553-7358 ; 1553-734X
ISSN (online)	1553-7358
ISSN	1553-734X
DOI	10.1371/journal.pcbi.1003243
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Article ; Online: Hierarchical regulation of the resting and activated T cell epigenome by major transcription factor families.

Zhong, Yi / Walker, Sarah K / Pritykin, Yuri / Leslie, Christina S / Rudensky, Alexander Y / van der Veeken, Joris

Nature immunology

2021 Volume 23, Issue 1, Page(s) 122–134

Abstract: T cell activation, a key early event in the adaptive immune response, is subject to elaborate transcriptional control. In the present study, we examined how the activities of eight major transcription factor (TF) families are integrated to shape the ... ...

Abstract	T cell activation, a key early event in the adaptive immune response, is subject to elaborate transcriptional control. In the present study, we examined how the activities of eight major transcription factor (TF) families are integrated to shape the epigenome of naive and activated CD4 and CD8 T cells. By leveraging extensive polymorphisms in evolutionarily divergent mice, we identified the 'heavy lifters' positively influencing chromatin accessibility. Members of Ets, Runx and TCF/Lef TF families occupied the vast majority of accessible chromatin regions, acting as 'housekeepers', 'universal amplifiers' and 'placeholders', respectively, at sites that maintained or gained accessibility upon T cell activation. In addition, a small subset of strongly induced immune response genes displayed a noncanonical TF recruitment pattern. Our study provides a key resource and foundation for the understanding of transcriptional and epigenetic regulation in T cells and offers a new perspective on the hierarchical interactions between critical TFs.
MeSH term(s)	Adaptive Immunity/immunology ; Animals ; CD4-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/immunology ; Chromatin/immunology ; Epigenesis, Genetic/immunology ; Epigenome/immunology ; Gene Expression Regulation/immunology ; Lymphocyte Activation/immunology ; Male ; Mice ; Transcription Factors/immunology
Chemical Substances	Chromatin ; Transcription Factors
Language	English
Publishing date	2021-12-22
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2016987-5
ISSN	1529-2916 ; 1529-2908
ISSN (online)	1529-2916
ISSN	1529-2908
DOI	10.1038/s41590-021-01086-x
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Zs.A 5294: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article: A unified atlas of CD8 T cell dysfunctional states in cancer and infection

Pritykin, Yuri / van der Veeken, Joris / Pine, Allison R / Zhong, Yi / Sahin, Merve / Mazutis, Linas / Pe’er, Dana / Rudensky, Alexander Y / Leslie, Christina S

Molecular cell. 2021 June 03, v. 81, no. 11

2021

Abstract: CD8 T cells play an essential role in defense against viral and bacterial infections and in tumor immunity. Deciphering T cell loss of functionality is complicated by the conspicuous heterogeneity of CD8 T cell states described across experimental and ... ...

Abstract	CD8 T cells play an essential role in defense against viral and bacterial infections and in tumor immunity. Deciphering T cell loss of functionality is complicated by the conspicuous heterogeneity of CD8 T cell states described across experimental and clinical settings. By carrying out a unified analysis of over 300 assay for transposase-accessible chromatin sequencing (ATAC-seq) and RNA sequencing (RNA-seq) experiments from 12 studies of CD8 T cells in cancer and infection, we defined a shared differentiation trajectory toward dysfunction and its underlying transcriptional drivers and revealed a universal early bifurcation of functional and dysfunctional T cell states across models. Experimental dissection of acute and chronic viral infection using single-cell ATAC (scATAC)-seq and allele-specific single-cell RNA (scRNA)-seq identified state-specific drivers and captured the emergence of similar TCF1⁺ progenitor-like populations at an early branch point, at which functional and dysfunctional T cells diverge. Our atlas of CD8 T cell states will facilitate mechanistic studies of T cell immunity and translational efforts.
Keywords	CD8-positive T-lymphocytes ; RNA ; chromatin ; dissection ; immunity ; neoplasms ; sequence analysis ; transcription (genetics)
Language	English
Dates of publication	2021-0603
Size	p. 2477-2493.e10.
Publishing place	Elsevier Inc.
Document type	Article
Note	NAL-AP-2-clean
ZDB-ID	1415236-8
ISSN	1097-4164 ; 1097-2765
ISSN (online)	1097-4164
ISSN	1097-2765
DOI	10.1016/j.molcel.2021.03.045
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Transcription factor Foxp1 regulates Foxp3 chromatin binding and coordinates regulatory T cell function.

Konopacki, Catherine / Pritykin, Yuri / Rubtsov, Yury / Leslie, Christina S / Rudensky, Alexander Y

Nature immunology

2019 Volume 20, Issue 2, Page(s) 232–242

Abstract: Regulatory T cells ( ... ...

Abstract	Regulatory T cells (T
MeSH term(s)	Animals ; Cells, Cultured ; Chromatin/metabolism ; Female ; Forkhead Transcription Factors/genetics ; Forkhead Transcription Factors/immunology ; Forkhead Transcription Factors/metabolism ; Gene Expression Regulation/immunology ; Interleukin-2/immunology ; Interleukin-2/metabolism ; Male ; Mice ; Mice, Transgenic ; Primary Cell Culture ; Repressor Proteins/genetics ; Repressor Proteins/immunology ; Repressor Proteins/metabolism ; Signal Transduction/genetics ; Signal Transduction/immunology ; T-Lymphocytes, Regulatory/immunology ; T-Lymphocytes, Regulatory/metabolism
Chemical Substances	Chromatin ; Forkhead Transcription Factors ; Foxp1 protein, mouse ; Foxp3 protein, mouse ; Interleukin-2 ; Repressor Proteins
Language	English
Publishing date	2019-01-14
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2016987-5
ISSN	1529-2916 ; 1529-2908
ISSN (online)	1529-2916
ISSN	1529-2908
DOI	10.1038/s41590-018-0291-z
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Article ; Online: Universal recording of immune cell interactions in vivo.

Nakandakari-Higa, Sandra / Walker, Sarah / Canesso, Maria C C / van der Heide, Verena / Chudnovskiy, Aleksey / Kim, Dong-Yoon / Jacobsen, Johanne T / Parsa, Roham / Bilanovic, Jana / Parigi, S Martina / Fiedorczuk, Karol / Fuchs, Elaine / Bilate, Angelina M / Pasqual, Giulia / Mucida, Daniel / Kamphorst, Alice O / Pritykin, Yuri / Victora, Gabriel D

Nature

2024 Volume 627, Issue 8003, Page(s) 399–406

Abstract: Immune cells rely on transient physical interactions with other immune and non-immune populations to regulate their ... ...

Abstract	Immune cells rely on transient physical interactions with other immune and non-immune populations to regulate their function
MeSH term(s)	CD8-Positive T-Lymphocytes/cytology ; CD8-Positive T-Lymphocytes/immunology ; Cell Communication/immunology ; Dendritic Cells/cytology ; Dendritic Cells/immunology ; Ligands ; T-Lymphocytes, Regulatory/cytology ; T-Lymphocytes, Regulatory/immunology ; T Follicular Helper Cells/cytology ; T Follicular Helper Cells/immunology ; B-Lymphocytes/cytology ; B-Lymphocytes/immunology ; Germinal Center/cytology ; Single-Cell Gene Expression Analysis ; Epithelial Cells/cytology ; Epithelial Cells/immunology ; Intestinal Mucosa/cytology ; Intestinal Mucosa/immunology ; Lymphocytic choriomeningitis virus/immunology ; Lymphocytic Choriomeningitis/immunology ; Lymphocytic Choriomeningitis/virology ; Organ Specificity
Chemical Substances	Ligands
Language	English
Publishing date	2024-03-06
Publishing country	England
Document type	Journal Article
ZDB-ID	120714-3
ISSN	1476-4687 ; 0028-0836
ISSN (online)	1476-4687
ISSN	0028-0836
DOI	10.1038/s41586-024-07134-4
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Book ; Online: On Almost Periodicity Criteria for Morphic Sequences in Some Particular Cases

Pritykin, Yuri

2007

Abstract: In some particular cases we give criteria for morphic sequences to be almost periodic (=uniformly recurrent). Namely, we deal with fixed points of non-erasing morphisms and with automatic sequences. In both cases a polynomial-time algorithm solving the ... ...

Abstract	In some particular cases we give criteria for morphic sequences to be almost periodic (=uniformly recurrent). Namely, we deal with fixed points of non-erasing morphisms and with automatic sequences. In both cases a polynomial-time algorithm solving the problem is found. A result more or less supporting the conjecture of decidability of the general problem is given. Comment: 9 pages. To be presented on 11th International Conference on Developments in Language Theory (DLT'2007), Turku, Finland, July 2007.
Keywords	Computer Science - Discrete Mathematics ; Computer Science - Logic in Computer Science ; G.2.1 ; F.2.2 ; F.4.3
Publishing date	2007-04-02
Publishing country	us
Document type	Book ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Integrative analysis unveils new functions for the

Pritykin, Yuri / Brito, Tarcisio / Schupbach, Trudi / Singh, Mona / Pane, Attilio

RNA (New York, N.Y.)

2017 Volume 23, Issue 7, Page(s) 1097–1109

Abstract: Piwi-interacting RNAs (piRNAs) are central components of the piRNA pathway, which directs transposon silencing and guarantees genome integrity in the germ cells of several metazoans. ... ...

Abstract	Piwi-interacting RNAs (piRNAs) are central components of the piRNA pathway, which directs transposon silencing and guarantees genome integrity in the germ cells of several metazoans. In
MeSH term(s)	Animals ; Chromatin Immunoprecipitation ; DNA Transposable Elements ; Drosophila Proteins/genetics ; Drosophila Proteins/metabolism ; Drosophila melanogaster/genetics ; Drosophila melanogaster/metabolism ; Female ; Gene Expression Regulation ; Gene Expression Regulation, Developmental ; Mutation ; Ovary/chemistry ; Ovary/growth & development ; RNA, Small Interfering/metabolism ; RNA, Untranslated/metabolism ; RNA-Binding Proteins/genetics ; RNA-Binding Proteins/metabolism ; Sequence Analysis, RNA/methods
Chemical Substances	Cuff protein, Drosophila ; DNA Transposable Elements ; Drosophila Proteins ; RNA, Small Interfering ; RNA, Untranslated ; RNA-Binding Proteins
Language	English
Publishing date	2017-04-18
Publishing country	United States
Document type	Journal Article
ZDB-ID	1241540-6
ISSN	1469-9001 ; 1355-8382
ISSN (online)	1469-9001
ISSN	1355-8382
DOI	10.1261/rna.058594.116
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