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Article ; Online: To dismantle structural racism in science, scientists need to learn how it works.

Weinreb, Caleb / Sun, Daphne S

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology

2023 Volume 48, Issue 4, Page(s) 579–582

MeSH term(s)	Systemic Racism ; Learning ; Racism
Language	English
Publishing date	2023-01-16
Publishing country	England
Document type	Journal Article ; Review ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	639471-1
ISSN	1740-634X ; 0893-133X
ISSN (online)	1740-634X
ISSN	0893-133X
DOI	10.1038/s41386-023-01534-2
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Lineage reconstruction from clonal correlations.

Weinreb, Caleb / Klein, Allon M

Proceedings of the National Academy of Sciences of the United States of America

2020 Volume 117, Issue 29, Page(s) 17041–17048

Abstract: A central task in developmental biology is to learn the sequence of fate decisions that leads to each mature cell type in a tissue or organism. Recently, clonal labeling of cells using DNA barcodes has emerged as a powerful approach for identifying cells ...

Abstract	A central task in developmental biology is to learn the sequence of fate decisions that leads to each mature cell type in a tissue or organism. Recently, clonal labeling of cells using DNA barcodes has emerged as a powerful approach for identifying cells that share a common ancestry of fate decisions. Here we explore the idea that stochasticity of cell fate choice during tissue development could be harnessed to read out lineage relationships after a single step of clonal barcoding. By considering a generalized multitype branching process, we determine the conditions under which the final distribution of barcodes over observed cell types encodes their bona fide lineage relationships. We then propose a method for inferring the order of fate decisions. Our theory predicts a set of symmetries of barcode covariance that serves as a consistency check for the validity of the method. We show that broken symmetries may be used to detect multiple paths of differentiation to the same cell types. We provide computational tools for general use. When applied to barcoding data in hematopoiesis, these tools reconstruct the classical hematopoietic hierarchy and detect couplings between monocytes and dendritic cells and between erythrocytes and basophils that suggest multiple pathways of differentiation for these lineages.
MeSH term(s)	Animals ; Cell Lineage/genetics ; Cell Lineage/physiology ; DNA Barcoding, Taxonomic/methods ; Decision Trees ; Dendritic Cells/cytology ; Erythrocytes/cytology ; Hematopoiesis/genetics ; Hematopoiesis/physiology ; Leukocytes/cytology ; Models, Biological ; Systems Biology
Language	English
Publishing date	2020-07-06
Publishing country	United States
Document type	Journal Article
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.2000238117
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Article: ArMo: An Articulated Mesh Approach for Mouse 3D Reconstruction.

Bohnslav, James P / Osman, Mohammed Abdal Monium / Jaggi, Akshay / Soares, Sofia / Weinreb, Caleb / Datta, Sandeep Robert / Harvey, Christopher D

bioRxiv : the preprint server for biology

2023

Abstract: Characterizing animal behavior requires methods to distill 3D movements from video data. Though keypoint tracking has emerged as a widely used solution to this problem, it only provides a limited view of pose, reducing the body of an animal to a sparse ... ...

Abstract	Characterizing animal behavior requires methods to distill 3D movements from video data. Though keypoint tracking has emerged as a widely used solution to this problem, it only provides a limited view of pose, reducing the body of an animal to a sparse set of experimenter-defined points. To more completely capture 3D pose, recent studies have fit 3D mesh models to subjects in image and video data. However, despite the importance of mice as a model organism in neuroscience research, these methods have not been applied to the 3D reconstruction of mouse behavior. Here, we present ArMo, an articulated mesh model of the laboratory mouse, and demonstrate its application to multi-camera recordings of head-fixed mice running on a spherical treadmill. Using an end-to-end gradient based optimization procedure, we fit the shape and pose of a dense 3D mouse model to data-derived keypoint and point cloud observations. The resulting reconstructions capture the shape of the animalâ€™s surface while compactly summarizing its movements as a time series of 3D skeletal joint angles. ArMo therefore provides a novel alternative to the sparse representations of pose more commonly used in neuroscience research.
Language	English
Publishing date	2023-02-18
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.02.17.526719
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Article ; Online: Lineage tracing on transcriptional landscapes links state to fate during differentiation.

Weinreb, Caleb / Rodriguez-Fraticelli, Alejo / Camargo, Fernando D / Klein, Allon M

Science (New York, N.Y.)

2020 Volume 367, Issue 6479

Abstract: A challenge in biology is to associate molecular differences among progenitor cells with their capacity to generate mature cell types. Here, we used expressed DNA barcodes to clonally trace transcriptomes over time and applied this to study fate ... ...

Abstract	A challenge in biology is to associate molecular differences among progenitor cells with their capacity to generate mature cell types. Here, we used expressed DNA barcodes to clonally trace transcriptomes over time and applied this to study fate determination in hematopoiesis. We identified states of primed fate potential and located them on a continuous transcriptional landscape. We identified two routes of monocyte differentiation that leave an imprint on mature cells. Analysis of sister cells also revealed cells to have intrinsic fate biases not detectable by single-cell RNA sequencing. Finally, we benchmarked computational methods of dynamic inference from single-cell snapshots, showing that fate choice occurs earlier than is detected by state-of the-art algorithms and that cells progress steadily through pseudotime with precise and consistent dynamics.
MeSH term(s)	Algorithms ; Animals ; Cell Lineage/genetics ; DNA Barcoding, Taxonomic ; Gene Expression ; Hematopoiesis/genetics ; Mice ; Monocytes/cytology ; RNA-Seq ; Single-Cell Analysis/methods ; Transcriptome
Language	English
Publishing date	2020-01-23
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	128410-1
ISSN	1095-9203 ; 0036-8075
ISSN (online)	1095-9203
ISSN	0036-8075
DOI	10.1126/science.aaw3381
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Zs.A 27: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Spontaneous behaviour is structured by reinforcement without explicit reward.

Markowitz, Jeffrey E / Gillis, Winthrop F / Jay, Maya / Wood, Jeffrey / Harris, Ryley W / Cieszkowski, Robert / Scott, Rebecca / Brann, David / Koveal, Dorothy / Kula, Tomasz / Weinreb, Caleb / Osman, Mohammed Abdal Monium / Pinto, Sandra Romero / Uchida, Naoshige / Linderman, Scott W / Sabatini, Bernardo L / Datta, Sandeep Robert

Nature

2023 Volume 614, Issue 7946, Page(s) 108–117

Abstract: Spontaneous animal behaviour is built from action modules that are concatenated by the brain into ... ...

Abstract	Spontaneous animal behaviour is built from action modules that are concatenated by the brain into sequences
MeSH term(s)	Animals ; Mice ; Corpus Striatum/metabolism ; Dopamine/metabolism ; Reinforcement, Psychology ; Reward ; Behavior, Animal ; Cues ; Optogenetics ; Photometry
Chemical Substances	Dopamine (VTD58H1Z2X)
Language	English
Publishing date	2023-01-18
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	120714-3
ISSN	1476-4687 ; 0028-0836
ISSN (online)	1476-4687
ISSN	0028-0836
DOI	10.1038/s41586-022-05611-2
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Zs.A 26: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article: Identification of hierarchical chromatin domains

Weinreb, Caleb / Raphael, Benjamin J

Bioinformatics. 2016 June 01, v. 32, no. 11

2016

Abstract: Motivation: The three-dimensional structure of the genome is an important regulator of many cellular processes including differentiation and gene regulation. Recently, technologies such as Hi-C that combine proximity ligation with high-throughput ... ...

Abstract	Motivation: The three-dimensional structure of the genome is an important regulator of many cellular processes including differentiation and gene regulation. Recently, technologies such as Hi-C that combine proximity ligation with high-throughput sequencing have revealed domains of self-interacting chromatin, called topologically associating domains (TADs), in many organisms. Current methods for identifying TADs using Hi-C data assume that TADs are non-overlapping, despite evidence for a nested structure in which TADs and sub-TADs form a complex hierarchy. Results: We introduce a model for decomposition of contact frequencies into a hierarchy of nested TADs. This model is based on empirical distributions of contact frequencies within TADs, where positions that are far apart have a greater enrichment of contacts than positions that are close together. We find that the increase in contact enrichment with distance is stronger for the inner TAD than for the outer TAD in a TAD/sub-TAD pair. Using this model, we develop the TADtree algorithm for detecting hierarchies of nested TADs. TADtree compares favorably with previous methods, finding TADs with a greater enrichment of chromatin marks such as CTCF at their boundaries. Availability and implementation: A python implementation of TADtree is available at http://compbio.cs.brown.edu/software/ Contact: braphael@cs.brown.edu Supplementary information: Supplementary data are available at Bioinformatics online.
Keywords	algorithms ; bioinformatics ; chromatin ; genes ; high-throughput nucleotide sequencing ; models
Language	English
Dates of publication	2016-0601
Size	p. 1601-1609.
Publishing place	Oxford University Press
Document type	Article
ZDB-ID	1468345-3
ISSN	1460-2059 ; 1367-4811 ; 1367-4803
ISSN (online)	1460-2059 ; 1367-4811
ISSN	1367-4803
DOI	10.1093/bioinformatics/btv485
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Identification of hierarchical chromatin domains.

Weinreb, Caleb / Raphael, Benjamin J

Bioinformatics (Oxford, England)

2015 Volume 32, Issue 11, Page(s) 1601–1609

Abstract	Motivation: The three-dimensional structure of the genome is an important regulator of many cellular processes including differentiation and gene regulation. Recently, technologies such as Hi-C that combine proximity ligation with high-throughput sequencing have revealed domains of self-interacting chromatin, called topologically associating domains (TADs), in many organisms. Current methods for identifying TADs using Hi-C data assume that TADs are non-overlapping, despite evidence for a nested structure in which TADs and sub-TADs form a complex hierarchy. Results: We introduce a model for decomposition of contact frequencies into a hierarchy of nested TADs. This model is based on empirical distributions of contact frequencies within TADs, where positions that are far apart have a greater enrichment of contacts than positions that are close together. We find that the increase in contact enrichment with distance is stronger for the inner TAD than for the outer TAD in a TAD/sub-TAD pair. Using this model, we develop the TADtree algorithm for detecting hierarchies of nested TADs. TADtree compares favorably with previous methods, finding TADs with a greater enrichment of chromatin marks such as CTCF at their boundaries. Availability and implementation: A python implementation of TADtree is available at http://compbio.cs.brown.edu/software/ Contact: braphael@cs.brown.edu Supplementary information: Supplementary data are available at Bioinformatics online.
MeSH term(s)	Cell Differentiation ; Chromatin ; Gene Expression Regulation ; Genome
Chemical Substances	Chromatin
Language	English
Publishing date	2015-08-26
Publishing country	England
Document type	Journal Article
ZDB-ID	1422668-6
ISSN	1367-4811 ; 1367-4803
ISSN (online)	1367-4811
ISSN	1367-4803
DOI	10.1093/bioinformatics/btv485
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Article ; Online: Lifelong multilineage contribution by embryonic-born blood progenitors.

Patel, Sachin H / Christodoulou, Constantina / Weinreb, Caleb / Yu, Qi / da Rocha, Edroaldo Lummertz / Pepe-Mooney, Brian J / Bowling, Sarah / Li, Li / Osorio, Fernando G / Daley, George Q / Camargo, Fernando D

Nature

2022 Volume 606, Issue 7915, Page(s) 747–753

Abstract: Haematopoietic stem cells (HSCs) arise in the embryo from the arterial endothelium through a process known as the endothelial-to-haematopoietic transition (EHT) ...

Abstract	Haematopoietic stem cells (HSCs) arise in the embryo from the arterial endothelium through a process known as the endothelial-to-haematopoietic transition (EHT)
MeSH term(s)	Aging ; Animals ; Cell Lineage ; Embryo, Mammalian/cytology ; Hematopoiesis ; Hematopoietic Stem Cells/cytology ; Mice ; Multipotent Stem Cells/cytology
Language	English
Publishing date	2022-06-15
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/s41586-022-04804-z
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Article ; Online: SPRING: a kinetic interface for visualizing high dimensional single-cell expression data.

Weinreb, Caleb / Wolock, Samuel / Klein, Allon M

Bioinformatics (Oxford, England)

2017 Volume 34, Issue 7, Page(s) 1246–1248

Abstract: Motivation: Single-cell gene expression profiling technologies can map the cell states in a tissue or organism. As these technologies become more common, there is a need for computational tools to explore the data they produce. In particular, ... ...

Abstract	Motivation: Single-cell gene expression profiling technologies can map the cell states in a tissue or organism. As these technologies become more common, there is a need for computational tools to explore the data they produce. In particular, visualizing continuous gene expression topologies can be improved, since current tools tend to fragment gene expression continua or capture only limited features of complex population topologies. Results: Force-directed layouts of k-nearest-neighbor graphs can visualize continuous gene expression topologies in a manner that preserves high-dimensional relationships and captures complex population topologies. We describe SPRING, a pipeline for data filtering, normalization and visualization using force-directed layouts and show that it reveals more detailed biological relationships than existing approaches when applied to branching gene expression trajectories from hematopoietic progenitor cells and cells of the upper airway epithelium. Visualizations from SPRING are also more reproducible than those of stochastic visualization methods such as tSNE, a state-of-the-art tool. We provide SPRING as an interactive web-tool with an easy to use GUI. Availability and implementation: https://kleintools.hms.harvard.edu/tools/spring.html, https://github.com/AllonKleinLab/SPRING/. Contact: calebsw@gmail.com or allon_klein@hms.harvard.edu. Supplementary information: Supplementary data are available at Bioinformatics online.
MeSH term(s)	Cluster Analysis ; Computational Biology/methods ; Gene Expression Profiling/methods ; Hematopoietic Stem Cells/metabolism ; Humans ; Respiratory Mucosa/metabolism ; Sequence Analysis, RNA/methods ; Single-Cell Analysis/methods ; Software
Language	English
Publishing date	2017-12-26
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1422668-6
ISSN	1367-4811 ; 1367-4803
ISSN (online)	1367-4811
ISSN	1367-4803
DOI	10.1093/bioinformatics/btx792
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Article ; Online: Non-neural expression of SARS-CoV-2 entry genes in the olfactory epithelium suggests mechanisms underlying anosmia in COVID-19 patients

David Brann / Tatsuya Tsukahara / Caleb Weinreb / Darren W. Logan / Sandeep Robert Datta

Abstract: Recent reports suggest an association between COVID-19 and altered olfactory function. Here we analyze bulk and single cell RNA-Seq datasets to identify cell types in the olfactory epithelium that express molecules that mediate infection by SARS-CoV-2 ( ... ...

Abstract	Recent reports suggest an association between COVID-19 and altered olfactory function. Here we analyze bulk and single cell RNA-Seq datasets to identify cell types in the olfactory epithelium that express molecules that mediate infection by SARS-CoV-2 (CoV-2), the causal agent in COVID-19. We find in both mouse and human datasets that olfactory sensory neurons do not express two key genes involved in CoV-2 entry, ACE2 and TMPRSS2. In contrast, olfactory epithelial support cells and stem cells express both of these genes, as do cells in the nasal respiratory epithelium. Taken together, these findings suggest possible mechanisms through which CoV-2 infection could lead to anosmia or other forms of olfactory dysfunction.
Keywords	covid19
Publisher	biorxiv
Document type	Article ; Online
DOI	10.1101/2020.03.25.009084
Database	COVID19

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