Nir Yosef
University of California, Berkeley
CellGeneticsBioinformaticsBiologyCell biology
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Publications 124
#1Adam Gayoso (University of California, Berkeley)
#2Zoë Steier (University of California, Berkeley)H-Index: 1
Last. Nir Yosef (University of California, Berkeley)H-Index: 33
view all 7 authors...
The paired measurement of RNA and surface protein abundance in single cells with CITE-seq is a promising approach to connect transcriptional variation with cell phenotypes and functions. However, each data modality exhibits unique technical biases, making it challenging to conduct a joint analysis and combine these two views into a unified representation of cell state. Here we present Total Variational Inference (totalVI), a framework for the joint probabilistic analysis of paired RNA and protei...
#1Jeffrey J. Quinn (UCSF: University of California, San Francisco)H-Index: 8
#2Matthew G. Jones (UCSF: University of California, San Francisco)H-Index: 1
Last. Jonathan S. Weissman (UCSF: University of California, San Francisco)H-Index: 110
view all 6 authors...
Consequential events in cancer progression are typically rare and occur in the unobserved past. Detailed cell phylogenies can capture the history and chronology of such transient events - including metastasis. Here, we applied our Cas9-based lineage tracer to study metastatic progression in a lung cancer xenograft mouse model, revealing the underlying rates, routes, and patterns of metastasis. We report deeply resolved phylogenies for tens of thousands of metastatically disseminated cancer cells...
#1Saige L. Pompura (Yale University)H-Index: 1
#2Allon Wagner (University of California, Berkeley)H-Index: 11
Last. David A. Hafler (Yale University)H-Index: 114
view all 7 authors...
FoxP3 positive regulatory T cells (Tregs) rely on fatty acid oxidation (FAO)-driven OXPHOS for differentiation and function. Recent data have demonstrated a role for Tregs in the maintenance of tissue homeostasis with tissue-resident Tregs possessing tissue-specific transcriptomes. However, specific signals that establish these tissue-resident Tregs programs are largely unknown. As Tregs metabolically rely on FAO, and considering the lipid-rich environments of tissues, we hypothesized that envir...
#1Matthew G. JonesH-Index: 1
#2Alex Khodaverdian (University of California, Berkeley)H-Index: 1
Last. Nir YosefH-Index: 33
view all 9 authors...
The pairing of CRISPR/Cas9-based gene editing with massively parallel single-cell readouts now enables large-scale lineage tracing. However, the rapid growth in complexity of data from these assays has outpaced our ability to accurately infer phylogenetic relationships. First, we introduce Cassiopeia-a suite of scalable maximum parsimony approaches for tree reconstruction. Second, we provide a simulation framework for evaluating algorithms and exploring lineage tracer design principles. Finally,...
1 CitationsSource
#1Allon Wagner (University of California, Berkeley)H-Index: 11
#2Chao Wang (Brigham and Women's Hospital)H-Index: 14
Last. Vivian Paraskevi Douglas (MEE: Massachusetts Eye and Ear Infirmary)
view all 17 authors...
Cellular metabolism, a key regulator of immune responses, is difficult to study with current technologies in individual cells Here, we present Compass, an algorithm to characterize the metabolic state of cells based on single-cell RNA-Seq and flux balance analysis. We applied Compass to associate metabolic states with functional variability (pathogenic potential) amongst Th17 cells and recovered a metabolic switch between glycolysis and fatty acid oxidation, akin to known differences between Th1...
#1Valentine Svensson (California Institute of Technology)H-Index: 12
#2Adam Gayoso (University of California, Berkeley)
Last. Lior Pachter (California Institute of Technology)H-Index: 55
view all 4 authors...
MOTIVATION: Single-cell RNA-seq makes possible the investigation of variability in gene expression among cells, and dependence of variation on cell type. Statistical inference methods for such analyses must be scalable, and ideally interpretable. RESULTS: We present an approach based on a modification of a recently published highly scalable variational autoencoder framework that provides interpretability without sacrificing much accuracy. We demonstrate that our approach enables identification o...
3 CitationsSource
#1Romain Lopez (University of California, Berkeley)H-Index: 5
#2Pierre BoyeauH-Index: 1
Last. Jeffrey RegierH-Index: 5
view all 5 authors...
To make decisions based on a model fit by Auto-Encoding Variational Bayes (AEVB), practitioners typically use importance sampling to estimate a functional of the posterior distribution. The variational distribution found by AEVB serves as the proposal distribution for importance sampling. However, this proposal distribution may give unreliable (high variance) importance sampling estimates, thus leading to poor decisions. We explore how changing the objective function for learning the variational...
#1David DeTomaso (University of California, Berkeley)H-Index: 4
#2Nir Yosef (University of California, Berkeley)H-Index: 33
Two fundamental aims that emerge when analyzing single-cell RNA-seq data are that of identifying which genes vary in an informative manner and determining how these genes organize into modules. Here we propose a general approach to these problems that operates directly on a given metric of cell-cell similarity, allowing for its integration with any method (linear or non linear) for identifying the primary axes of transcriptional variation between cells. Additionally, we show that when using mult...
2 CitationsSource
#1Daniel J. Puleston (University of Oxford)H-Index: 11
#1Daniel Puleston (MPG: Max Planck Society)
Last. Cameron S. Field (MPG: Max Planck Society)H-Index: 2
view all 23 authors...
We report here a central role for polyamines in T cell differentiation and function. Deficiency in ornithine decarboxylase (ODC), a critical enzyme for polyamine synthesis, resulted in a profound failure of CD4+ T cells to adopt correct subset specification, underscored by ectopic expression of multiple cytokines and lineage-defining transcription factors across TH1, TH2, TH17, and Treg polarizing conditions, and enhanced colitogenic potential. T cells deficient in deoxyhypusine synthase (DHPS) ...
#1Chao Wang (Brigham and Women's Hospital)H-Index: 14
#2Allon Wagner (University of California, Berkeley)H-Index: 11
Last. Alexandra Schnell (Brigham and Women's Hospital)H-Index: 2
view all 21 authors...
Cellular metabolism can orchestrate immune cell function. We previously demonstrated that lipid biosynthesis represents one such gatekeeper to Th17 cell functional state. Utilizing Compass, a transcriptome-based algorithm for prediction of metabolic flux, we constructed a comprehensive metabolic circuitry for Th17 cell function and identified the polyamine pathway as a candidate metabolic node, the flux of which regulates the inflammatory function of T cells. Testing this prediction, we found th...