Aaron Rosenfeld

Aaron Rosenfeld
University of Pennsylvania | UP · Department of Pathology and Laboratory Medicine

M.S. Computer Science

About

51
Publications
7,930
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1,886
Citations

Publications

Publications (51)
Article
Full-text available
Datasets from high-throughput sequencing technologies have yielded a vast amount of data about organisms in environmental samples. Yet, it is still a challenge to assess the exact organism content in these samples because the task of taxonomic classification is too computationally complex to annotate all reads in a dataset. An easy-to-use webserver...
Article
Full-text available
B-cell responses result in clonal expansion, and can occur in a variety of tissues. To define how B-cell clones are distributed in the body, we sequenced 933,427 B-cell clonal lineages and mapped them to eight different anatomic compartments in six human organ donors. We show that large B-cell clones partition into two broad networks—one spans the...
Article
Full-text available
B cell clones expand and contract during adaptive immune responses and can persist or grow uncontrollably in lymphoproliferative disorders. One way to monitor and track B cell clones is to perform large-scale sampling of bulk cell populations, amplifying, and sequencing antibody gene rearrangements by next-generation sequencing (NGS). Here, we desc...
Article
Full-text available
ImmuneDB is a system for storing and analyzing high-throughput immune receptor sequencing data. Unlike most existing tools, which utilize flat-files, ImmuneDB stores data in a well-structured MySQL database, enabling efficient data queries. It can take raw sequencing data as input and annotate receptor gene usage, infer clonotypes, aggregate result...
Article
Full-text available
Although critical illness has been associated with SARS-CoV-2-induced hyperinflammation, the immune correlates of severe COVID-19 remain unclear. Here, we comprehensively analyzed peripheral blood immune perturbations in 42 SARS-CoV-2 infected and recovered individuals. We identified extensive induction and activation of multiple immune lineages, i...
Preprint
Full-text available
Germinal centers (GCs), sites of antibody affinity maturation, are organized into dark (DZ) and light (LZ) zones. Here, we uncovered a B cell intrinsic role for STAT3 in GC DZ and LZ organization. Altered zonal organization of STAT3-deficient GCs dampened GC output of long-lived plasma cells (LL-PCs) but increased memory B cells (MBCs). Tfh-GC B ce...
Chapter
In this method we illustrate how to amplify, sequence, and analyze antibody/immunoglobulin (IG) heavy-chain gene rearrangements from genomic DNA that is derived from bulk populations of cells by next-generation sequencing (NGS). We focus on human source material and illustrate how bulk gDNA-based sequencing can be used to examine clonal architectur...
Chapter
Adaptive immune receptor repertoires (AIRRs) are rich with information that can be mined for insights into the workings of the immune system. Gene usage, CDR3 properties, clonal lineage structure, and sequence diversity are all capable of revealing the dynamic immune response to perturbation by disease, vaccination, or other interventions. Here we...
Chapter
High-throughput sequencing of adaptive immune receptor repertoires (AIRR, i.e., IG and TR) has revolutionized the ability to carry out large-scale experiments to study the adaptive immune response. Since the method was first introduced in 2009, AIRR sequencing (AIRR-Seq) has been applied to survey the immune state of individuals, identify antigen-s...
Preprint
T memory stem cells (Tscm) are integral for effective immunotherapy and antitumor responses, but little is known about Tscm immunobiology in solid human tumors. Here we identify self-renewing and multipotent Tscm tumor-infiltrating lymphocytes (TILs) in human cancer and present a novel Tscm subset which expresses CD45RO, is derived from CD45RO- Tsc...
Article
Abstract Objectives B cell‐mediated immunity can be associated with favorable clinical outcomes in cancer patients. However, the mechanism and features of anti‐tumor immune responses are not well understood. In particular, how B cells expressing tumor‐specific antibodies are distributed (in the tumor vs. the circulation) has not been well defined....
Article
Full-text available
Antibody secreting plasma cells are made in response to a variety of pathogenic and commensal microbes. While all plasma cells express a core gene transcription program that allows them to secrete large quantities of immunoglobulin, unique transcriptional profiles are linked to plasma cells expressing different antibody isotypes. IgA expressing pla...
Article
Adjuvants are critical for improving the quality and magnitude of adaptive immune responses to vaccination. Lipid nanoparticle (LNP)-encapsulated nucleoside-modified mRNA vaccines have shown great efficacy against SARS-CoV-2, but the mechanism of action of this vaccine platform is not well-characterized. Using influenza virus and SARS-CoV-2 mRNA an...
Article
Full-text available
The persistence of anti-viral immunity is essential for protection and exhibits profound heterogeneity across individuals. Here, we elucidate the factors that shape maintenance and function of anti-viral T cell immunity in the body by comprehensive profiling of virus-specific T cells across blood, lymphoid organs, and mucosal tissues of organ donor...
Article
Full-text available
Immune memory after vaccination Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has proven highly effective at preventing severe COVID-19. However, the evolution of viral variants, and waning antibody levels over time, raise questions regarding the longevity of vaccine-induced immune protection. Goel et al . examine...
Article
Castleman disease (CD) represents a group of rare, heterogeneous and poorly understood disorders that share characteristic histopathological features. Unicentric CD (UCD) typically involves a single enlarged lymph node whereas multicentric CD (MCD) involves multiple lymph node stations. To understand the cellular basis of CD, we undertook a multi-p...
Preprint
Full-text available
SARS-CoV-2 mRNA vaccines have shown remarkable efficacy, especially in preventing severe illness and hospitalization. However, the emergence of several variants of concern and reports of declining antibody levels have raised uncertainty about the durability of immune memory following vaccination. In this study, we longitudinally profiled both antib...
Article
Full-text available
Differences in immune responses to viruses and autoimmune diseases such as systemic lupus erythematosus (SLE) can show sexual dimorphism. Age-associated B cells (ABC) are a population of CD11c ⁺ T-bet ⁺ B cells critical for antiviral responses and autoimmune disorders. Absence of DEF6 and SWAP-70, two homologous guanine exchange factors, in double-...
Article
Full-text available
Background Immune-mediated protection is mediated by T cells expressing pathogen-specific T cell antigen receptors (TCR) that are maintained at diverse sites of infection as tissue-resident memory T cells (TRM) or that disseminate as circulating effector-memory (TEM), central memory (TCM), or terminal effector (TEMRA) subsets in blood and tissues....
Article
Patients lacking functional adenosine deaminase activity suffer from severe combined immunodeficiency (ADA SCID), which can be treated with ADA enzyme replacement therapy (ERT), allogeneic hematopoietic stem cell transplantation (HSCT), or autologous HSCT with gene-corrected cells (gene therapy-GT). A cohort of 10 ADA SCID patients, aged 3 months t...
Article
Full-text available
Novel mRNA vaccines for SARS-CoV-2 have been authorized for emergency use. Despite their efficacy in clinical trials, data on mRNA vaccine-induced immune responses are mostly limited to serological analyses. Here, we interrogated antibody and antigen-specific memory B cells over time in 33 SARS-CoV-2 naïve and 11 SARS-CoV-2 recovered subjects. SARS...
Article
Full-text available
Antibodies that neutralize SARS-CoV-2, are thought to provide the most immediate and effective treatment for those severely afflicted by this virus. Because coronavirus potentially diversifies by mutation, broadly neutralizing antibodies are especially sought. Here we report a novel approach to rapid generation of potent broadly neutralizing human...
Article
In humans receiving intestinal transplantation (ITx), long-term multilineage blood chimerism often develops. Donor T cell macrochimerism (≥4%) frequently occurs without graft-versus-host disease (GVHD) and is associated with reduced rejection. Here we demonstrate that patients with macrochimerism had high graft-versus-host (GvH) to host-versus-graf...
Article
Ahmed and colleagues recently described a novel hybrid lymphocyte expressing both a B and T cell receptor, termed double expresser (DE) cells. DE cells in blood of type 1 diabetes (T1D) subjects were present at increased numbers and enriched for a public B cell clonotype. Here, we attempted to reproduce these findings. While we could identify DE ce...
Article
Objectives: Kikuchi-Fujimoto disease (KFD) is a self-limited lymphadenitis of unclear etiology. We aimed to further characterize this disease in pediatric patients, including evaluation of the CD123 immunohistochemical (IHC) staining and investigation of potential immunologic and infectious causes. Methods: Seventeen KFD cases and 12 controls we...
Preprint
Full-text available
Sex differences characterize immune responses to viruses and autoimmune diseases like SLE. ABCs are an emerging population of CD11c+ T-bet+ B cells critical for antiviral responses and autoimmune disorders. DEF6 and SWAP70, are two homologous molecules whose combined absence in double-knock-out mice (DKOs) leads to a lupus syndrome in females marke...
Article
In this issue of Cell Host & Microbe, Nielsen and colleagues sequence antibody repertoires of patients with severe COVID-19 to reveal potentially convergent features on the background of a larger, polyclonal response. Their findings suggest that, as databases improve, it may be possible to monitor virus-specific B cells after infection or vaccinati...
Preprint
Full-text available
Although critical illness has been associated with SARS-CoV-2-induced hyperinflammation, the immune correlates of severe COVID-19 remain unclear. Here, we comprehensively analyzed peripheral blood immune perturbations in 42 SARS-CoV-2 infected and recovered individuals. We identified broad changes in neutrophils, NK cells, and monocytes during seve...
Article
B cell subsets expressing the transcription factor T-bet are associated with humoral immune responses and autoimmunity. Here, we examined the anatomic distribution, clonal relationships, and functional properties of T-bet⁺ and T-bet⁻ memory B cells (MBCs) in the context of the influenza-specific immune response. In mice, both T-bet⁻ and T-bet⁺ hema...
Article
Full-text available
Transformation of follicular lymphoma (FL) into B-cell lymphoblastic lymphoma/leukemia (LL) is rare and results in greatly increased aggressiveness of clinical course. Here we present extensive molecular analysis of this unusual transformation, including immunoglobulin (Ig) gene rearrangement studies, cytogenetic analysis, and whole exome sequencin...
Article
The B cell response to Ehrlichia muris is dominated by plasmablasts (PBs), with few-if any-germinal centers (GCs), yet it generates protective immunoglobulin M (IgM) memory B cells (MBCs) that express the transcription factor T-bet and harbor V-region mutations. Because Ehrlichia prominently infects the liver, we investigated the nature of liver B...
Data
SRA accession information for the five samples used in the germline assignment comparison between ImmuneDB and MiXCR.
Data
SRA accession information for the 19 samples used in the clonal inference comparison between ImmuneDB and MiXCR.
Article
Translating studies on T cell function and modulation from mouse models to humans requires extrapolating in vivo results on mouse T cell responses in lymphoid organs (spleen and lymph nodes [LN]) to human peripheral blood T cells. However, our understanding of T cell responses in human lymphoid sites and their relation to peripheral blood remains s...
Data
Fasta files of IMGT human JH genes used for germline gene assignment.
Data
Fasta files of IMGT human VH genes used for germline gene assignment.
Article
Full-text available
Background The genes that produce antibodies and the immune receptors expressed on lymphocytes are not germline encoded; rather, they are somatically generated in each developing lymphocyte by a process called V(D)J recombination, which assembles specific, independent gene segments into mature composite genes. The full set of composite genes in an...
Article
As high-throughput sequencing of B cells becomes more common, the need for tools to analyze the large quantity of data also increases. This paper introduces ImmuneDB, a system for analyzing vast amounts of IGHV sequences and exploring the resulting data. It can take as input raw FASTA/FASTQ data, identify genes, determine clones, construct lineages...
Presentation
Full-text available
The Biopython Project is a long-running distributed collaborative effort, supported by the Open Bioinformatics Foundation, which develops a freely available Python library for biological computation.We present here details of the latest Biopython release - version 1.66. New features include: extended Bio.KEGG and Bio.Graphics modules to support dra...
Conference Paper
Full-text available
This work applies a distributed algorithm utilizing Markov Random Fields (MRFs) to the problem of dynamically selecting Session and Transport layer protocols in challenged networks such as mobile ad-hoc networks. It motivates the problem by identifying the primary network properties which affect Message Delivery Ratio (MDR) in networks with varying...
Conference Paper
Full-text available
Maintaining a consistent set of state information across applications in tactical edge, mobile ad-hoc networks (MANETs) is a challenging, yet mission-critical task. This paper analyzes the performance and effectiveness of eight approaches to data persistence with three different persistence requirements. This is done by introducing COPE, a middlewa...

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