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B cell clonal expansion is correlated with antigen-specificity in young but not old mice
(2021)bioRxivAging of the humoral immune response has been shown to affect its critical role in defending the host from a variety of pathogens. Technical limitations have nevertheless made it challenging to investigate the relationship between genotype and phenotype of antibody repertoires in the context of aging. We therefore performed single-cell sequencing of over 95,000 B cells to simultaneously investigate B cell receptor (BCR) repertoires and ...Working Paper -
High-throughput identification of RNA localization elements reveals a regulatory role for A/G rich sequences
(2021)bioRxivHundreds of RNAs are enriched in the projections of neuronal cells. For the vast majority of them, though, the sequence elements within them that regulate their localization are unknown. To identify RNA elements capable of directing transcripts to neurites, we designed and deployed a massively parallel reporter assay that tested the localization regulatory ability of thousands of sequence fragments drawn from endogenous mouse 3′ UTRs. We ...Working Paper -
The Physiological Landscape and Specificity of Antibody Repertoires
(2021)bioRxivDiverse antibody repertoires spanning multiple lymphoid organs (e.g., bone marrow, spleen, lymph nodes) form the foundation of protective humoral immunity. Changes in their composition across lymphoid organs are a consequence of B-cell selection and migration events leading to a highly dynamic and unique physiological landscape of antibody repertoires upon antigenic challenge (e.g., vaccination). However, to what extent B cells encoding ...Working Paper -
The Chloroflexi supergroup is metabolically diverse and representatives have novel genes for non-photosynthesis based CO2 fixation
(2021)bioRxivThe Chloroflexi superphylum have been investigated primarily from the perspective of reductive dehalogenation of toxic compounds, anaerobic photosynthesis and wastewater treatment, but remain relatively little studied compared to their close relatives within the larger Terrabacteria group, including Cyanobacteria, Actinobacteria, and Firmicutes. Here, we conducted a detailed phylogenetic analysis of the phylum Chloroflexota, the ...Working Paper -
Clonally expanded virus-specific CD8 T cells acquire diverse transcriptional phenotypes during acute, chronic, and latent infections
(2021)bioRxivCD8+ T cells play a crucial role in the control and resolution of viral infections and can adopt a wide range of phenotypes and effector functions depending on the inflammatory context and the duration and extent of antigen exposure. Similarly, viral infections can exert diverse selective pressures on populations of clonally related T cells. Technical limitations have nevertheless made it challenging to investigate the relationship between ...Working Paper -
Phenotypic determinism and stochasticity in antibody repertoires of clonally expanded plasma cells
(2021)bioRxivThe capacity of humoral B cell-mediated immunity to effectively respond to and protect against pathogenic infections is largely driven by the presence of a diverse repertoire of polyclonal antibodies in the serum, which are produced by plasma cells (PCs).1,2 Recent studies have started to reveal the balance between deterministic mechanisms and stochasticity of antibody repertoires on a genotypic level (i.e., clonal diversity, somatic ...Working Paper -
Comparison of RNA extraction methods for the detection of SARS-CoV-2 by RT-PCR
(2020)medRxivWorking Paper -
Distinct microRNA signature in human serum and germline after childhood trauma
(2020)medRxivTraumatic experiences during childhood can persistently alter mental and physical health in humans and have been implicated in transmission of symptoms to the progeny in animal models. Molecular evidence from these models implicates epigenetic/non-genetic factors, such as microRNAs (miRNAs), in the expression of trauma-induced symptoms and their transmission to the offspring. To confirm these findings in humans, we assembled three cohorts ...Working Paper -
Defining the Pandemic at the State Level: Sequence-Based Epidemiology of the SARS-CoV-2 virus by the Arizona COVID-19 Genomics Union (ACGU)
(2020)medRxivIn December of 2019, a novel coronavirus, SARS-CoV-2, emerged in the city of Wuhan, China causing severe morbidity and mortality. Since then, the virus has swept across the globe causing millions of confirmed infections and hundreds of thousands of deaths. To better understand the nature of the pandemic and the introduction and spread of the virus in Arizona, we sequenced viral genomes from clinical samples tested at the TGen North Clinical ...Working Paper -