Publications by authors named "Derek Reiman"

Background: Early and precise diagnosis is vital to improving patient outcomes and reducing morbidity. In resource-limited settings, cancer diagnosis is often challenging due to shortages of expert pathologists. We assess the effectiveness of general-purpose pathology foundation models (FM) for the diagnosis and annotation of nonmelanoma skin cancer (NMSC) in resource-limited settings.

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Because large brains are energetically expensive, they are associated with metabolic traits that facilitate energy availability across vertebrates. However, the biological underpinnings driving these traits are not known. Given its role in regulating host metabolism in disease studies, we hypothesized that the gut microbiome contributes to variation in normal cross-vertebrate species differences in metabolism, including those associated with the brain's energetic requirements.

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Autoimmune diseases such as systemic lupus erythematosus (SLE) display a strong female bias. Although sex hormones have been associated with protecting males from autoimmunity, the molecular mechanisms are incompletely understood. Here we report that androgen receptor (AR) expressed in T cells regulates genes involved in T cell activation directly, or indirectly via controlling other transcription factors.

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Article Synopsis
  • Single-cell RNA sequencing (scRNA-seq) allows in-depth analysis of B cell evolution during immune responses, highlighting processes like somatic hypermutation (SHM) and class switch recombination (CSR).
  • The newly introduced TRIBAL algorithm focuses on accurately reconstructing B cell evolutionary histories by considering both SHM and CSR, addressing limitations of prior phylogenetic methods.
  • Simulations and real-world applications show TRIBAL outperforms existing approaches, offering more accurate lineage trees and insights into B cell responses, which can enhance vaccine development and therapeutic antibody identification.
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Commensal microbes have the capacity to affect development and severity of autoimmune diseases. Germ-free (GF) animals have proven to be a fine tool to obtain definitive answers to the queries about the microbial role in these diseases. Moreover, GF and gnotobiotic animals can be used to dissect the complex symptoms and determine which are regulated (enhanced or attenuated) by microbes.

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B cells are a critical component of the adaptive immune system, responsible for producing antibodies that help protect the body from infections and foreign substances. Single cell RNA-sequencing (scRNA-seq) has allowed for both profiling of B cell receptor (BCR) sequences and gene expression. However, understanding the adaptive and evolutionary mechanisms of B cells in response to specific stimuli remains a significant challenge in the field of immunology.

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  • A diet high in hydrolyzed casein can protect against the development of type 1 diabetes (T1D) in mice by improving insulin-producing cell function and reducing autoimmune activation.
  • The addition of gluten, when digested by the microbe Enterococcus faecalis, can trigger T1D by creating peptides that activate T cells and enhance the immune response.
  • Research shows that certain dietary interventions could potentially help in preventing autoimmune diseases like T1D in humans by understanding the role of diet and gut microbes.
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The alterations in myometrial biology during labor are not well understood. The myometrium is the contractile portion of the uterus and contributes to labor, a process that may be regulated by the steroid hormone progesterone. Thus, human myometrial tissues from term pregnant in-active-labor (TIL) and term pregnant not-in-labor (TNIL) subjects were used for genome-wide analyses to elucidate potential future preventive or therapeutic targets involved in the regulation of labor.

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Background & Aims: Normal gestation involves a reprogramming of the maternal gut microbiome (GM) that contributes to maternal metabolic changes by unclear mechanisms. This study aimed to understand the mechanistic underpinnings of the GM-maternal metabolism interaction.

Methods: The GM and plasma metabolome of CD1, NIH-Swiss, and C57 mice were analyzed with the use of 16S rRNA sequencing and untargeted liquid chromatography-mass spectrometry throughout gestation.

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The accuracy of methods for assembling transcripts from short-read RNA sequencing data is limited by the lack of long-range information. Here we introduce Ladder-seq, an approach that separates transcripts according to their lengths before sequencing and uses the additional information to improve the quantification and assembly of transcripts. Using simulated data, we show that a kallisto algorithm extended to process Ladder-seq data quantifies transcripts of complex genes with substantially higher accuracy than conventional kallisto.

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The advance in microbiome and metabolome studies has generated rich omics data revealing the involvement of the microbial community in host disease pathogenesis through interactions with their host at a metabolic level. However, the computational tools to uncover these relationships are just emerging. Here, we present MiMeNet, a neural network framework for modeling microbe-metabolite relationships.

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Single cell RNA sequencing (scRNAseq) can be used to infer a temporal ordering of cellular states. Current methods for the inference of cellular trajectories rely on unbiased dimensionality reduction techniques. However, such biologically agnostic ordering can prove difficult for modeling complex developmental or differentiation processes.

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Accurate prediction of the host phenotypes from a microbial sample and identification of the associated microbial markers are important in understanding the impact of the microbiome on the pathogenesis and progression of various diseases within the host. A deep learning tool, PopPhy-CNN, has been developed for the task of predicting host phenotypes using a convolutional neural network (CNN). By representing samples as annotated taxonomic trees and further representing these trees as matrices, PopPhy-CNN utilizes the CNN's innate ability to explore locally similar microbes on the taxonomic tree.

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Accurate prediction of the host phenotype from a metagenomic sample and identification of the associated microbial markers are important in understanding potential host-microbiome interactions related to disease initiation and progression. We introduce PopPhy-CNN, a novel convolutional neural network (CNN) learning framework that effectively exploits phylogenetic structure in microbial taxa for host phenotype prediction. Our approach takes an input format of a 2D matrix representing the phylogenetic tree populated with the relative abundance of microbial taxa in a metagenomic sample.

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Patient responses to cancer immunotherapy are shaped by their unique genomic landscape and tumor microenvironment. Clinical advances in immunotherapy are changing the treatment landscape by enhancing a patient's immune response to eliminate cancer cells. While this provides potentially beneficial treatment options for many patients, only a minority of these patients respond to immunotherapy.

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Food allergy is usually difficult to diagnose in early life, and the inability to diagnose patients with atopic diseases at an early age may lead to severe complications. Numerous studies have suggested an association between the infant gut microbiome and development of allergy. In this work, we investigated the capacity of Long Short-Term Memory (LSTM) networks to predict food allergies in early life (0-3 years) from subjects' longitudinal gut microbiome profiles.

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The microbiome has been shown to have an impact on the development of various diseases in the host. Being able to make an accurate prediction of the phenotype of a genomic sample based on its microbial taxonomic abundance profile is an important problem for personalized medicine. In this paper, we examine the potential of using a deep learning framework, a convolutional neural network (CNN), for such a prediction.

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