Top 10 Biorxiv Papers Today in Immunology


2.013 Mikeys
#1. ImmuneRegulation: A web-based tool for identifying human immune regulatory elements
Selim Kalayci, Myvizhi Esai Selvan, Irene Ramos, Chris Cotsapas, Ruth R. Montgomery, Gregory Poland, Bali Pulendran, John Tsang, Robert J. Klein, Zeynep H Gumus
Humans can vary considerably in their healthy immune phenotypes and in their immune responses to various stimuli. We have developed an interactive web-based tool, ImmuneRegulation, to enable discovery of human regulatory elements that drive some of the phenotypic differences observed in gene expression profiles. ImmuneRegulation currently provides the largest centrally integrated resource available in the literature on transcriptome regulation in whole blood and blood cell types, including genotype data from 23,040 individuals, with associated gene expression data from 30,562 experiments, that provide genetic variant-gene expression associations on ~200 million eQTLs. In addition, it includes 14 million transcription factor (TF) binding region hits extracted from 1945 TF ChIP-seq peaks and the latest GWAS catalog of 67,230 published SNP-trait associations. Users can interactively explore ImmuneRegulation to visualize and discover associations between their gene(s) of interest and their regulators (genetic variants or transcription...
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biorxivpreprint: ImmuneRegulation: A web-based tool for identifying human immune regulatory elements https://t.co/gH4PrYspAh #bioRxiv
ZeynepHG: A preprint of our ImmuneRegulation portal is now in bioRxiv: ImmuneRegulation: a web-based interactive tool for identifying human immune regulatory elements @hipc https://t.co/bfnJWCQiby
CyrilPedia: 'ImmuneRegulation: A web-based tool for identifying human immune regulatory elements' https://t.co/JoD8WMsL29
mace_em: ImmuneRegulation: A web-based tool for identifying human immune regulatory elements https://t.co/9Rqse04uHp
MalmbergLab: RT @mace_em: ImmuneRegulation: A web-based tool for identifying human immune regulatory elements https://t.co/9Rqse04uHp
hotirishmonkey: RT @mace_em: ImmuneRegulation: A web-based tool for identifying human immune regulatory elements https://t.co/9Rqse04uHp
VikiLovesFACS: RT @mace_em: ImmuneRegulation: A web-based tool for identifying human immune regulatory elements https://t.co/9Rqse04uHp
nachogonzalez: RT @mace_em: ImmuneRegulation: A web-based tool for identifying human immune regulatory elements https://t.co/9Rqse04uHp
QuirinHammer: RT @mace_em: ImmuneRegulation: A web-based tool for identifying human immune regulatory elements https://t.co/9Rqse04uHp
JustinGunesch: RT @mace_em: ImmuneRegulation: A web-based tool for identifying human immune regulatory elements https://t.co/9Rqse04uHp
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Authors: 10
Total Words: 4784
Unqiue Words: 1613

2.013 Mikeys
#2. Global transcriptional regulation of innate immunity in C. elegans
Marissa Fletcher, Erik J Tillman, Vincent L Butty, Stuart S Levine, Dennis H. Kim
The nematode Caenorhabditis elegans has emerged as a genetically tractable animal host in which to study evolutionarily conserved mechanisms of innate immune signaling. We previously showed that the PMK-1 p38 mitogen-activated protein kinase (MAPK) pathway regulates innate immunity of C. elegans through phosphorylation of the CREB/ATF bZIP transcription factor, ATF-7. Here, we have undertaken a genomic analysis of the transcriptional response of C. elegans to infection by Pseudomonas aeruginosa, combining genome-wide expression analysis by RNA-seq with ATF-7 chromatin immunoprecipitation followed by sequencing (ChIP-Seq). We observe that PMK-1-ATF-7 activity regulates a majority of all genes induced by pathogen infection, and observe ATF-7 occupancy in regulatory regions of pathogen-induced genes in a PMK-1-dependent manner. Moreover, functional analysis of a subset of these ATF-7-regulated pathogen-induced target genes supports a direct role for this transcriptional response in host defense. The genome-wide regulation through...
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biorxivpreprint: Global transcriptional regulation of innate immunity in C. elegans https://t.co/SDKn951TP0 #bioRxiv
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Authors: 5
Total Words: 7387
Unqiue Words: 2610

2.003 Mikeys
#3. Skin inflammation driven by differentiation of quiescent tissue-resident ILCs into a spectrum of pathogenic effectors
Piotr Bielecki, Samantha J Riesenfled, Monika S Kowalczyk, Maria C Amezcua Vesely, Lina Kroehling, Parastou Yaghoubi, Danielle Dionne, Abigail Jarret, Holly R Steach, Heather M McGee, Caroline B. M. Porter, Paula Licona-Limon, Will Bailis, Ruaidhri Jackson, Nicola Gagliani, Richard M Locksley, Aviv Regev, Richard A Flavell
Psoriasis pathology is driven by the type 3 cytokines IL-17 and Il-22, but little is understood about the dynamics that initiate alterations in tissue homeostasis. Here, we use mouse models, single-cell RNA-seq (scRNA-seq), computational inference and cell lineage mapping to show that psoriasis induction reconfigures the functionality of skin-resident ILCs to initiate disease. Tissue-resident ILCs amplified an initial IL-23 trigger and were sufficient, without circulatory ILCs, to drive pathology, indicating that ILC tissue remodeling initiates psoriasis. Skin ILCs expressed type 2 cytokines IL-5 and IL-13 in steady state, but were epigenetically poised to become ILC3-like cells. ScRNA-seq profiles of ILCs from psoriatic and naive skin of wild type (WT) and Rag1-/- mice form a dense continuum, consistent with this model of fluid ILC states. We inferred biological "topics" underlying these states and their relative importance in each cell with a generative model of latent Dirichlet allocation, showing that ILCs from untreated skin...
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CyrilPedia: Fm @FlavellLab et al "Here, we use mouse models, scRNA-seq, computational inference and cell lineage mapping to show that psoriasis induction reconfigures the functionality of skin-resident ILCs to initiate disease" https://t.co/8ZkxjEKpxn
GMagri_Immuno: Skin inflammation driven by differentiation of quiescent tissue-resident ILCs into a spectrum of pathogenic effectors https://t.co/TT2QwlQDx2
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Authors: 18
Total Words: 13695
Unqiue Words: 4473

1.998 Mikeys
#4. Penaeidins are a novel family of antiviral effectors against WSSV in shrimp
Bang Xiao, Qihui Fu, Shengwen Niu, Haoyang Li, Kai Lŭ, Sheng Wang, Bin Yin, Shao-Ping Weng, Chaozheng Li, Jian-Guo He
Penaeidins are members of a family of key effectors with broad anti-bacterial activities in penaeid shrimp. However, the function of penaeidins in antiviral immunity is rarely reported and remains largely unknown. Herein, we uncovered that penaeidins are a novel family of antiviral effectors against white spot syndrome virus (WSSV). Firstly, RNAi in vivo mediated knockdown of each penaeidin from four identified penaeidins from Litopenaeus vannamei resulted in elevated viral loads and rendered shrimp more susceptible to WSSV, whilst the phenotype of survival rate in penaeidin-silenced shrimp can be rescued via the injection of recombinant penaeidin proteins. Moreover, pull-down assays demonstrated the conserved PEN domain of penaeidin was able to interact with WSSV structural proteins. Furthermore, we observed that colloidal gold-labeled penaeidins were located on the outer surface of the WSSV virion. By infection-blocking assay, we observed that hemocytes had lower viral infection rates in the group of WSSV preincubated with...
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Authors: 10
Total Words: 13408
Unqiue Words: 3965

1.987 Mikeys
#5. How a well-adapting immune system remembers
Andreas Mayer, Vijay Balasubramanian, Aleksandra M Walczak, Thierry Mora
An adaptive agent predicting the future state of an environment must weigh trust in new observations against prior experiences. In this light, we propose a view of the adaptive immune system as a dynamic Bayesian machinery that updates its memory repertoire by balancing evidence from new pathogen encounters against past experience of infection to predict and prepare for future threats. This framework links the observed initial rapid increase of the memory pool early in life followed by a mid-life plateau to the ease of learning salient features of sparse environments. We also derive a modulated memory pool update rule in agreement with current vaccine response experiments. Our results suggest that pathogenic environments are sparse and that memory repertoires significantly decrease infection costs even with moderate sampling. The predicted optimal update scheme maps onto commonly considered competitive dynamics for antigen receptors.
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Authors: 4
Total Words: 14158
Unqiue Words: 3293

0.0 Mikeys
#6. The landscape of S100B+ and HLA-DR+ dendritic cell subsets in tonsils at the single cell level via high-parameter mapping
Maddalena Maria Bolognesi, Francesca Maria Bosisio, Marco Manzoni, Denis Schapiro, Riccardo Tagliabue, Mario Faretta, Carlo Parravicini, Ann M Haberman, Giorgio Cattoretti
Dendritic cells (DC) (classic, plasmacytoid, inflammatory) are an intense focus of interest because of their role in inflammation, autoimmunity, vaccination and cancer. We present a tissue-based classification of human DC subsets in tonsils with a high parameter (>40 markers) immunofluorescent approach, cell type-specific image segmentation and the use of bioinformatics platforms. Through this deep phenotypic and spatial examination, classic cDC1, cDC2, pDC subsets have been further refined and a novel subset of DC co-expressing IRF4 and IRF8 identified. Based on unique tissue locations within the tonsil, and close interactions with T cells (cDC1) or B cells (cDC2), DC subsets can be further subdivided by correlative phenotypic changes associated with these interactions. In addition, monocytes and macrophages expressing HLA-DR or S100AB are identified and localized in the tissue. This study thus provides a whole tissue in situ catalog of human DC subsets and their cellular interactions within spatially defined niches.
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biorxivpreprint: The landscape of S100B+ and HLA-DR+ dendritic cell subsets in tonsils at the single cell level via high-parameter mapping https://t.co/VFE6lCcNCX #bioRxiv
mace_em: The landscape of S100B+ and HLA-DR+ dendritic cell subsets in tonsils at the single cell level via high-parameter mapping https://t.co/sRAFIeNpbt
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Authors: 9
Total Words: 19131
Unqiue Words: 4786

0.0 Mikeys
#7. Overcoming non-small cell lung cancer radiation resistance by modulating the tumor-immune ecosystem
Sara Nizzero, Juan Carlos L. Alfonso, Arturo Alvarez-Arenas, Inom Mirzaev, Ioannis K. Zervantonakis, Thomas Lewin, Anupam Rishi, Elena Piretto, Tanvi V. Joshi, Daniel N. Santiago, Aleksandra M. Karolak, Rachel Howard, Heiko Enderling, Florian A. Karreth, Javier Torres-Roca
Non-small-cell lung cancer is the leading cause of cancer death worldwide. Although radiotherapy is an effective treatment choice for early-stage cases, the 5-year survival rate of patients diagnosed in late-stages remains poor. Increasing evidence suggests that the local and systemic effects of radiotherapy dependent on the induced anti-tumor immune responses. We believe that an educated adaptation of radiotherapy plans based not only on the induced immune responses, but also on the tumor-immune ecosystem composition at the beginning of treatment might increase local tumor control. We propose two different mathematical models to evaluate the potential of the tumor-immune context to inform adaptation of treatment plans with the aim of improving outcomes.
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Authors: 15
Total Words: 3501
Unqiue Words: 1500

0.0 Mikeys
#8. The concerted action of E2-2 and HEB is critical for early lymphoid specification
Thibault Bouderlique, Lucia Peňa Perez, Shabnam Kharazi, Miriam Hils, Xiaoze Li, Aleksandra Krstic, Ayla de Paepe, Christian Schachtrup, Charlotte Gustafsson, Dan Holmberg, Kristina Schachtrup, Robert Månsson
The apparition of adaptive immunity in Gnathostomata correlates with the expansion of the E-protein family to encompass E2-2, HEB and E2A. Within the family, E2-2 and HEB are more closely evolutionarily related but their concerted action in hematopoiesis remains to be explored. Here we show that the combined disruption of E2-2 and HEB results in failure to express the early lymphoid program in CLPs and a near complete block in B-cell development. In the thymus, ETPs were reduced and T-cell development perturbed, resulting in reduced CD4 T- and increased γδ T-cell numbers. In contrast, HSCs, erythro-myeloid progenitors and innate immune cells were unaffected showing that E2-2 and HEB are dispensable for the ancestral hematopoietic lineages. Taken together, this E-protein dependence suggests that the appearance of the full Gnathostomata E-protein repertoire was critical to reinforce the gene regulatory circuits that drove the emergence and expansion of the lineages constituting humoral immunity.
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Authors: 12
Total Words: 10409
Unqiue Words: 2923

0.0 Mikeys
#9. Local Attachment Explains Small-World-Like Properties of Fibroblastic Reticular Cell Networks in Lymph Nodes
Kasper M.W. Soekarjo, Johannes Textor, Rob J. De Boer
Fibroblastic reticular cells (FRCs) form a cellular network that serves as the structural backbone of lymph nodes and facilitates lymphocyte migration. This FRC network has been found to have small-world properties. Using a model based on geographical preferential attachment, we simulated the formation of a variety of cellular networks and show that similar small-world properties robustly emerge under such natural conditions. By estimating the parameters of this model, we generated FRC network representations with realistic topological properties. We found that these properties change markedly when the network is expanded from a thin slice to a 3D cube. Typical small-world properties were found to persist as network size was increased. The simulated networks were very similar to 2D and 3D lattice networks. According to the used metrics, these lattice networks also have small-world properties, indicating that lattice-likeness is sufficient to become classified as a small-world network. Our results explain why FRC networks have...
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biorxivpreprint: Local Attachment Explains Small-World-Like Properties of Fibroblastic Reticular Cell Networks in Lymph Nodes https://t.co/MLkHjLRzlh #bioRxiv
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Authors: 3
Total Words: 6005
Unqiue Words: 1641

0.0 Mikeys
#10. powerTCR: a model-based approach to comparative analysis of the clone size distribution of the T cell receptor repertoire
Hillary Koch, Dmytro Starenki, Sara J Cooper, Richard M Myers, Qunhua Li
Sequencing of the T cell receptor repertoire is a powerful tool for deeper study of immune response, but the unique structure of this type of data makes its meaningful quantification challenging. We introduce a new method, the Gamma-GPD spliced threshold model, to address this difficulty. This biologically interpretable model captures the distribution of the TCR repertoire, demonstrates stability across varying sequencing depths, and permits comparative analysis across any number of sampled individuals. We apply our method to several datasets and obtain insights regarding the differentiating features in the T cell receptor repertoire among sampled individuals across conditions. We have implemented our method in the open-source R package powerTCR.
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Authors: 5
Total Words: 9856
Unqiue Words: 2999

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