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1. Machine learning‐based identification of general transcriptional predictors for plant disease

   https://doi.org/10.1111/nph.20264  

   Sia, Jayson; Zhang, Wei; Cheng, Mingxi; Bogdan, Paul; Cook, David E (January 2025, New Phytologist)

   This study investigated the generalizability of Arabidopsis thaliana immune responses across diverse pathogens, including Botrytis cinerea, Sclerotinia sclerotiorum, and Pseudomonas syringae, using a data-driven, machine learning approach. Machine learning models were trained to predict disease development from early transcriptional responses. Feature selection techniques based on network science and topology were used to train models employing only a fraction of the transcriptome. Machine learning models trained on one pathosystem where then validated by predicting disease development in new pathosystems. The identified feature selection gene sets were enriched for pathways related to biotic, abiotic, and stress responses, though the specific genes involved differed between feature sets. This suggests common immune responses to diverse pathogens that operate via different gene sets.The study demonstrates that machine learning can uncover both established and novel components of the plant's immune response, offering insights into disease resistance mechanisms. These predictive models highlight the potential to advance our understanding of multigenic outcomes in plant immunity and can be further refined for applications in disease prediction. 

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2. Immune System Promiscuity in Human and Nonhuman Primate Evolution

   https://doi.org/10.13110/humanbiology.90.4.01  

   Brinkworth, Jessica F.; Babbitt, Courtney (January 2018, Human biology)

   null (Ed.)

   Many genes that respond to infection have functions outside of immunity and have been found to be under natural selection. Pathogens may therefore incidentally alter nonimmune physiology through engagement with immune system genes. This raises a logical question of how genetically promiscuous the immune system is, here defined as how heavily cross-referenced the immune system is into other physiological systems. This work examined immune gene promiscuity across physiological systems in primates by assessing the baseline (unperturbed) expression of key tissue and cell types for differences, and primate genomes for signatures of selection. These efforts revealed “immune” gene expression to be cross-referenced extensively in other physiological systems in primates. When immune and nonimmune tissues diverge in expression, the differentially expressed genes at baseline are enriched for cell biological activities not immediately identifiable as immune function based. Individual comparisons of immune and nonimmune tissues in primates revealed low divergence in gene expression between tissues, with the exception of whole blood. Immune gene promiscuity increases over evolutionary time, with hominoids exhibiting the most cross-referencing of such genes among primates. An assessment of genetic sequences also found positive selection in the coding regions of differentially expressed genes between tissues functionally associated with immunity. This suggests that, with increasing promiscuity, divergent gene expression between the immune system and other physiological systems tends to be adaptive and enriched for immune functions in hominoids. 

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3. Immune System Promiscuity in Human and Nonhuman Primate Evolution

   Brinkworth, J.F.; Babbitt, C.C. (October 2019, Human biology)

   Many genes that respond to infection have functions outside of immunity and have been found to be under natural selection. Pathogens may therefore incidentally alter nonimmune physiology through engagement with immune system genes. This raises a logical question of how genetically promiscuous the immune system is, here defijined as how heavily cross-referenced the immune system is into other physiological systems. This work examined immune gene promiscuity across physiological systems in primates by assessing the baseline (unperturbed) expression of key tissue and cell types for diffferences, and primate genomes for signatures of selection. These effforts revealed “immune” gene expression to be cross-referenced extensively in other physiological systems in primates. When immune and nonim-mune tissues diverge in expression, the diffferentially expressed genes at baseline are enriched for cell biological activities not immediately identifijiable as immune function based. Individual comparisons of immune and nonimmune tissues in primates revealed low divergence in gene expression between tissues, with the exception of whole blood. Immune gene promiscuity increases over evolutionary time, with hominoids exhibiting the most cross-referencing of such genes among primates. An assessment of genetic sequences also found positive selection in the coding regions of diffferentially expressed genes between tissues functionally associated with immunity. This suggests that, with increasing promiscuity, divergent gene expression between the immune system and other physiological systems tends to be adaptive and enriched for immune functions in hominoids. 

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4. Immune Gene Expression Covaries with Gut Microbiome Composition in Stickleback

   https://doi.org/10.1128/mBio.00145-21  

   Fuess, Lauren E.; den Haan, Stijn; Ling, Fei; Weber, Jesse N.; Steinel, Natalie C.; Bolnick, Daniel I. (January 2021, mBio)

   Rawls, John F.; McFall-Ngai, Margaret J. (Ed.)

   ABSTRACT Commensal microbial communities have immense effects on their vertebrate hosts, contributing to a number of physiological functions, as well as host fitness. In particular, host immunity is strongly linked to microbiota composition through poorly understood bi-directional links. Gene expression may be a potential mediator of these links between microbial communities and host function. However, few studies have investigated connections between microbiota composition and expression of host immune genes in complex systems. Here, we leverage a large study of laboratory-raised fish from the species Gasterosteus aculeatus (three-spined stickleback) to document correlations between gene expression and microbiome composition. First, we examined correlations between microbiome alpha diversity and gene expression. Our results demonstrate robust positive associations between microbial alpha diversity and expression of host immune genes. Next, we examined correlations between host gene expression and abundance of microbial taxa. We identified 15 microbial families that were highly correlated with host gene expression. These families were all tightly correlated with host expression of immune genes and processes, falling into one of three categories—those positively correlated, negatively correlated, and neutrally related to immune processes. Furthermore, we highlight several important immune processes that are commonly associated with the abundance of these taxa, including both macrophage and B cell functions. Further functional characterization of microbial taxa will help disentangle the mechanisms of the correlations described here. In sum, our study supports prevailing hypotheses of intimate links between host immunity and gut microbiome composition. IMPORTANCE Here, we document associations between host gene expression and gut microbiome composition in a nonmammalian vertebrate species. We highlight associations between expression of immune genes and both microbiome diversity and abundance of specific microbial taxa. These findings support other findings from model systems which have suggested that gut microbiome composition and host immunity are intimately linked. Furthermore, we demonstrate that these correlations are truly systemic; the gene expression detailed here was collected from an important fish immune organ (the head kidney) that is anatomically distant from the gut. This emphasizes the systemic impact of connections between gut microbiota and host immune function. Our work is a significant advancement in the understanding of immune-microbiome links in nonmodel, natural systems. 

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5. Large‐scale Genome sampling reveals unique immunity and metabolic adaptations in Bats

   https://doi.org/10.1111/mec.16027  

   Moreno Santillán, Diana D.; Lama, Tanya M.; Gutierrez Guerrero, Yocelyn T.; Brown, Alexis M.; Donat, Paul; Zhao, Huabin; Rossiter, Stephen J.; Yohe, Laurel R.; Potter, Joshua H.; Teeling, Emma C.; et al (January 2021, Molecular Ecology)

   null (Ed.)

   Comprising more than 1,400 species, bats possess adaptations unique among mammals including powered flight, unexpected longevity, and extraordinary immunity. Some of the molecular mechanisms underlying these unique adaptations includes DNA repair, metabolism and immunity. However, analyses have been limited to a few divergent lineages, reducing the scope of inferences on gene family evolution across the Order Chiroptera. We conducted an exhaustive comparative genomic study of 37 bat species, one generated in this study, encompassing a large number of lineages, with a particular emphasis on multi-gene family evolution across immune and metabolic genes. In agreement with previous analyses, we found lineage-specific expansions of the APOBEC3 and MHC-I gene families, and loss of the proinflammatory PYHIN gene family. We inferred more than 1,000 gene losses unique to bats, including genes involved in the regulation of inflammasome pathways such as epithelial defense receptors, the natural killer gene complex and the interferon-gamma induced pathway. Gene set enrichment analyses revealed genes lost in bats are involved in defense response against pathogen-associated molecular patterns and damage-associated molecular patterns. Gene family evolution and selection analyses indicate bats have evolved fundamental functional differences compared to other mammals in both innate and adaptive immune system, with the potential to enhance anti-viral immune response while dampening inflammatory signaling. In addition, metabolic genes have experienced repeated expansions related to convergent shifts to plant-based diets. Our analyses support the hypothesis that, in tandem with flight, ancestral bats had evolved a unique set of immune adaptations whose functional implications remain to be explored. 

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