Biology subjects

Jiang, M.

Publications and source records attributed to Jiang, M..

At least 91 records · Page 5Linked to original sources

bioRxiv2023

coRIC map: a framework for the exploration of multifaceted subcellular RNA-binding proteins

The ability of RNA-binding proteins (RBPs) to form complexes with other biomolecules underpins a broad range of functions and remarkable structural properties. Understanding the precise spatiotemporal dynamics of RBPs and their interacting partners in the steady state and upon perturbation is key to deciphering these aspects. Here, we present the coRIC (compartmentalized RNA Interactome Capture) map, an experimental resource and analytical pipeline to study the subcellular dynamics of RBPs through multimodal dataset integration and machine learning. Using this approach, we have generated an atlas comprising 1,768 RBPs distributed in a broad panel of subcellular compartments and delineated their intermolecular and intercompartmental relationships. We have also defined the hierarchy of RBP-containing complexes at multiple scales across the cell, uncovering previously unknown functions of multiple RBPs. Furthermore, we have investigated the changes in RBP complex composition and subcellular distribution in response to C9ORF72 amyotrophic lateral sclerosis/frontotemporal dementia dipeptide repeats and DNA damage stress. The coRIC map provides a valuable new approach for defining the roles of RBPs in homeostasis and disease.

cell biology↗

bioRxiv2023

Dissecting signaling regulators driving AXL-mediated bypass resistance and associated phenotypes by phosphosite perturbations

Receptor tyrosine kinase (RTK)-targeted therapies are often effective but invariably limited by drug resistance. A major mechanism of acquired resistance involves "bypass" switching to alternative pathways driven by non-targeted RTKs that restore proliferation. One such RTK is AXL whose overexpression, frequently observed in bypass resistant tumors, drives both cell survival and associated malignant phenotypes such as epithelial-to-mesenchymal (EMT) transition and migration. However, the signaling molecules and pathways eliciting these responses have remained elusive. To explore these coordinated effects, we generated a panel of mutant lung adenocarcinoma PC9 cell lines in which each AXL intracellular tyrosine residue was mutated to phenylalanine. By integrating measurements of phosphorylation signaling and other phenotypic changes associated with resistance through multivariate modeling, we mapped signaling perturbations to specific resistant phenotypes. Our results suggest that AXL signaling can be summarized into two clusters associated with progressive disease and poor clinical outcomes in lung cancer patients. These clusters displayed favorable Abl1 and SFK motifs and their phosphorylation was consistently decreased by dasatinib. High-throughput kinase specificity profiling showed that AXL likely activates the SFK cluster through FAK1 which is known to complex with Src. Moreover, the SFK cluster overlapped with a previously established focal adhesion kinase (FAK1) signature conferring EMT-mediated erlotinib resistance in lung cancer cells. Finally, we show that downstream of this kinase signaling, AXL and YAP form a positive feedback loop that sustains drug tolerant persister cells. Altogether, this work demonstrates an approach for dissecting signaling regulators by which AXL drives erlotinib resistance-associated phenotypic changes. One-sentence summaryA systems biology approach elucidates the signaling pathways driving AXL-mediated erlotinib resistance in lung cancer.

cancer biology↗

bioRxiv2023

Live soil ameliorated the negative effects of biodegradable but not non-biodegradable microplastics on the growth of plant communities

O_LIPlastic pollution has become a global environmental problem. Alternative use of biodegradable plastics has been proposed to mitigate the pollution problem caused by the traditional non-biodegradable plastics but the relative impacts of both types of microplastics on plant community productivity and diversity remain unknown. Microplastics can affect growth of individual plants directly by altering plant physiological processes and indirectly by altering soil biota that in turn influence plant growth. However, it remains unknown whether soil biota can mediate impact of biodegradable and non-biodegradable microplastics on plant community productivity and diversity due to a lack of studies on the topic. C_LIO_LIHere, we performed a greenhouse experiment with six plant communities and five biodegradable and five non-biodegradable microplastics to test whether: 1) biodegradable microplastics have a less negative effect on plant community biomass production and diversity than non-biodegradable microplastics, and 2) soil microorganisms differentially mediate the effects of non-biodegradable and biodegradable microplastics on plant community biomass production and diversity. We employed a fully crossed factorial design to grow the six plant communities in the presence vs. absence of the 10 microplastics individually and in live soil vs. sterilized soil. C_LIO_LIResults show that live soil ameliorated the negative effects of biodegradable microplastics on shoot biomass of the plant communities, but microplastics suppressed plant community diversity more strongly in live soil than in sterilized soil regardless of microplastics types under averaged across all treatments. Furthermore, the specific microplastics polymers were the main drivers of these results. C_LIO_LISynthesis and applications: Overall, our findings indicate that even biodegradable microplastics, e.g. PBS, which are considered environmentally friendly, still pose significant ecological risks to the structure and productivity of plant communities with potential implications for functioning of terrestrial ecosystems. Future studies may identify the specific taxa of soil microorganisms that may have degraded the microplastics that we studied, their rates of biodegradation, and the effects thereof on plant community structure and productivity under more natural field conditions in contrasting climatic conditions. C_LI

ecology↗

bioRxiv2023

Harnessing Landrace Diversity Empowers Wheat Breeding for Climate Resilience

Breeding crops resilient to climate change is urgently needed to help ensure food security. A key challenge is to harness genetic diversity to optimise adaptation, yield, stress resilience and nutrition. We examined the genetic and phenotypic diversity of the A.E. Watkins landrace collection of bread wheat (Triticum aestivum), a major global cereal, through whole-genome re-sequencing (827 Watkins landraces and 208 modern cultivars) and in-depth field evaluation spanning a decade. We discovered that modern cultivars are derived from just two of the seven ancestral groups of wheat, leaving five groups as previously untapped sources for breeding. This provides access to landrace-specific functional variations using structured germplasm, genotyping and informatics resources. Employing complementary genetic populations and approaches, we identified thousands of high-resolution quantitative trait loci (QTL) and significant marker-trait associations for major traits, revealing many Watkins-unique loci that can confer superior traits in modern wheat. Furthermore, we identified and functionally verified causative genes for climate-change adaptation, nutritional enhancement and resistance to wheat blast. Finally, we assessed the phenotypic effects of 44,338 Watkins-unique haplotypes, introgressed from 143 prioritised QTL in the context of modern cultivars, bridging the gap between landrace diversity and current breeding. This study establishes a framework for systematically utilising genetic diversity in crop improvement to achieve sustainable food security.

plant biology↗

bioRxiv2023

Transgenic Targeting of Fcrls Creates a Highly Efficient Constitutively Active Microglia Cre Line with Differentiated Specificity

Microglia carry out important functions as the resident macrophages of the brain. To study their role in health and disease, the research community needs tools to genetically modify them with maximum completeness in a manner that distinguishes them from closely related cell-types, such as monocytes. While currently available tamoxifen-inducible CreERT2 lines are able to achieve the differentiation from other cells, the field needs improved and publicly available constitutively active Cre lines, especially ones with favorable efficiency and specificity profiles for studies where high recombination efficiency is imperative and where tamoxifen administration is contraindicated. Here, we leverage the microglia-specific Fcrls gene to generate mice expressing Cre. Using genomic methods, we show correct positioning of the transgene and intact microglia homeostasis in Fcrls-2A-Cre mice. Crossing Fcrls-2A-Cre mice to four different reporters, we demonstrate highly efficient recombination in microglia across differentially sensitive loxP alleles in different genomic contexts, indicating robust applicability of the line. Further, we show that microglia recombine a loxP reporter during early embryonic development, supporting the use of the line for developmental studies. Finally, using immunofluorescence and flow cytometry, we reveal that most border associated macrophages (BAMs) are also targeted whereas only few liver and spleen macrophages and virtually no white blood cell subsets exhibit Cre activity, distinguishing this line from another publicly available Cre line, Cx3cr1-CreM (MMRRC). Fcrls-2A-Cre mice are immediately available (JAX Stock #036591) and serve as a valuable addition to the communitys microglia toolbox by providing highly efficient constitutive Cre activity with excellent specificity, particularly for studies where tamoxifen administration is undesirable. Significance StatementThe microglia toolbox is continuously growing with more transgenic lines and most recently even viral tools becoming available. When selecting a Cre driver line, investigators must weigh relative strengths and weaknesses of available lines and carefully make the best choice for their given application. These tradeoffs include (1) availability and ease of employment, (2) chromosomal positioning of Cre with respect to the floxed allele (should not be on the same chromosome for conditional knockout studies), (3) activity level of a given Cre line and thus completeness of recombination across the microglia population, (4) specificity with respect to acceptable off-target cell types and tissues, (5) temporal aspects including earliest onset of Cre expression or inducibility, (6) robustness in disease contexts, and (7) potential perturbation of microglia homeostasis through Cre itself or disruption of the targeting locus. When selecting a mouse line, it is evident that there may not be a one-size-fits all solution but an application-based preference and choice from the diverse repertoire of microglia tools. Fcrls-2A-Cre mice are an excellent addition to this toolbox.

neuroscience↗

bioRxiv2023

The wheat powdery mildew resistance gene Pm4 also confers resistance to wheat blast

Wheat blast, caused by the fungus Magnaporthe oryzae, threatens global cereal production since its emergence in Brazil in 1985 and recently spread to Bangladesh and Zambia. Here we demonstrate that the AVR-Rmg8 effector, common in wheat-infecting isolates, is recognised by the gene Pm4, previously shown to confer resistance to specific races of Blumeria graminis f.sp. tritici, the cause of powdery mildew of wheat. We show that Pm4 alleles differ in their recognition of different AVR-Rmg8 alleles, and some confer resistance only in seedling leaves but not spikes making it important to select for those alleles that function in both tissues. This study has identified a gene recognising an important virulence factor present in wheat blast isolates in Bangladesh and Zambia and represents an important first step towards developing durably resistant wheat cultivars for these regions.

plant biology↗

bioRxiv2023

TransGeneSelector: A Transformer-based Approach Tailored for Key Gene Mining with Small Plant Transcriptomic Datasets

Gene mining, particularly from small sample sizes such as in plants, remains a challenge in life sciences. Traditional methods often omit significant genes, while deep learning techniques are hindered by small sample constraints and lack specialized gene mining approaches. This paper presents TransGeneSelector, the first deep learning method tailored for key gene mining in small transcriptomic datasets, ingeniously integrating data augmentation, sample filtering, and a Transformer-based classifier. Tested on Arabidopsis thaliana seeds germination classification using just 79 samples, it not only achieves classification performance on par with, if not superior to, Random Forest and SVM but also excels in identifying upstream regulatory genes that Random Forest might miss, and these pinpointed genes more accurately reflect the metabolic processes inherent in seed germination. TransGeneSelectors ability to mine vital genes from limited datasets signifies its potential as the current state-of-the-art in gene mining in small sample scenarios, providing an efficient and versatile solution for this critical research area.

bioinformatics↗

bioRxiv2023

Progressive community, biogeochemical and evolutionary remodeling of the soil microbiome underpins long-term desert ecosystem restoration

Ecological restoration of degraded lands is essential to human sustainability. Yet, an in-depth community, functional, and evolutionary microbial perspective of long-term restoration of damaged ecosystems is lacking. Herein, we comprehensively assessed the impact of long-term (up to 17 years) restoration of Tengger Desert, China, by multi-omic profiling of 1,910 topsoil samples. The soil biophysiochemical properties, especially soil hydraulics, microbiome stability, and functional diversity, significantly improved during restoration. The soil microbiome transitioned from an extreme oligotrophic and autotrophic community to a diverse copiotrophic ecosystem. The soil microbiota, including fungi, could mediate the soil physicochemical changes through metabolites. Importantly, the systematic rewiring of nutrient cycles featured the multi-domain preference of an efficient carbon fixation strategy in the extreme desert environment. Finally, the microbiome was evolving via positive selections of genes of biogeochemical cycles, resistance, and motility. In summary, we present a comprehensive community, functional, biogeochemical, and evolutionary landscape of the soil microbiome during the long-term restoration of desert environments. We highlight the crucial microbial role in restoration from soil hydraulic and biogeochemical perspectives, offering promising field applications. HighlightsO_LIThe desert soil microbiome transformed from simple oligotrophic to a diverse, stable, and nutrient-rich ecosystem with expanded functional diversity. C_LIO_LIRestoration led to systematically rewired biogeochemical cycles, which are highly efficient in carbon fixation in the desert environment. C_LIO_LIThe microbiome was evolving via positive selections of genes involved in biogeochemical cycles and environmental adaptations. C_LIO_LIMicrobes and metabolites could facilitate desert restoration from hydraulic and biogeochemical aspects, offering promising field applications. C_LI

microbiology↗

bioRxiv2023

SMARTdb: an integrated database for exploring single-cell multi-omics data of reproductive medicine

Single-cell multi-omics sequencing has greatly accelerated reproductive research in recent years, and the data are continually growing. However, utilizing these data resources is challenging for wet-lab researchers. A comprehensive platform for exploring single-cell multi-omics data related to reproduction is urgently needed. Here we introduce SMARTdb (single-cell multi-omics atlas of reproduction), which is an integrative and user-friendly platform for exploring molecular dynamics of reproductive development, aging, and disease, covering multi-omics, multi-species, and multi-stage data. We have curated and analyzed single-cell transcriptome and epigenome data of over 2.0 million cells from 6 species across whole lifespan. A series of powerful functionalities are provided, such as "Query gene expression", "DIY expression plot", "DNA methylation plot", and "Epigenome browser". With SMARTdb, we found that the male germ-cell-specific expression pattern of RPL39L and RPL10L is conserved between human and other model animals. Moreover, DNA hypomethylation and open chromatin may regulate the specific expression pattern of RPL39L collectively in both male and female germ cells. In summary, SMARTdb is a powerful platform for convenient data mining and gaining novel insights into reproductive development, aging, and disease. SMARTdb is publicly available at https://smart-db.cn.

genomics↗

bioRxiv2023

Septoria tritici blotch resistance gene Stb15 encodes a lectin receptor-like kinase

Septoria tritici blotch (STB), caused by the Dothideomycete fungus Zymoseptoria tritici, is of one of the most damaging diseases of bread wheat (Triticum aestivum)1 and the target of costly fungicide applications2. In line with the fungus apoplastic lifestyle, STB resistance genes isolated to date encode receptor-like kinases (RLKs) including a wall-associated kinase (Stb6) and a cysteine-rich kinase (Stb16q)3,4. Here, we used genome-wide association studies (GWAS) on a panel of 300 whole-genome shotgun-sequenced diverse wheat landraces (WatSeq consortium) to identify a 99 kb region containing six candidates for the Stb15 resistance gene. Mutagenesis and transgenesis confirmed a gene encoding an intronless G-type lectin RLK (LecRK) as Stb15. The characterisation of Stb15 exemplifies the unexpected diversity of RLKs conferring Z. tritici resistance in wheat.

genetics↗

bioRxiv2023

Epigenetic regulation of p63 blocks squamous-to-neuroendocrine transdifferentiation in esophageal development and malignancy

While cell fate determination and maintenance are important in establishing and preserving tissue identity and function during development, aberrant cell fate transition leads to cancer cell heterogeneity and resistance to treatment. Here, we report an unexpected role for the transcription factor p63 (Trp63/TP63) in the fate choice of squamous versus neuroendocrine lineage in esophageal development and malignancy. Deletion of p63 results in extensive neuroendocrine differentiation in the developing mouse esophagus and esophageal progenitors derived from human embryonic stem cells. In human esophageal neuroendocrine carcinoma (eNEC) cells, p63 is transcriptionally silenced by EZH2-mediated H3K27 trimethylation (H3K27me3). Upregulation of the major p63 isoform {Delta}Np63, through either ectopic expression or EZH2 inhibition, promotes squamous transdifferentiation of eNEC cells. Together these findings uncover p63 as a rheostat in coordinating the transition between squamous and neuroendocrine cell fates during esophageal development and tumor progression.

cell biology↗

bioRxiv2023

T2T-YAO: a Telomere-to-telomere Assembled Diploid Reference Genome for Han Chinese

Since its initial release in 2001, the human reference genome has been continuously improved in both continuity and accuracy, and the recently-released telomere-to-telomere version--T2T-CHM13--reaches its top quality after 20 years of effort. However, T2T-CHM13 does not represent an authentic diploid human genome, but rather one derived from a simplified, nearly homozygous genome of a hydatidiform mole cell line. To address this limitation and provide an alternative pertinent to the Chinese population, the largest ethnic group in the world, we have assembled a complete diploid human genome of a male Han Chinese, T2T-YAO, which includes telomere-to-telomere assemblies for all the 22+X+M and 22+Y chromosomes in his two haploids inherited separately from his parents. Both haplotypes contain no artificial sequences or model nucleotides and possess a high quality comparable to CHM13, with fewer than one error per [~]14 Mb. Derived from the individual who lives in the aboriginal region of Han Chinese, T2T-YAO shows clear ancestry and potential genetic continuity from the ancient ancestors of the Han population. Each haplotype of T2T-YAO possesses [~]340 Mb exclusive sequences and [~]3100 unique genes as compared to CHM13, and their genome sequences show greater genetic distance to CHM13 than to each other in terms of nucleotide polymorphism and structural variations. The construction of T2T-YAO would serve as a high-quality diploid reference that enables precise delineation of genomic variations in a haplotype-sensitive manner, which could advance our understandings in human evolution, hereditability of diseases and phenotypes, especially within the context of the unique variations of the Chinese population.

genetics↗

bioRxiv2023

MicroRNA-375 is induced during astrocyte-to-neuron reprogramming and promotes survival of reprogrammed neurons when overexpressed

While astrocyte-to-neuron (AtN) reprogramming holds great promise in regenerative medicine, the molecular mechanisms that govern this unique biological process remain elusive. MicroRNAs (miRNAs), as post-transcriptional regulators of gene expression, play crucial roles during development and under various pathological conditions. To understand the function of miRNAs during AtN reprogramming process, we performed RNA-seq of both mRNAs and miRNAs on human astrocyte (HA) cultures upon NeuroD1 overexpression. Bioinformatics analyses showed that NeuroD1 not only activates essential neuronal genes to initiate reprogramming process but also induces miRNA changes in HA. Among the upregulated miRNAs, we identified miR-375 and its targets, neuronal ELAVL genes (nELAVLs), which encode a family of RNA-binding proteins and are also upregulated by NeuroD1. We further showed that manipulating miR-375 level regulates nELAVLs expression during NeuroD1-mediated reprogramming. Interestingly, miR-375/nELAVLs are also induced by reprogramming factors Neurog2 and ASCL1 in HA suggesting a conserved function to neuronal reprogramming, and by NeuroD1 in the mouse astrocyte culture and spinal cord. Functionally, we showed that miR-375 overexpression improves NeuroD1-mediated reprogramming efficiency by promoting cell survival at early stages in HA even in cultures treated with the chemotherapy drug Cisplatin. Moreover, miR-375 overexpression doesnt appear to compromise maturation of the reprogrammed neurons in long term HA cultures. Lastly, overexpression of miR-375-refractory ELAVL4 induces apoptosis and reverses the cell survival-promoting effect of miR-375 during AtN reprogramming. Together, we demonstrate a neuro-protective role of miR-375 during NeuroD1-mediated AtN reprogramming and suggest a strategy of combinatory overexpression of NeuroD1 and miR-375 for improving neuronal reprogramming efficiency.

neuroscience↗

bioRxiv2023

VitTCR: A deep learning method for peptide recognition prediction

The identification of the interaction between T-cell receptors (TCRs) and immunogenic peptides is important for the development of novel cancer immunotherapies and vaccines. However, experimentally determining whether a TCR recognizes a peptide is still time- and labour-consuming. In this study, we introduced VitTCR, a predictive model based on the architecture of the vision transformer (ViT), designed to forecast TCR-peptide interactions. Prior to prediction, VitTCR converts the TCR-peptide interactions into a numerical tensor named AtchleyMaps using Atchley factors. Subsequently, VitTCR takes AtchleyMaps as inputs and predicts whether an interaction between a TCR and a peptide exists. Through comprehensive evaluations, we demonstrate that VitTCR surpasses other published methods in classifying TCR-peptide pairs, exhibiting superior performance in terms of the area under the receiver operating characteristic (AUROC) and the area under the precision-recall curve (AUPR). To determine the focal contact point between TCRs and peptides, we obtained a positional bias weight matrix (PBWM) from the empirical amino acid (AA) contact probabilities derived from 83 structurally resolved pMHC-TCR complexes. The comparison of VitTCR with and without the integration of the PBWM revealed significant enhancements in the performance of the model. Moreover, the predicted probabilities generated by VitTCR exhibit significant correlations with immunological factors such as the clonal expansion and activation percentages of T cells. This further supports the efficacy of VitTCR in capturing biologically meaningful TCR-peptide interactions. In conclusion, VitTCR provides a useful computational tool for the prediction of TCR-peptide interactions, thereby contributing to our understanding in this field.

bioinformatics↗

bioRxiv2023

Meta-omics analysis revealed structural and metabolic shifts of acidification communities after feeding with thermal hydrolysis pretreated food waste

Engineering environmental microbiomes enables carbon upcycling from organic solid waste into valuable products, such as volatile fatty acids (VFAs). This approach leverages the broad metabolic potential of natural communities to process highly heterogeneous substrates. However, solid waste conversion is often constrained by microbial hydrolysis, which limits the breakdown of particulate substrates into soluble compounds available for fermentation. Top-down engineering enhancements, such as thermal hydrolysis pretreatment (THP), can improve feedstock solubility but do not consistently increase total acid yields and may instead shift acid profiles. This highlights our limited understanding of microbiome responses to feedstock-level engineering controls. In this study, we applied genome-resolved multi-omics analysis to link VFA production performance with molecular mechanisms in a top-down engineered microbiome fed with thermally hydrolysed food waste. THP reduced total VFA yield (p = 0.003), accompanied by decreased Shannon diversity (p = 0.03), acid-production potential (DNA; log2FC = -1.3), and acid-production activity (mRNA; log2FC = -0.2). Propionate remained the dominant product with and without THP, consistent with the predominance of the Prevotella genus; however, THP selectively enriched two Prevotella species with elevated expression of ATP-generating steps in propionate production. THP also increased butyrate and valerate fractions (p < 0.001), together with upregulated reverse {beta}-oxidation for chain elongation driven by CAG-791 sp900320025 and Megasphaera sp000417505. Overall, our results provide performance- and molecular-level evidence that THP applied to complex feedstocks didnt increase total VFA yields, but reshaped microbiome structure and function, maintained propionate dominance, and promoted chain elongation.

molecular biology↗

bioRxiv2023

The Haplotype-resolved Autotetraploid Genome Assembly Provides Insights into the genomic evolution and fruit divergence in Wax apple (Syzygium samarangense (BI.) Merr.et Perry)

The wax apple (Syzygium samarangense) is an economically important fruit crop with great potential value to human health because it has rich antioxidant substances. Here, we presented one haplotype-resolved autotetraploid genome assembly of the wax apple with size of 1.59 Gb. Comparative genomic analysis revealed three rounds of whole-genome duplication (WGD) events, including two independent WGDs after WGT-{gamma}. Resequencing analysis of 35 accessions partitioned these individuals into two distinct groups, including 28 landraces and seven cultivated species, and several selectively swept genes possibly contributed to fruit growth, including KRP1-like, IAA17-like, GME-like, and FLACCA-like genes. Transcriptome analysis in three different varieties during flower and fruit development identified key genes related to fruit size, sugar content, and male sterility. We found AP2 also affects the fruit size by regulating the sepal development in wax apples. The expression of sugar transport-related genes (SWEETs and SUTs) was high in ZY, likely contributing to a high level of sugar content. Male sterility in Tub was associated with tapetal abnormalities due to the decreased expression of DYT1, TDF1, and AMS, which affects the early tapetum development. The chromosome-scale genome and large-scale transcriptome data presented in this study offer new valuable resources for biological research on S. samarangense, and sheds new light on fruit size control, sugar metabolism, and male sterility regulatory metabolism in wax apple.

genomics↗

bioRxiv2023

Latitudinal scaling of aggregation with abundance and its consequences for coexistence in species rich forests

The search for simple principles underlying the complex spatial structure and dynamics of plant communities is a long-standing challenge in ecology1-6. In particular, the relationship between the spatial distribution of plants and species coexistence is challenging to resolve in species-rich communities7-9. Analysing the spatial patterns of tree species in 21 large forest plots, we find that rare species tend to be more spatially aggregated than common species, and a latitudinal gradient in the strength of this negative correlations that increases from tropical to temperate forests. Our analysis suggests that latitudinal gradients in animal seed dispersal10 and mycorrhizal associations11,12,13 may jointly generate this intriguing pattern. To assess the consequences of negative aggregation-abundance correlations for species coexistence, we present here a framework to incorporate the observed spatial patterns into population models8 along with an analytical solution for the local extinction risk14 of species invading from low abundances in dependence of spatial structure, demographic parameters, and immigration. For example, the stabilizing effect of the observed spatial patterns reduced the local extinction risk of species when rare almost by a factor of two. Our approach opens up new avenues for integrating observed spatial patterns into mathematical theory, and our findings demonstrate that spatial patterns, such as species aggregation and segregation, can contribute substantially to coexistence in species-rich communities. This underscores the need to understand the interactions between multiple ecological processes and spatial patterns in greater detail.

ecology↗

bioRxiv2023

Deciphering the rule of antigen-antibody amino acid interaction

Antigenic drift is the biggest challenge for mutagenic RNA virus vaccine development. The most fundamental but neglected thing is to determine the immune escape mutation map (IEMM) of 20 amino acids to reveal the rule of the viral immune escape. We use universal protein tags as a linear epitope model to determine the relationship between the epitope mutation and immune escape. To describe and draw amino acid interaction maps, mutations of protein tags are classified into four types: IEM (immune escape mutation), ADERM (antibody-dependent enhancement risk mutation), EQM (equivalent mutation), and IVM (invalid mutation). To make up for the data limitation, the amino acid interaction pairs determined by 3D structure through literature search are simultaneously used to form a more systematic and universal antigen-antibody interaction maps. The results are: (i) one residue interacts with multiple amino acids in antigen-antibody interaction; (ii) Most amino acid replacements are IVM and EQM. (iii) Once aromatic amino acids replace non-aromatic amino acids, the mutation is often inactive. (iv) Substituting residues with the same physical and chemical properties easily lead to IEM. Therefore, this study had important theoretical significance for future research on antigenic drift, antibody rescue and vaccine renewal design. ImportanceWe typed the antigenic epitope mutations into IEM, ADERM, EQM, and IVM types to describe and quantify the results of antigenic mutations. According to the results, the antigen-antibody interaction rule was summarized as one-to-many interaction rule. To sum up, the Epitope mutation rules were defined as IVM and EQM predomination rule, aryl mutation escape rule and homogeneous mutation escape rule.

immunology↗