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The Farm Animal Genotype-Tissue Expression (FarmGTEx) project has been established to develop a public resource of genetic regulatory variants in livestock, which is essential for linking genetic polymorphisms to variation in phenotypes, helping fundamental biological discovery and exploitation in animal breeding and human biomedicine. Here we show results from the pilot phase of PigGTEx by processing 5,457 RNA-sequencing and 1,602 whole-genome sequencing samples passing quality control from pigs. We build a pig genotype imputation panel and associate millions of genetic variants with five types of transcriptomic phenotypes in 34 tissues. We evaluate tissue specificity of regulatory effects and elucidate molecular mechanisms of their action using multi-omics data. Leveraging this resource, we decipher regulatory mechanisms underlying 207 pig complex phenotypes and demonstrate the similarity of pigs to humans in gene expression and the genetic regulation behind complex phenotypes, supporting the importance of pigs as a human biomedical model.

Abstract Background Foot-and-mouth disease (FMD) is the most economically important and highly contagious disease of cloven-hoofed animals worldwide. Control of the disease has been mainly based on large-scale vaccinations with whole-virus inactivated vaccines. In recent years, a series of outbreaks of type O FMD occurred in China (including Chinese Taipei, Chinese Hong Kong) posed a tremendous threat to Chinese animal husbandry. Its causative agent, type O FMDV, has evolved into three topotypes (East–South Asia (ME-SA), Southeast Asia (SEA), Cathay (CHY)) in these regions, which represents an important obstacle to disease control. The available FMD vaccine in China shows generally good protection against ME-SA and SEA topotype viruses infection, but affords insufficient protection against some variants of the CHY topotype. Therefore, the choice of a new vaccine strain is of fundamental importance. Results The present study describes the generation of a full-length infectious cDNA clone of FMDV vaccine strain and a genetically modified virus with some amino acid substitutions in antigenic sites 1, 3, and 4, based on the established infectious clone. The recombinant viruses had similar growth properties to the wild O/HN/CHA/93 virus. All swine immunized with inactivated vaccine prepared from the O/HN/CHA/93 were fully protected from challenge with the viruses of ME-SA and SEA topotypes and partially protected against challenge with the virus of CHY topotype at 28 days post-immunization. In contrast, the swine inoculated with the genetically modified vaccine were completely protected from the infection of viruses of the three topotypes. Conclusions Some amino acid substitutions in the FMDV vaccine strain genome did not have an effect on the ability of viral replication in vitro. The vaccine prepared from genetically modified FMDV by reverse genetics significantly improved the protective efficacy to the variant of the CHY topotype, compared with the wild O/HN/CHA/93 virus. Thus, the full-length cDNA clone of FMDV can be a useful tool to develop genetically engineered FMDV vaccine candidates to help control porcinophilic FMD epidemics in China.

Abstract Background Ear size and shape are distinct conformation characteristics of pig breeds. Previously, we identified a significant quantitative trait locus (QTL) influencing ear surface on pig chromosome 5 in a White Duroc × Erhualian F2 resource population. This QTL explained more than 17% of the phenotypic variance. Methods Four new markers on pig chromosome 5 were genotyped across this F2 population. RT-PCR was performed to obtain expression profiles of different candidate genes in ear tissue. Standard association test, marker-assisted association test and F-drop test were applied to determine the effects of single nucleotide polymorphisms (SNP) on ear size. Three synthetic commercial lines were also used for the association test. Results We refined the QTL to an 8.7-cM interval and identified three positional candidate genes i.e. HMGA2, SOX5 and PTHLH that are expressed in ear tissue. Seven SNP within these three candidate genes were selected and genotyped in the F2 population. Of the seven SNP, HMGA2 SNP (JF748727: g.2836 A > G) showed the strongest association with ear size in the standard association test and marker-assisted association test. With the F-drop test, F value decreased by more than 97% only when the genotypes of HMGA2 g.2836 A > G were included as a fixed effect. Furthermore, the significant association between g.2836 A > G and ear size was also demonstrated in the synthetic commercial Sutai pig line. The haplotype-based association test showed that the phenotypic variance explained by HMGA2 was similar to that explained by the QTL and at a much higher level than by SOX5. More interestingly, HMGA2 is also located within the dog orthologous chromosome region, which has been shown to be associated with ear type and size. Conclusions HMGA2 was the closest gene with a potential functional effect to the QTL or marker for ear size on chromosome 5. This study will contribute to identify the causative gene and mutation underlying this QTL.

Abstract Background Elucidation of the pig transcriptome is essential for interpreting functional elements of the genome and understanding the genetic architecture of complex traits such as fat deposition, metabolism and growth. Results Here we used massive parallel high-throughput RNA sequencing to generate a high-resolution map of the porcine mRNA and miRNA transcriptome in liver, longissimus dorsi and abdominal fat from two full-sib F2 hybrid pigs with segregated phenotypes on growth, blood physiological and biochemical parameters, and fat deposition. We obtained 8,508,418-10,219,332 uniquely mapped reads that covered 78.0% of the current annotated transcripts and identified 48,045-122,931 novel transcript fragments, which constituted 17,085-29,499 novel transcriptional active regions in six tested samples. We found that about 18.8% of the annotated genes showed alternative splicing patterns, and alternative 3' splicing is the most common type of alternative splicing events in pigs. Cross-tissue comparison revealed that many transcriptional events are tissue-differential and related to important biological functions in their corresponding tissues. We also detected a total of 164 potential novel miRNAs, most of which were tissue-specifically identified. Integrated analysis of genome-wide association study and differential gene expression revealed interesting candidate genes for complex traits, such as IGF2, CYP1A1, CKM and CES1 for heart weight, hemoglobin, pork pH value and serum cholesterol, respectively. Conclusions This study provides a global view of the complexity of the pig transcriptome, and gives an extensive new knowledge about alternative splicing, gene boundaries and miRNAs in pigs. Integrated analysis of genome wide association study and differential gene expression allows us to find important candidate genes for porcine complex traits.

Abstract Background Foot-and-mouth disease virus (FMDV) uses a highly conserved Arg-Gly-Asp (RGD) triplet for attachment to host cells and this motif is believed to be essential for virus viability. Previous sequence analyses of the 1D-encoding region of an FMDV field isolate (Asia1/JS/CHA/05) and its two derivatives indicated that two viruses, which contained an Arg-Asp-Asp (RDD) or an Arg-Ser-Asp (RSD) triplet instead of the RGD integrin recognition motif, were generated serendipitously upon short-term evolution of field isolate in different biological environments. To examine the influence of single amino acid substitutions in the receptor binding site of the RDD-containing FMD viral genome on virus viability and the ability of non-RGD FMDVs to cause disease in susceptible animals, we constructed an RDD-containing FMDV full-length cDNA clone and derived mutant molecules with RGD or RSD receptor recognition motifs. Following transfection of BSR cells with the full-length genome plasmids, the genetically engineered viruses were examined for their infectious potential in cell culture and susceptible animals. Results Amino acid sequence analysis of the 1D-coding region of different derivatives derived from the Asia1/JS/CHA/05 field isolate revealed that the RDD mutants became dominant or achieved population equilibrium with coexistence of the RGD and RSD subpopulations at an early phase of type Asia1 FMDV quasispecies evolution. Furthermore, the RDD and RSD sequences remained genetically stable for at least 20 passages. Using reverse genetics, the RDD-, RSD-, and RGD-containing FMD viruses were rescued from full-length cDNA clones, and single amino acid substitution in RDD-containing FMD viral genome did not affect virus viability. The genetically engineered viruses replicated stably in BHK-21 cells and had similar growth properties to the parental virus. The RDD parental virus and two non-RGD recombinant viruses were virulent to pigs and bovines that developed typical clinical disease and viremia. Conclusions FMDV quasispecies evolving in a different biological environment gained the capability of selecting different receptor recognition site. The RDD-containing FMD viral genome can accommodate substitutions in the receptor binding site without additional changes in the capsid. The viruses expressing non-RGD receptor binding sites can replicate stably in vitro and produce typical FMD clinical disease in susceptible animals.

Abstract Background Porcine parvovirus (PPV) usually causes reproductive failure in sows. The objective of the present study was to analyze the phylogenetic distribution and perform molecular characterization of PPVs isolated in China, as well as to identify two field strains, LZ and JY. The data used in this study contained the available sequences for NS1 and VP2 from GenBank, as well as the two aforementioned Chinese strains. Results Phylogenetic analysis shows that the PPV sequences are divided into four groups. The early Chinese PPV isolates are Group I viruses, and nearly all of the later Chinese PPV isolates are Group II viruses. LZ belongs to group II, whereas the JY strain is a Group III virus. This is the first report on the isolation of a Group III virus in China. The detection of selective pressures on the PPV genome shows that the NS1 and VP2 genes are under purifying selection and positive selection, respectively. Moreover, the amino acids in the VP2 capsid are highly variable because of the positive selection. Conclusions Our study provides new molecular data on PPV strains in China, and emphasizes the importance of etiological studies of PPV in pigs.

Abstract Background Porcine reproductive and respiratory syndrome virus (PRRSV) exhibits extensive genetic variation. The outbreak of a highly pathogenic PRRS in 2006 led us to investigate the extent of PRRSV genetic diversity in China. To this end, we analyzed the Nsp2 and ORF7 gene sequences of 98 Chinese PRRSV isolates. Results Preliminary analysis indicated that highly pathogenic PRRSV strains with a 30-amino acid deletion in the Nsp2 protein are the dominant viruses circulating in China. Further analysis based on ORF7 sequences revealed that all Chinese isolates were divided into 5 subgroups, and that the highly pathogenic PRRSVs were distantly related to the MLV or CH-1R vaccine, raising doubts about the efficacy of these vaccines. The ORF7 sequence data also showed no apparent associations between geographic or temporal origin and heterogeneity of PRRSV in China. Conclusion These findings enhance our knowledge of the genetic characteristics of Chinese PRRSV isolates, and may facilitate the development of effective strategies for monitoring and controlling PRRSV in China.

Abstract Background Maternal infanticide is an extreme and failed maternal behavior, which is defined as an active attack on piglets using the jaws, resulting in serious or fatal bite wounds. It brings big economic loss to the pig industry and severe problems to piglets' welfare. But little is known about the genetic background of this behavior. Quantitative trait loci (QTL) for maternal infanticide were identified in a White Duroc × Erhualian intercross by a non-parametric linkage analysis (NPL) in our previous study. In this study, associations of 194 microsatellite markers used in NPL analysis with maternal infanticide behavior were further analyzed by transmission-disequilibrium test (TDT). On this basis, seven genes (ESR2, EAAT2, BDNF, OXTR, 5-HTR2C, DRD1 and GABRA6) at five genomic regions were selected and further analyzed. Associations of single nucleotide polymorphisms (SNPs) and haplotypes in each gene with maternal infanticide behavior were evaluated. Results Microsatellite markers on pig chromosome (SSC) 2, 13, 15, and X displayed significance at P < 0.05 by both TDT and NPL. Of the seven candidate genes, three ESR2 SNPs had nominal evidence for association (P < 0.05). Allele A at EAAT2 g. 233G > A and allele T at DRD1 g.1013C > G > T also showed evidence of overtransmission to infanticidal sows. In the overall tests of association of haplotypes, candidate genes of ESR2, EAAT2 and DRD1 achieved overall significance level (P < 0.05). Haplotype [A; A; G], [G; A; G], [A; G; G] and [C; C], respectively, from ESR2, EAAT2 and DRD1 showed higher frequencies to infanticidal sows (P < 0.05). Alleles among haplotypes and SNPs which showed an overtransmission to infanticidal sows were from White Duroc. Conclusions From association tests of SNPs and haplotypes, ESR2, EAAT2 and DRD1 showed significant associations with maternal infanticide. This result supported the existence of QTL for maternal infanticide behavior on SSC1, SSC2 and SSC16.

Abstract Background According to Office International Des Epizooties (OIE) Bulletin, the PanAsia strain of Foot-and-Mouth Disease Virus (FMDV) was invaded into the People's Republic of China in May 1999. It was confirmed that the outbreaks occurred in Tibet, Hainan and Fujian provinces. In total, 1280 susceptible animals (68 cattle, 1212 swine) were destroyed for the epidemic control. To investigate the distinct biological properties, we performed plaque assay, estimated the pathogenicity in suckling mice and determined the complete genomic sequence of FMDV swine-isolated O/Fujian/CHA/5/99 strain. In addition, a molecular modeling was carried out with the external capsid proteins. Results The pathogenicity study showed that O/Fujian/CHA/5/99 had high virulence with respect to infection in 3-day-old suckling-mice (LD50 = 10-8.3), compared to O/Tibet/CHA/1/99 (LD50 = 10-7.0) which isolated from bovine. The plaque assay was distinguishable between O/Fujian/CHA/5/99 and O/Tibet/CHA/1/99 by their plaque phenotypes. O/Fujian/CHA/5/99 formed large plaque while O/Tibet/CHA/1/99 formed small plaque. The 8,172 nucleotides (nt) of O/Fujian/CHA/5/99 was sequenced, and a phylogenetic tree was generated from the complete nucleotide sequences of VP1 compared with other FMDV reference strains. The identity data showed that O/Fujian/CHA/5/99 is closely related to O/AS/SKR/2002 (94.1% similarity). Based on multiple sequence alignments, comparison of sequences showed that the characteristic nucleotide/amino acid mutations were found in the whole genome of O/Fujian/CHA/5/99. Conclusion Our finding suggested that C275T substitution in IRES of O/Fujian/CHA/5/99 may induce the stability of domain 3 for the whole element function. The structure prediction indicated that most of 14 amino acid substitutions are fixed in the capsid of O/Fujian/CHA/5/99 around B-C loop and E-F loop of VP2 (antigenic site 2), and G-H loop of VP1 (antigenic site 1), respectively. These results implicated that these substitutions close to heparin binding sites (E136G in VP2, A174 S in VP3) and at antigenic site 1 (T142A, A152T and Q153P in VP1) may influence plaque size and the pathogenicity to suckling mice. The potential of genetic characterization would be useful for microevolution and viral pathogenesis of FMDV in the further study.

Abstract Background Analysis of DNA microarray data takes as input spot intensity measurements from scanner software and returns differential expression of genes between two conditions, together with a statistical significance assessment. This process typically consists of two steps: data normalization and identification of differentially expressed genes through statistical analysis. The Expresso microarray experiment management system implements these steps with a two-stage, log-linear ANOVA mixed model technique, tailored to individual experimental designs. The complement of tools in TM4, on the other hand, is based on a number of preset design choices that limit its flexibility. In the TM4 microarray analysis suite, normalization, filter, and analysis methods form an analysis pipeline. TM4 computes integrated intensity values (IIV) from the average intensities and spot pixel counts returned by the scanner software as input to its normalization steps. By contrast, Expresso can use either IIV data or median intensity values (MIV). Here, we compare Expresso and TM4 analysis of two experiments and assess the results against qRT-PCR data. Results The Expresso analysis using MIV data consistently identifies more genes as differentially expressed, when compared to Expresso analysis with IIV data. The typical TM4 normalization and filtering pipeline corrects systematic intensity-specific bias on a per microarray basis. Subsequent statistical analysis with Expresso or a TM4 t-test can effectively identify differentially expressed genes. The best agreement with qRT-PCR data is obtained through the use of Expresso analysis and MIV data. Conclusion The results of this research are of practical value to biologists who analyze microarray data sets. The TM4 normalization and filtering pipeline corrects microarray-specific systematic bias and complements the normalization stage in Expresso analysis. The results of Expresso using MIV data have the best agreement with qRT-PCR results. In one experiment, MIV is a better choice than IIV as input to data normalization and statistical analysis methods, as it yields as greater number of statistically significant differentially expressed genes; TM4 does not support the choice of MIV input data. Overall, the more flexible and extensive statistical models of Expresso achieve more accurate analytical results, when judged by the yardstick of qRT-PCR data, in the context of an experimental design of modest complexity.

Simple Summary: Integrating the significant loci identified from genome-wide association study (GWAS) is a strategy to improve the prediction performance of genomic selection. In this study, the significant loci identified by GWAS for carcass traits were integrated into genomic best linear unbiased prediction (GBLUP) and Bayesian genomic prediction (GP) models in different forms. The prediction accuracy, bias and running time of 15 different GP models for the number of ribs and carcass length were evaluated by 10-fold cross-validation to obtain the optimal GP model. The number of ribs (NRs) and the carcass length (CL) are important economic traits. The traits are usually measured after slaughter. To improve the prediction performance of genomic selection (GS) for NRs and CL, one strategy is to integrate the significant loci identified from whole-genome sequencing (WGS) data by genome-wide association study (GWAS) into the genomic prediction (GP) model. This study investigated the GP of different genomic best linear unbiased prediction (GBLUP) and Bayesian models using chip genotype data, imputed WGS (iWGS) data and modeling significant single-nucleotide polymorphisms (SNPs) in different ways for the GP of NRs and CL in the Suhuai pig population. The prediction accuracy, bias and running time of 15 different GP models were evaluated by 10-fold cross-validation. The prediction accuracy of GBLUP using chip data for NRs and CL was 0.314 ± 0.022 and 0.194 ± 0.040, respectively. For NRs, based on the iWGS data, treating the most significant SNP as fixed effects in the GBLUP model had the highest predictive performance, with a prediction accuracy of 0.528 ± 0.023. For CL, based on the chip data, the model that added all the significant SNPs identified by imputed data by GWAS into the multi-trait GBLUP as the second random additive effect was the highest predictive performance, with a prediction accuracy of 0.305 ± 0.027. This study provides insights into optimizing GP models for small populations with phenotypes that are difficult to measure. [ABSTRACT FROM AUTHOR]

Non-structural protein 2 (NSP2) of PRRSV is highly variable and plays crucial roles in the virus's life cycle. To elucidate the function of NSP2 during PRRSV infection, we identified SH3KBP1 as an NSP2-interacting host protein using mass spectrometry. Exogenous SH3KBP1 expression significantly inhibited PRRSV replication by enhancing IFN-I and related ISGs production. Conversely, SH3KBP1 knockdown promoted viral replication by downregulating IFN-I and ISGs levels. In vivo experiments revealed that Sh3kbp1-/- mice were more susceptible to VSV infection, exhibiting reduced serum IFN-β levels. Further investigation showed that SH3KBP1 enhances RIG-I signal transduction by increasing K63-linked polyubiquitination through interaction with the E3 ubiquitin ligase TRIM25. We also found that PRRSV infection and NSP2 overexpression induce the autophagic degradation of SH3KBP1, counteracting the host's innate immune response. A critical interaction site was identified within the third proline-rich motif in NSP2 (453PVPAPR458). Recombinant PRRSV lacking this motif displayed reduced virulence and decreased SH3KBP1 degradation. This study advances our understanding of how PRRSV interferes with the host immune response and offers valuable insights for development novel attenuated vaccines against PRRSV. Author summary: PRRS is one of the most devastating diseases affecting the global pig industry. The genome of the PRRS virus (PRRSV) exhibits high variability, characterized by rapid mutation and frequent recombination, particularly in the NSP2 gene. NSP2 plays crucial roles in viral replication, virulence, and immune regulation. This study reveals a novel strategy used by NSP2 to counteract innate immunity. We found that SH3KBP1 enhances the K63-linked polyubiquitination of RIG-I by recruiting TRIM25, thereby stabilizing RIG-I and promoting the production of IFN-I. Mice lacking SH3KBP1 were more susceptible to VSV infection and had lower survival rates. NSP2 directly binds to SH3KBP1 and induces its degradation through the autophagic pathway, aiding viral replication. Additionally, mutations in the amino acid sequences at positions 453–458 within the hypervariable domain of PRRSV NSP2 led to attenuated virulence. This research uncovers a new function for the adaptor protein SH3KBP1 and provides deeper insights into how PRRSV evades host immune responses. [ABSTRACT FROM AUTHOR]

It is a great challenge to isolate the broadly neutralizing antibodies (bnAbs) against foot-and-mouth disease virus (FMDV) due to its existence as seven distinct serotypes without cross-protection. Here, by vaccination of pig with FMDV serotype O and A whole virus antigens, we obtained 10 bnAbs against serotypes O, A and/or Asia1 by dissecting 216 common clonotypes of two serotype O and A specific porcine B-cell receptor (BCR) gene repertoires containing total 12720 B cell clones, indicating the induction of cross-serotype bnAbs after sequential vaccination with serotypes O and A antigens. The majority of porcine bnAbs (9/10) were derived from terminally differentiated B cells of different clonal lineages, which convergently targeted the conserved "RGDL" motif on structural protein VP1 of FMDV by mimicking receptor recognition to inhibit viral attachment to cells. Cryo-EM complex structures revealed that the other bnAb pOA-2 specifically targets a novel inter-pentamer antigen structure surrounding the viral three-fold axis, with a highly conserved determinant at residue 68 on VP2. This unique binding pattern enabled cross-serotype neutralization by destabilizing the viral particle. The evolutionary analysis of pOA-2 demonstrated its origin from an intermediate B-cell, emphasizing the crucial role of somatic hypermutations (SHMs) in balancing the breadth and potency of neutralization. However, excessive SHMs may deviate from the trajectory of broad neutralization. This study provides a strategy to uncover bnAbs against highly mutable pathogens and the cross-serotype antigenic structures to explore broadly protective FMDV vaccine. Author summary: The scarcity of broadly neutralizing antibodies (bnAbs) in the body significantly hinders their discovery and elucidation of the conserved antigenic structure of highly mutable pathogens. Foot-and-mouth disease virus (FMDV) severely infects pigs and exists as seven distinct serotypes without cross-protection. In this study, we present a strategy for rapid discovery of cross-serotype bnAbs by constructing of specific B-cell repertoires and exploring of common clonotypes. We originally isolated porcine bnAbs against FMDV serotypes O, A and/or Asia1, and proved for the first time that receptor binding region in VP1 can induce the production of cross-serotype bnAbs. The evolution of cross-serotype bnAbs reveals how somatic hypermutations balance the breadth and potency of neutralization. FMDV bnAbs employ dual neutralization mechanisms to neutralize viruses via receptor mimicry and destabilizing the viral particles. This study provides valuable guidelines that facilitate the isolation of bnAbs against the highly variable viruses and aid in designing a universal FMDV vaccine. [ABSTRACT FROM AUTHOR]

Over the past few decades, significant improvements in maize yield have been largely attributed to increased plant density of upright hybrid varieties rather than increased yield per plant. However, dense planting triggers shade avoidance responses (SARs) that optimize light absorption but impair plant vigor and performance, limiting yield improvement through increasing plant density. In this study, we demonstrated that high-density-induced leaf angle narrowing and stem/stalk elongation are largely dependent on phytochrome B (phyB1/B2), the primary photoreceptor responsible for perceiving red (R) and far-red (FR) light in maize. We found that maize phyB physically interacts with the LIGULELESS1 (LG1), a classical key regulator of leaf angle, to coordinately regulate plant architecture and density tolerance. The abundance of LG1 is significantly increased by phyB under high R:FR light (low density) but rapidly decreases under low R:FR light (high density), correlating with variations in leaf angle and plant height under various densities. In addition, we identified the homeobox transcription factor HB53 as a target co-repressed by both phyB and LG1 but rapidly induced by canopy shade. Genetic and cellular analyses showed that HB53 regulates plant architecture by controlling the elongation and division of ligular adaxial and abaxial cells. Taken together, these findings uncover the phyB-LG1- HB53 regulatory module as a key molecular mechanism governing plant architecture and density tolerance, providing potential genetic targets for breeding maize hybrid varieties suitable for high-density planting. This study uncovers a phyB-centered regulatory module in maize that maintains plant performance under high R:FR light (low density) conditions and ensures their survival under low R:FR light (high density) conditions. These findings offer potential targets for breeding maize hybrid varieties with enhanced density tolerance and suitable for high-density planting. [ABSTRACT FROM AUTHOR]

This article proposes a low cross-axis sensitivity resonant MEMS(Micro-Electro-Mechanical Systems) accelerometer that is optimized based on the BP and NSGA-II algorithms. When resonant accelerometers are used in seismic monitoring, automotive safety systems, and navigation applications, high immunity and low cross-axis sensitivity are required. To improve the high immunity of the accelerometer, a coupling structure is introduced. This structure effectively separates the symmetric and antisymmetric mode frequencies of the DETF resonator and prevents mode coupling. To obtain higher detection accuracy and low cross-axis sensitivity, a decoupling structure is introduced. To find the optimal dimensional parameters of the decoupled structure, the BP and NSGA-II algorithms are used to optimize the dimensional parameters of the decoupled structure. The optimized decoupled structure has an axial stiffness of 6032.21 N/m and a transverse stiffness of 6.29 N/m. The finite element analysis results show that the sensitivity of the accelerometer is 59.1 Hz/g (Y-axis) and 59 Hz/g (X-axis). Cross-axis sensitivity is 0.508% (Y-axis) and 0.339% (X-axis), which is significantly lower than most resonant accelerometers. The coupling structure and optimization method proposed in this paper provide a new solution for designing resonant accelerometers with high interference immunity and low cross-axis sensitivity. [ABSTRACT FROM AUTHOR]