Biology subjects

Guo, Z.

Publications and source records attributed to Guo, Z..

At least 145 records · Page 8Linked to original sources

bioRxiv2023

magpie: a power evaluation method for differential RNA methylation analysis in N6-methyladenosine sequencing

MotivationRecently, novel biotechnologies to quantify RNA modifications became an increasingly popular choice for researchers who study epitran-scriptome. When studying RNA methylations such as N6-methyladenosine (m6A), researchers need to make several decisions in its experimental design, especially the sample size and a proper statistical power. Due to the complexity and high-throughput nature of m6A sequencing measurements, methods for power calculation and study design are still currently unavailable. ResultsWe propose a statistical power assessment tool, magpie, for power calculation and experimental design for epitranscriptome studies using m6A sequencing data. Our simulation-based power assessment tool will borrow information from real pilot data, and inspect various influential factors including sample size, sequencing depth, effect size, and basal expression ranges. We integrate two modules in magpie: (i) a flexible and realistic simulator module to synthesize m6A sequencing data based on real data; and (ii) a power assessment module to examine a set of comprehensive evaluation metrics. AvailabilityThe proposed power assessment tool magpie is publicly available as a R/Bioconductor package at: https://bioconductor.org/packages/magpie/.

bioinformatics↗

bioRxiv2023

Pan-cancer characterization and clinical outcome of ecDNA-enhancer mediated transcriptional dysregulation

Extrachromosomal circular DNAs (ecDNAs) are extrachromosomal circular DNA elements harboring enhancers that can function as mobile transcriptional enhancers to promote oncogene amplification in diverse human cancers. However, little is known about the mechanism how ecDNA and relevant enhancers influence the transcription control in different cancers. Here, we performed a comprehensive pan-cancer analysis to explore the potential transcriptional regulatory network between ecDNA and enhancer, and the association with clinical outcomes in different human cancers. Firstly, we identified 18,385 enhancers on ecDNA in 1,921 samples of 20 TCGA tumors. By integrating corresponding RNA-seq data, we found that the expression levels of enhancer RNAs (eRNAs) were significantly different between ecDNA regions and corresponding linear chromosomes. This suggested that enhancers on ecDNA may employ eRNA to perform transcriptional regulation. Furthermore, we identified enhancer co-amplification with oncogenes and found that enhancers on ecDNA significantly affect the expression of co-amplified cancer genes and consequently influence the survival of cancer patients. In addition, we found that, compared to corresponding linear chromosomes, enhancers on ecDNA generally have lower levels of methylation, which may be mainly caused by the enhancer co-amplification with oncogenes. Genome-wide analysis of open chromatin regions revealed significantly higher levels of chromatin accessibility and certain chromosomal preferences in ecDNA regions comparing corresponding linear chromosomes. Moreover, we found that the downregulation of antigen presentation genes and the suppression of antigen presentation pathways may cause the tumor immune evasion mediated by ecDNA. Finally, we identified tumor-infiltrating activated mast cells in ecDNA-positive patients, which are associated with poorer prognosis. In summary, through pan-cancer analysis, we illustrate the characteristics and regulatory mechanisms of ecDNA and its enhancers in cancers, providing insights for future cancer treatment.

bioinformatics↗

bioRxiv2023

Transmissibility, infectivity, and immune resistance of the SARS-CoV-2 BA.2.86 variant

In September 2023, the SARS-CoV-2 XBB descendants, such as XBB.1.5 and EG.5.1 (originally XBB.1.9.2.5.1), are predominantly circulating worldwide. Unexpectedly, however, a lineage distinct from XBB was identified and named BA.2.86 on August 14, 2023. Notably, BA.2.86 bears more than 30 mutations in the spike (S) protein when compared to XBB and the parental BA.2, and many of them are assumed to be associated with immune evasion. Although the number of reported cases is low (68 sequences have been reported as of 7 September 2023), BA.2.86 has been detected in several continents (Europe, North America and Africa), suggesting that this variant may be spreading silently worldwide. On 17 August 2023, the WHO designated BA.2.86 as a variant under monitoring. Here we show evidence suggesting that BA.2.86 potentially has greater fitness than current circulating XBB variants including EG.5.1. The pseudovirus assay showed that the infectivity of BA.2.86 was significantly lower than that of B.1.1 and EG.5.1, suggesting that the increased fitness of BA.2.86 is not due to the increased infectivity. We then performed a neutralization assay using XBB breakthrough infection sera to address whether BA.2.86 evades the antiviral effect of the humoral immunity induced by XBB subvariants. The 50% neutralization titer of XBB BTI sera against BA.2.86 was significantly (1.6-fold) lower than those against EG.5.1. The sera obtained from individuals vaccinated with 3rd-dose monovalent, 4th-dose monovalent, BA.1 bivalent, and BA.5 bivalent mRNA vaccines exhibited very little or no antiviral effects against BA.2.86. Moreover, the three monoclonal antibodies (Bebtelovimab, Sotrovimab and Cilgavimab), which worked against the parental BA.2, did not exhibit antiviral effects against BA.2.86. These results suggest that BA.2.86 is one of the most highly immune evasive variants ever.

microbiology↗

bioRxiv2023

ReDis: efficient metagenomic profiling via assigning ambiguous reads

SummaryMetagenomic profiling is one of the primary means of microbiome analysis, which includes classification of sequencing reads and quantification of their relative abundances. Although mang methods have been developed for metagenomic profiling, metagenomic profiling remains challenges on striking a delicate balance between accuracy and runtime as well as assigning the ambiguous reads. Here, we present a novel method, named ReDis, to overcome the above issues. ReDis combines Kraken2 with Minimap2 for aligning sequencing reads against a reference database with hundreds of gigabytes (GB) in size accurately within feasible time, and then uses a novel statistical model to assign the ambiguous reads for producing accurate abundance estimates. In contrast to the popular Kraken2+Bracken, ReDis improved the accuracy of abundance estimation on simulated reads from two highly similar genomes: Escherichia coli and Shigella flexneri. Contacth.guo@foxmail.com or jlsljf0101@126.com

bioinformatics↗

bioRxiv2023

Antibody inhibition of influenza A virus assembly and release

Antibodies are frontline defenders against influenza virus infection, providing protection through multiple complementary mechanisms. Although a subset of monoclonal antibodies (mAbs) have been shown to restrict replication at the level of virus assembly and release, it remains unclear how potent and pervasive this mechanism of protection is, due in part to the challenge of separating this effect from other aspects of antibody function. To address this question, we developed imaging-based assays to determine how effectively a broad range of mAbs against the IAV surface proteins can specifically restrict viral egress. We find that classically neutralizing antibodies against hemagglutinin are broadly multifunctional, inhibiting virus assembly and release at concentrations one- to twenty-fold higher than the concentrations at which they inhibit viral entry. These antibodies are also capable of altering the morphological features of shed virions, reducing the proportion of filamentous particles. We find that antibodies against neuraminidase and M2 also restrict viral egress, and that inhibition by anti-neuraminidase mAbs is only partly attributable to a loss in enzymatic activity. In all cases, antigen crosslinking - either on the surface of the infected cell, between the viral and cell membrane, or both - plays a critical role in inhibition, and we are able to distinguish between these modes experimentally and through a structure-based computational model. Together, these results provide a framework for dissecting antibody multifunctionality that could help guide the development of improved therapeutic antibodies or vaccines, and that can be extended to other viral families and antibody isotypes.

microbiology↗

bioRxiv2023

A Plant Flavonol Rescues a Pathogenic Mutation Associated with Kinesin in Neurons

KIF1A, a microtubule-based motor protein responsible for axonal transport, is linked to a group of neurological disorders known as KIF1A-associated neurological disorder (KAND). Current therapeutic options for KAND are limited. Here, we introduced the clinically relevant KIF1A(R11Q) variant into the C. elegans homolog UNC-104, resulting in uncoordinated animal behaviors. Through genetic suppressor screens, we identified intragenic mutations in UNC-104s motor domain that rescued synaptic vesicle localization and coordinated movement. We showed that two suppressor mutations partially recovered motor activity in vitro by counteracting the structural defect caused by R11Q at KIF1As nucleotide-binding pocket. We found that supplementation with fisetin, a plant flavonol, improved KIF1A(R11Q) worms movement and morphology. Notably, our biochemical and single-molecule assays revealed that fisetin directly restored the ATPase activity and processive movement of human KIF1A(R11Q) without affecting wild-type KIF1A. These findings suggest fisetin as a potential intervention for enhancing KIF1A(R11Q) activity and alleviating associated defects in KAND.

cell biology↗

bioRxiv2023

High red/far-red ratio promotes root colonization of Serratia plymuthica A21-4 in tomato by root exudates-stimulated chemotaxis and biofilm formation

Effective colonization on plant roots is a prerequisite for plant growth promoting rhizobacterias (PGPR) to exert beneficial activities. Light is essential for plant growth, development and stress response. However, how light modulates root colonization of PGPR remains unclear. Here, we found that high red/far red(R/FR) light promoted and low R/FR light inhibited the colonization and growth enhancement of Serratia plymuthica A21-4 on tomato. Non-targeted metabolomic analysis of root exudates collected from different R/FR ratio treated tomato seedlings with A21-4 inoculation by ultra performance liquid chromatography-tandem mass spectrometry showed that 64 primary metabolites including amino acids, sugars and organic acids in high R/FR light-grown plants significantly increased compared with those determined for low R/FR light-grown plants. Among them, 7 amino acids, 1 organic acid and 1 sugar obviously induced the chemotaxis and biofilm formation of A21-4 compared to the control. Furthermore, exogenous addition of five artificial root exudate compontents (leucine, methionine, glutamine, 6-aminocaproic acid and melezitose) regained and further increased the colonization and growth promoting ability of A21-4 in tomato under low R/FR light and high R/FR light, respectively, indicating their involvement in high R/FR light-regulated the interaction of tomato root and A21-4. Taken together, our results, for the first time, clearly demonstrate that high R/FR light-induced root exudates play a key role in chemotaxis, biofilm formation and root colonization of A21-4. This study provides new insights into the interactions of plant-PGPR under different light conditions and can help promote the combined application of light supplementation and PGPR to facilitate crop growth and health in green agricultural production.

microbiology↗

bioRxiv2023

Variations in Homoeologous Dosage and Epigenomics Mark the Early Evolution of Synthetic Brassica Tetraploids

Polyploidization is important in plant evolution and is becoming increasingly important in crop breeding and material creation. Studies have provided evidence for structural variations and epigenomic repatterning in synthetic polyploidizations, but the relationships between structural and epigenomic variations, as well as their effects on gene expression and phenotypic variations are unknown. Here, we investigated the genome-wide large deletion/duplication regions (DelDups) and genomic methylation dynamics, in the leaf organ as a representative, of progenies from eight generations that derived from the synthetic tetraploidization between Brassica rapa and Brassica oleracea. We found that half or complete deletion/duplication of fragments ranging in size from 400 kb to 65.85 Mb, with a mean size of 5.70 Mb, occurred frequently from the first generation of selfing and thereafter. The genes located in these DelDups expressed at levels expected for a positive dosage effect, as indicated by the positive association between expression and the copy number of these genes. Plants containing these DelDups also showed distinct phenotypic variations. The whole genome methylation level experienced significant fluctuations in different generations and eventually decreased in the latter generations. Moreover, the DelDups did not show methylation changes from other individuals of the same generation, and the local regions with methylation alterations did not affect gene expression. Our findings provide new insights into the early evolution of polyploid genomes and guide the use of synthetic polyploidizations in breeding.

genomics↗

bioRxiv2023

Insights from the Early Cretaceous: The promise of Lycoptera aDNA sequencing

Obtaining high-quality ancient DNA (aDNA) is a crucial process for advancements in molecular paleontology. However, current research is restricted to a limited range of fossil types due to DNA degradation and contamination from environmental DNA (eDNA). Utilizing the technology of nanoparticle affinity beads, we successfully extracted DNA from Lycoptera davidi fossils and obtained 1,258,901 DNA sequences. To ascertain their origins, we developed and implemented a novel protocol, the "mega screen method", designed to categorize aDNA fragments. This approach successfully identified 243 Actinopterygii species-specific fragments (SSFs), which subsequent analysis confirmed as original in situ DNA (oriDNA) sequences. Lycoptera davidi, a ray-finned fish from the Early Cretaceous Jehol Biota, dates back approximately 120 million years (Ma). Notably, the absence of deamination in certain oriDNA and paleoenvironmental DNA (paeDNA) fragments calls into question its reliability as a definitive marker for aDNA identification, a phenomenon potentially attributable to the protective effects of fossil diagenesis. Additionally, we identified a novel mechanism, "coding region sliding replication and recombination", responsible for generating new transposase. This mechanism, distinct from conventional processes such as horizontal gene transfer or vertical inheritance from parents, can facilitate a rapid genomic diversification. The transposase CDS insertion into the GAS2 gene of Anabarilius grahami offers molecular insights into the genetic interactions between ancestral carp and Lycoptera and the swift emergence of the expansion of early fish species starting from the early Cretaceous. These findings enhance our understanding of fossil DNA preservation, lay the groundwork for an ancient species DNA database, and introduce innovative tools for exploring evolutionary relationships across geological timescales.

paleontology↗

bioRxiv2023

Targeted Protein O-GlcNAcylation Using Bifunctional Small Molecules

Protein O-linked {beta}-N-acetylglucosamine modification (O-GlcNAcylation) plays a crucial role in regulating essential cellular processes. The disruption of O-GlcNAcylation homeostasis has been linked to various human diseases, including cancer, diabetes, and neurodegeneration. However, there are limited chemical tools for protein- and site-specific O-GlcNAc modification, rendering the precise study of O-GlcNAcylation challenging. To address this, we have developed first-in-class heterobifunctional small molecules, named O-GlcNAcylation targeting chimeras (OGTACs), which enable protein-specific O-GlcNAcylation in cells. OGTACs promote O-GlcNAcylation of proteins such as BRD4, CK2, and EZH2 in cellulo by recruiting O-GlcNAc transferase (OGT), with temporal and magnitude control. Mass spectrometry data revealed that OGTACs induced site-selective O-GlcNAcylation of BRD4. Overall, OGTACs represent a promising approach for inducing protein-specific O-GlcNAcylation, thus enabling functional dissection and offering new directions for O-GlcNAc-targeting therapeutic development.

cell biology↗

bioRxiv2023

Genetically Encodable in situ Gelation Redox-Responsive Collagen-Like Protein Hydrogel for Accelerating Diabetic Wound Healing

Genetically encoded collagen-like protein-based hydrogels have demonstrated remarkable efficacy in promoting the healing process in diabetic patients. However, the current methods for preparing these hydrogels pose significant challenges due to harsh reaction conditions and the reliance on chemical crosslinkers. In this study, we present a genetically encoded approach that allows for the creation of protein hydrogels without the need for chemical additives. Our design involves the genetic encoding of paired-cysteine residues at the C- and N-terminals of a meticulously engineered collagen-like recombination protein. The protein-based hydrogel undergoes a gel-sol transition in response to redox stimulation, achieving a sol-gel transition. We provide evidence that the co-incubation of the protein hydrogel with 3T3 cells not only enhances cell viability but also promotes cell migration. Moreover, the application of the protein hydrogel significantly accelerates the healing of diabetic wounds by upregulating the expression of COL-1 and CK-14, while simultaneously reducing oxidant stress in the wound microenvironment. Our study highlights a straightforward and chemical-free strategy for the preparation of redox-responsive protein hydrogels. Importantly, our findings underscore the potential of this hydrogel system for effectively treating diabetic wounds, offering a promising avenue for future therapeutic applications.

bioengineering↗

bioRxiv2023

Seasonal Variation in Bacterial Community Structures of Mangrove Sediments

Climate change globally and sea level rise affect the mangrove ecosystem. The high diversity and temporal heterogeneity of the mangrove ecosystem will lead to a high diversity of sediment bacterial community structure and function. However, seasonal variations and potential assembly mechanisms of sediment bacterial communities in mangrove ecosystems remain to be discovered. We collected rhizosphere sediments and bulk sediments from Kandelia obovata and Aegiceras corniculatum at three locations covering Dongzhai Harbour in spring, summer, autumn, and winter, and sequenced 16S rRNAs. The results indicated that the alpha and beta diversity of bacterial communities in mangrove sediments differed significantly between seasons, and the bacterial communities in rhizosphere sediments had smaller seasonal changes and were more stable than those in bulk sediment bacterial communities. The seasonal changes in carbon, nitrogen content, and pH were the main influencing factors. The stochastic process dominated the assembly of bacterial communities in mangrove sediments. The assembly of bacterial communities varies between seasons. We found that the proportion of dispersal limitation was significantly negatively correlated with the carbon and nitrogen content in the sediment. Compared with bulk components, the dispersal limitation of bacterial communities in rhizosphere sediments accounted for a lower proportion of community construction, which might be caused by higher carbon and nitrogen content conditions in rhizosphere sediments. We found that beta diversity based on Bray-Curtis distance was significantly positively correlated with dispersal limitation, which explained why the beta diversity of bacterial communities in rhizosphere sediments was significantly lower than that of bulk components. This study increases the understanding of the responses of mangrove bacterial communities to seasonal change and may be beneficial for the protection of mangrove ecosystems in the face of climate change.

ecology↗

bioRxiv2023

Enhancing AlphaFold-Multimer-based Protein Complex Structure Prediction with MULTICOM in CASP15

AlphaFold-Multimer has emerged as the state-of-the-art tool for predicting the quaternary structure of protein complexes (assemblies or multimers) since its release in 2021. To further enhance the AlphaFold-Multimer-based complex structure prediction, we developed a new quaternary structure prediction system (MULTICOM) to improve the input fed to AlphaFold-Multimer and evaluate and refine the outputs generated by AlphaFold2-Multimer. Specifically, MULTICOM samples diverse multiple sequence alignments (MSAs) and templates for AlphaFold-Multimer to generate structural models by using both traditional sequence alignments and new Foldseek-based structure alignments, ranks structural models through multiple complementary metrics, and refines the structural models via a Foldseek structure alignment-based refinement method. The MULTICOM system with different implementations was blindly tested in the assembly structure prediction in the 15th Critical Assessment of Techniques for Protein Structure Prediction (CASP15) in 2022 as both server and human predictors. Our server (MULTICOM_qa) ranked 3rd among 26 CASP15 server predictors and our human predictor (MULTICOM_human) ranked 7th among 87 CASP15 server and human predictors. The average TM-score of the first models predicted by MULTICOM_qa for CASP15 assembly targets is [~]0.76, 5.3% higher than [~]0.72 of the standard AlphaFold-Multimer. The average TM-score of the best of top 5 models predicted by MULTICOM_qa is [~]0.80, about 8% higher than [~]0.74 of the standard AlphaFold-Multimer. Moreover, the novel Foldseek Structure Alignment-based Model Generation (FSAMG) method based on AlphaFold-Multimer outperforms the widely used sequence alignment-based model generation. The source code of MULTICOM is available at: https://github.com/BioinfoMachineLearning/MULTICOM3.

bioinformatics↗

bioRxiv2023

ImSpiRE: Image feature-aided spatial resolution enhancement method

The resolution of most spatially resolved transcriptomic technologies usually cannot attain the single-cell level, limiting their applications in biological discoveries. Here, we introduce ImSpiRE, an image feature-aided spatial resolution enhancement method for in situ capturing spatial transcriptome. Taking the information stored in histological images, ImSpiRE solves an optimal transport problem to redistribute the expression profiles of spots to construct new transcriptional profiles with enhanced resolution, together with imputing the gene expression profiles in unmeasured regions. Applications to multiple datasets confirm that ImSpiRE can enhance spatial resolution to the subspot level while contributing to the discovery of tissue domains, signaling communication patterns, and spatiotemporal characterization.

bioinformatics↗

bioRxiv2023

Improving AlphaFold2-based Protein Tertiary Structure Prediction with MULTICOM in CASP15

Since CASP14, AlphaFold2 has become the standard method for protein tertiary structure prediction. One remaining challenge in the field is to further improve the accuracy of AlphaFold2-based protein structure prediction. To address this challenge, we developed a new version of the MULTICOM system to sample diverse multiple sequence alignments (MSAs) and structural templates to improve the input for AlphaFold2 to generate structural models. The models are then ranked by both the pairwise model similarity and AlphaFold2 self-reported model quality score. The top ranked models are further refined by a novel structure alignment-based refinement method powered by Foldseek. Moreover, for a monomer target that is a subunit of a protein assembly (complex), MULTICOM integrates tertiary and quaternary structure prediction together to account for tertiary structural changes induced by protein-protein interaction in the assembly. The MULTICOM system participated in the tertiary structure prediction in the 15th Critical Assessment of Techniques for Protein Structure Prediction (CASP15) in 2022 as server and human predictors. Our best server predictor (MULTICOM_refine) ranked 3rd among 47 CASP15 server predictors and our best human predictor (MULTICOM) ranked 7th among all 132 human and server predictors. The average GDT-TS score and TM-score of the first structural models that MULTICOM_refine predicted for 94 CASP15 domains are [~]0.80 and [~]0.92, 9.6% and 8.2% and higher than [~]0.73 and 0.85 of the standard AlphaFold2 predictor respectively. The results demonstrate that our approach can significantly improve the accuracy of the AlphaFold2-based protein tertiary structure prediction. The source code of MULTICOM is available at: https://github.com/BioinfoMachineLearning/MULTICOM3.

bioinformatics↗

bioRxiv2023

Active Transcription and Epigenetic Reactions Synergistically RegulateMeso-Scale Genomic Organization

In interphase nuclei, chromatin is organized into interspersed dense domains with characteristic sizes, both in the nuclear interior and periphery. However, the quantitative impact of transcription and histone modifications on the size and distribution of these domains remains unclear. Here, we introduce a mesoscale theoretical model that investigates the relationship between heterochromatic domain sizes and loop extrusion rates from these domains. The model considers chromatin-chromatin and chromatin-lamina interactions, methylation and acetylation kinetics, and diffusion of epigenetic marks and nucleoplasm. Our model generates testable predictions that help reveal the biophysics underlying chromatin organization in the presence of transcription-driven loop extrusion. This process is kinetically captured through the conversion of heterochromatin to euchromatin in response to RNAPII activity. We discovered that a balance between diffusive and reactive fluxes governs the steady-state sizes of heterochromatin domains. Using theory and simulations, we predicted that a loss of transcription results in increased chromatin compaction and larger heterochromatin domain sizes. To validate our predictions, we employed complementary super-resolution and nano-imaging techniques on five different cell lines with impaired transcription. We quantitatively assessed how domain sizes scale with loop extrusion rates at the hetero-euchromatin interfaces. Our analysis of previously obtained super-resolution images of nuclei revealed that excessive loop extrusion leads to smaller heterochromatin domains. The model successfully recapitulated these observations, explaining how transcription loss can counteract the effects of cohesin overloading. As the general biophysical mechanisms regulating heterochromatin domain sizes are independent of cell type, our findings have significant implications for understanding the role of transcription in global genome organization.

biophysics↗

bioRxiv2023

Neural dynamics in the limbic system during male social behaviors

Sexual and aggressive behaviors are two evolutionarily conserved social behaviors vital for an animals survival and reproductive success. While an increasing number of brain regions in the limbic system have been identified as functionally relevant for these two types of behaviors, an understanding of how social cues are represented across brain regions and how social behaviors are generated via this network activity remains elusive. To gain a holistic view of the neural responses during social behaviors, we utilized multi-fiber photometry to simultaneously record Ca2+ signals of estrogen receptor alpha (Esr1)-expressing cells from 13 limbic brain regions in male mice during sexual and aggressive behaviors and compare the response magnitude and temporal patterns across regions. We find that conspecific sensory information, as well as social action initiation signals, are widely distributed in the limbic system and can be decoded from the network activity. Cross-region correlation analysis reveals striking increases in functional connectivity in the network during the action initiation phase of social behaviors whereas advanced copulation is accompanied by a "dissociated" network state. Based on the response patterns, we propose a mating-biased network (MBN) and an aggression-biased network (ABN) for mediating male sexual and aggressive behaviors, respectively.

neuroscience↗

bioRxiv2023

Combining pairwise structural similarity and deep learning interface contact prediction to estimate protein complex model accuracy in CASP15

Estimating the accuracy of quaternary structural models of protein complexes and assemblies (EMA) is important for predicting quaternary structures and applying them to studying protein function and interaction. The pairwise similarity between structural models is proven useful for estimating the quality of protein tertiary structural models, but it has been rarely applied to predicting the quality of quaternary structural models. Moreover, the pairwise similarity approach often fails when many structural models are of low quality and similar to each other. To address the gap, we developed a hybrid method (MULTICOM_qa) combining a pairwise similarity score (PSS) and an interface contact probability score (ICPS) based on the deep learning inter-chain contact prediction for estimating protein complex model accuracy. It blindly participated in the 15th Critical Assessment of Techniques for Protein Structure Prediction (CASP15) in 2022 and ranked first out of 24 predictors in estimating the global accuracy of assembly models. The average per-target correlation coefficient between the model quality scores predicted by MULTICOM_qa and the true quality scores of the models of CASP15 assembly targets is 0.66. The average per-target ranking loss in using the predicted quality scores to rank the models is 0.14. It was able to select good models for most targets. Moreover, several key factors (i.e., target difficulty, model sampling difficulty, skewness of model quality, and similarity between good/bad models) for EMA are identified and analayzed. The results demonstrate that combining the multi-model method (PSS) with the complementary single-model method (ICPS) is a promising approach to EMA. The source code of MULTICOM_qa is available at https://github.com/BioinfoMachineLearning/MULTICOM_qa.

bioinformatics↗