Biology subjects

Li, Q.

Publications and source records attributed to Li, Q..

At least 325 records · Page 18Linked to original sources

bioRxiv2024

Mutation of phosphatidate phosphohydrolase genes confers broad-spectrum disease resistance in plants

Phosphatidic acid (PA) is considered as a second messenger that interacts with protein kinases, phosphatases and NADPH oxidases, amplifying the signal to initiate plant defense signaling responses (Li and Wang, 2019). In rice, mutation of RBL1 causes the accumulation of PA, enhancing multipathogen resistance (Sha et al., 2023). In our previous study, we attempted to rescue rbl1 mutant by overexpressing phosphatidate phosphohydrolase (PAH) genes. However, overexpression of PAH2 reduced the PA level but did not affect the disease resistance, which made us to reconsider the importance of PA and PAH in rice immunity. Here, we identified that mutation of PAHs caused PA accumulation and enhanced multipathogen resistance in rice and Arabidopsis.

plant biology↗

bioRxiv2024

NSP4 mutation T492I drives rapid evolution of SARS-CoV-2 toward Omicron

T492I, a mutation encountered in SARS-CoV-2 nonstructural protein 4 (NSP4), enhances viral replication and alters nonstructural protein cleavage, causing potential evolutionary impacts. Through comprehensive comparative analyses based on evolve-and-resequence experiments of SARS-CoV-2 wild-type and Delta strains with or without T492I, we demonstrate that NSP4 T492I not only increases the mutation rate, but also accelerates the emergence of many mutations characteristic for Omicron variants. Accordingly, viral populations that evolved from ancestors with T492I, show Omicron-biased selective forces and increases in viral replication, infectivity, immune evasion capacity, potentials for cross-species transmission and receptor-binding affinity. Aside from enhanced replication, we observed stronger epistasis regarding viral replication and infectivity in T492I than in S N501Y and NSP6 {Delta}SGF; this facilitates the regulation of mutation types, which can drive fast evolution of Omicron specific mutations. Our results highlight the role of an important replication-enhancing mutation in regulating the evolutionary rates and mutational trends of SARS-CoV-2.

evolutionary biology↗

bioRxiv2024

Integrated Analysis of Single-Cell and Bulk RNA-Seq Data reveals that Ferroptosis-Related Genes Mediated the Tumor Microenvironment predicts Prognosis, and guides Drug Selection in Triple-Negative Breast Cancer

BackgroundTriple-negative breast cancer (TNBC) is aggressive, lacking methods to predict recurrence and drug sensitivity. Ferroptotic heterogeneity varies in TNBC subtypes. However, the tumor microenvironment (TME) mediated by ferroptosis genes is unclear. Our study aims to integrate single-cell and bulk RNA sequencing (RNA-seq) data to reveal the ferroptosis-mediated TME in TNBC, predicting prognosis and guiding treatment. MethodsThe single-cell and bulk RNA-seq data of TNBC were sourced from the Gene Expression Omnibus (GEO) database. Using these data, a machine learning algorithm was employed to integrate and analyze the characteristics of the TME mediated by ferroptosis-related genes in TNBC. Prediction models for TNBC survival prognosis and drug treatment response were established and then validated in an independent set. ResultsAt the individual cell level, T cells were categorized into three distinct subpopulations, and local macrophages into two subpopulations. The infiltration degree of these different cell subpopulations was closely associated with prognosis and treatment outcomes. Based on this, the risk score model we developed effectively predicted recurrence-free survival in TNBC patients, with independently validated pooled predicted 3-, 4-, and 5-year Area Under the Curves (AUCs) of 0.65, 0.67, and 0.71, respectively. Additionally, we found that patients in the high-risk group may be more responsive to 27 drugs. ConclusionsWe have uncovered the tumor immune cell clusters in TNBC mediated by ferroptosis. A risk score model was constructed to identify high-risk TNBC patients, which can assist physicians in disease monitoring and precision therapy. The genes identified hold significant potential as therapeutic targets for TNBC patients. FundingThis project is funded by the National Natural Science Foundation of China (81974268, 82472000, 82304151), the Talent Incentive Program of Cancer Hospital Chinese, Academy of Medical Sciences (801032247), the Cooperation Fund of CHCAMS (CFA202202023), and the open project of Beijing Key Laboratory of Tumor Invasion and Metastasis Mechanism, Capital Medical University(2023ZLKF03). Impact StatementIntegrating single-cell and bulk RNA-seq data elucidates the role of ferroptosis in TNBC, offering a prognostic model and personalized therapeutic insights.

cancer biology↗

bioRxiv2024

Structure-Mechanics Principles and Mechanobiology of Fibrocartilage Pericellular Matrix: A Pivotal Role of Type V Collagen

The pericellular matrix (PCM) is the immediate microniche surrounding resident cells in various tissue types, regulating matrix turnover, cell-matrix cross-talk and disease initiation. This study elucidated the structure-mechanical properties and mechanobiological functions of the PCM in fibrocartilage, a family of connective tissues that sustain complex tensile and compressive loads in vivo. Studying the murine meniscus as the model tissue, we showed that fibrocartilage PCM contains thinner, random collagen fibrillar networks that entrap proteoglycans, a structure distinct from the densely packed, highly aligned collagen fibers in the bulk extracellular matrix (ECM). In comparison to the ECM, the PCM has a lower modulus and greater isotropy, but similar relative viscoelastic properties. In Col5a1+/D menisci, the reduction of collagen V, a minor collagen localized in the PCM, resulted in aberrant fibril thickening with increased heterogeneity. Consequently, the PCM exhibited a reduced modulus, loss of isotropy and faster viscoelastic relaxation. This disrupted PCM contributes to perturbed mechanotransduction of resident meniscal cells, as illustrated by reduced intracellular calcium signaling, as well as upregulated biosynthesis of lysyl oxidase and tenascin C. When cultured in vitro, Col5a1+/D meniscal cells synthesized a weakened nascent PCM, which had inferior properties towards protecting resident cells against applied tensile stretch. These findings underscore the PCM as a distinctive microstructure that governs fibrocartilage mechanobiology, and highlight the pivotal role of collagen V in PCM function. Targeting the PCM or its molecular constituents holds promise for enhancing not only meniscus regeneration and osteoarthritis intervention, but also addressing diseases across various fibrocartilaginous tissues.

bioengineering↗

bioRxiv2024

Fibrillarin modulates fetal hemoglobin silencing

Decoding the molecular mechanisms underlying human fetal ({gamma}) globin gene silencing impacts therapeutic strategies for {beta}-thalassemia and sickle cell disease. Here, we identified a nucleolar protein, fibrillarin (FBL), which mediates the methylation of glutamine104 in histone H2A and functions as a repressor of the {gamma}-globin gene in cultured erythroid cells, including those from {beta}-thalassemia patients. Conditional Fbl depletion in adult {beta}-YAC transgenic mice or in {beta}IVS-2-654-thalassemic mice reactivated the human {gamma}-globin gene or murine embryonic globin expression, respectively, which corrects hematologic and pathologic defects in {beta}-thalassemic mice. We showed that FBL plays a dual role in activating BCL11A expression and repressing {gamma}-globin gene expression, which is dependent on its histone methyltransferase activity. Our study may provide an alternative strategy for therapeutic targeted treatment of {beta}-hemoglobinopathies.

molecular biology↗

bioRxiv2024

ACE-2 Blockade & TMPRSS2 Inhibition Mitigate SARS-CoV-2 Severity Following Cigarette Smoke Exposure in Airway Epithelial Cells In Vitro

Cigarette smoking is associated with COVID-19 prevalence and severity, but the mechanistic basis for how smoking alters SARS-CoV-2 pathogenesis is unknown. A potential explanation is that smoking alters the expression of the SARS-CoV-2 cellular receptor and point of entry, angiotensin converting enzyme-2 (ACE-2), and its cofactors including transmembrane protease serine 2 (TMPRSS2). We investigated the impact of cigarette smoking on the expression of ACE-2, TMPRSS2, and other known cofactors of SARS-CoV-2 infection and the resultant effects on infection severity in vitro. Cigarette smoke extract (CSE) exposure increased ACE-2 and TMPRSS2 mRNA expression compared to air control in ferret airway cells, Calu-3 cells, and primary human bronchial epithelial (HBE) cells derived from normal and COPD donors. CSE-exposed ferret airway cells inoculated with SARS-CoV-2 had a significantly higher intracellular viral load versus vehicle-exposed cells. Likewise, CSE-exposure increased both SARS-CoV-2 intracellular viral load and viral replication in both normal and COPD HBE cells over vehicle control. Apoptosis was increased in CSE-exposed, SARS-CoV-2-infected HBE cells. Knockdown of ACE-2 via an antisense oligonucleotide (ASO) reduced SARS-CoV-2 viral load and infection in CSE-exposed ferret airway cells that was augmented by co-administration of camostat mesylate to block TMPRSS2 activity. Smoking increases SARS-CoV-2 infection via upregulation of ACE2 and TMPRSS2.

cell biology↗

bioRxiv2024

Loss of cell junctional components and matrix alterations drive cell desquamation and fibrotic changes in Idiopathic Pulmonary Fibrosis

The distal bronchioles in Idiopathic Pulmonary Fibrosis (IPF) exhibit histopathological abnormalities such as bronchiolization, peribronchiolar fibrosis and honeycomb cysts that contribute to the overall architectural remodeling of lung tissue seen in the disease. Here we describe an additional histopathologic finding of epithelial desquamation in patients with IPF, wherein epithelial cells detach from the basement membrane of the distal bronchioles. To understand the mechanism driving this pathology, we performed spatial transcriptomics of the epithelial cells and spatial proteomics of the basement membrane of the distal bronchioles from IPF patients and patients with no prior history of lung disease. Our findings reveal a downregulation of cell junctional components, upregulation of epithelial-mesenchymal transition signatures and dysregulated basement membrane matrix in IPF distal bronchioles, facilitating epithelial desquamation. Further, functional assays identified regulation between Collagen IV in the matrix, and the junctional genes JUP and PLEC, that is crucial for maintaining distal bronchiolar homeostasis. In IPF, this balanced regulation between matrix and cell-junctions is disrupted, leading to loss of epithelial adhesion, peribronchiolar fibrosis and epithelial desquamation. Overall, our study suggests that in IPF the interplay between the loss of cell junctions and a dysregulated matrix results in desquamation of distal bronchiolar epithelium and lung remodeling, exacerbating the disease. One Sentence SummaryTwo-way regulation of cell junctional proteins and matrix proteins drives cellular desquamation and fibrosis in the distal bronchioles of patients with Idiopathic Pulmonary Fibrosis.

pathology↗

bioRxiv2024

RSG-YOLO: Detection of rice seed germination rate based on enhanced YOLOv8 and multi-scale attention feature fusion

The lack of obvious difference between germinated seeds and non-germinated seeds will cause the low accuracy of detecting rice seed germination rate, remains a challenging issue in the field. In view of this, a new model named Rice Seed Germination-YOLO (RSG-YOLO) is proposed in this paper. This model initially incorporates CSPDenseNet to streamline computational processes while preserving accuracy. Furthermore, the BRA, a dynamic and sparse attention mechanism is integrated to highlight critical features while minimizing redundancy. The third advancement is the employment of a structured feature fusion network, based on GFPN, aiming to reconfigure the original Neck component of YOLOv8, thus enabling efficient feature fusion across varying levels. An additional detection head is introduced, improving detection performance through the integration of variable anchor box scales and the optimization of regression losses. This paper also explores the influence of various attention mechanisms, feature fusion techniques, and detection head architectures on the precision of rice seed germination rate detection. Experimental results indicate that RSG-YOLO achieves a mAP50 of 0.981, marking a 4% enhancement over the mAP50 of YOLOv8 and setting a new benchmark on the RiceSeedGermination dataset for the detection of rice seed germination rate.

plant biology↗

bioRxiv2024

Design of linear and cyclic peptide binders of different lengths only from a protein target sequence

Structure prediction technology has revolutionised the field of protein design, but key questions such as how to design new functions remain. Many proteins exert their functions through interactions with other proteins, and a significant challenge is designing these interactions effectively. While most efforts have focused on larger, more stable proteins, shorter peptides offer advantages such as lower manufacturing costs, reduced steric hindrance, and the ability to traverse cell membranes when cyclized. However, less structural data is available for peptides and their flexibility makes them harder to design. Here, we present a method to design both novel linear and cyclic peptide binders of varying lengths based solely on a protein target sequence. Our approach does not specify a binding site or the length of the binder, making the procedure completely blind. We demonstrate that linear and cyclic peptide binders of different lengths can be designed with nM affinity in a single shot, and adversarial designs can be avoided through orthogonal in silico evaluation, tripling the success rate. Our protocol, EvoBind2 is freely available https://github.com/patrickbryant1/EvoBind.

bioinformatics↗

bioRxiv2024

The up-regulation of TGF-beta1 by miRNA-132-3p/WT1 is involved in inducing leukemia cells to differentiate into macrophages

Although it has been shown that abnormal expression of Wilms tumor gene 1 (WT1) is associated with the occurrence of leukemia, the specific mechanism via which it induces leukemia cells to differentiate into macrophages remains poorly understood. Based on the prediction that the microRNA miRNA-132-3p is the miRNA that possibly lies upstream of the WT1 gene, we hypothesized that miRNA-132-3p may participate in the polarization process of macrophages through regulating expression of the WT1 gene. The focus of the present study was therefore to investigate the role of the miRNA-132-3p/WT1 signaling axis in the differentiation of THP-1 leukemia cells into macrophages induced by PMA. The results obtained indicated that, compared with the control group, the proliferation of THP-1 cells was clearly inhibited by PMA, and the cell cycle was arrested at G0/G1 phase, associated with an upregulation of CD11b and CD14 expression. Induced by PMA, the expression level of miRNA-132-3p was increased, WT1 expression was decreased, and the expression level of TGF-{beta}1 was increased. Following transfection with miRNA-132-3p mimics, however, the expression of WT1 in the THP-1 cells was downregulated, with upregulation of the CD11b and CD14 antigens, whereas this downregulation of WT1 mediated by miRNA-132-3p mimics could be reversed by co-transfection with WT1 vector, which was accompanied by downregulation of the CD11b and CD14 antigens. The luciferase activity of the co-transfected miRNA-132-3p mimic + WT1-wild-type (WT) group was found to be statistically significantly lower compared with that of the co-transfected miRNA-132-3p mimic + WT1-mutated (MUT) group. Furthermore, chromatin immunoprecipitation experiments showed that WT1 was able to directly target the promoter of the downstream target gene TGF-{beta}1, which led to the negative modulation of TGF-{beta}1 expression, whereas downregulation of WT1 led to an upregulation of the expression of TGF-{beta}1, which thereby promoted the differentiation of THP-1 cells into macrophages. Taken together, the present study has provided evidence, to the best of the authors knowledge for the first time, that the miRNA-132-3p/WT1/TGF-{beta}1 axis is able to regulate the committed differentiation of leukemia cells into macrophages.

immunology↗

bioRxiv2024

Inhibitor of cardiolipin biosynthesis-related enzyme MoGep4 confers broad-spectrum anti-fungal activity

Plant pathogens cause devastating diseases, leading to serious losses to agriculture. Mechanistic understanding of pathogenesis of plant pathogens lays the foundation for the development of fungicides for disease control. Mitophagy, a specific form of autophagy, is important for fungal virulence. The role of cardiolipin, mitochondrial signature phospholipid, in mitophagy and pathogenesis is largely unknown in plant pathogenic fungi. The functions of enzymes involved in cardiolipin biosynthesis and relevant inhibitors were assessed using a set of assays, including genetic deletion, plant infection, lipidomics, chemical-protein interaction, chemical inhibition, and field trials. Our results showed that the cardiolipin biosynthesis-related gene MoGEP4 of the rice blast fungus Magnaporthe oryzae regulates growth, conidiation, cardiolipin biosynthesis, and virulence. Mechanistically, MoGep4 regulated mitophagy and Mps1-MAPK phosphorylation, which are required for virulence. Chemical alexidine dihydrochloride (AXD) inhibited the enzyme activity of MoGep4, cardiolipin biosynthesis and mitophagy. Importantly, AXD efficiently inhibited the growth of 10 plant pathogens and controlled rice blast and Fusarium head blight in the field. Our study demonstrated that MoGep4 regulates mitophagy, Mps1 phosphorylation and pathogenesis in M. oryzae. In addition, we found that the MoGep4 inhibitor, AXD, displays broad-spectrum antifungal activity and is a promising candidate for fungicide development.

microbiology↗

bioRxiv2024

The continuous differentiation of multiscale structural gradients from childhood to adolescence correlates with the maturation of cortical morphology and functional specialization

From childhood to adolescence, the structural organization of the human brain undergoes dynamic and regionally heterogeneous changes across multiple scales, from synaptic pruning to the reorganization of large-scale anatomical wiring. However, during this period, the developmental process of multiscale structural architecture, its association with cortical morphological changes, and its role in the maturation of functional organization remain largely unknown. Here, we utilized a longitudinal multimodal imaging dataset including 276 children aged 6 to 14 years to investigate the developmental process of multiscale cortical wiring. We used an in vivo model of cortical wiring that combines features of white matter tractography, cortico-cortical proximity, and microstructural similarity to construct a multiscale brain structural connectome. By employing the gradient mapping method, the gradient space derived from the multiscale structural connectome effectively recapitulated the sensory-association axis and anterior-posterior axis. Our findings revealed a continuous expansion of the multiscale structural gradient space during development, with the principal gradient increasingly distinguishing between primary and transmodal regions. This age-related differentiation coincided with regionally heterogeneous changes in cortical morphology. Furthermore, our study revealed that developmental changes in coupling between multiscale structural and functional connectivity were correlated with functional specialization refinement, as evidenced by changes in the participation coefficient. We also found that the differentiation of the principal multiscale structural gradient was associated with improved cognitive abilities, such as enhanced working memory and attention performance, and potentially supported by molecular processes related to synaptic functions. These findings advance our understanding of the intricate maturation process of brain structural organization and its implications for cognitive performance.

neuroscience↗

bioRxiv2024

B4 Raf-like MAPKKK RAF24 regulates Arabidopsis thaliana flowering time through HISTONE MONO-UBIQUITINATION 2

The timing of flowering is a critical agronomic trait governed by a number of external cues. Despite our genetic understanding of flowering time being well established, we have a limited understanding of how these signals are transmitted to different flowering genes through protein phosphorylation. Here, we characterize a novel B4 Raf-like MAPKKK protein kinase called RAF24, whose mutation results in an early flowering phenotype. Comparative analysis to related B4 Raf-like MAPKKKs indicates that RAF24 uniquely affects flowering time, while phosphoproteome analyses found RAF24 impacts the phosphorylation status of proteins involved in distinct flowering pathways. In particular, we found the RING-type ubiquitin ligase HISTONE MONO-UBIQUITINATION 2 (HUB2) to possess the largest phosphorylation change in raf24 deficient plants relative to wild-type Arabidopsis and that RAF24 suppresses ligase activity of HUB2 in order to maintain appropriate levels of H2Bub1. Furthermore, we found that RAF24 regulates HUB2 phosphorylation through subclass I and III SUCROSE NON-FERMENTING KINASE 2 (SnRK2) protein kinases; known substrates of B4 RAF-like MAPKKKs. Lastly, using a combination of phospho-mimetic and -ablative plant lines, we validate the importance of HUB2 phosphorylation at S314 in regulating flowering time. Collectively, our findings implicate RAF24 as a higher-order flowering regulator, while further implicating HUB2 as a centerpiece of flowering regulation.

plant biology↗

bioRxiv2024

CLCC1 Governs Bilayer Equilibration at the Endoplasmic Reticulum to Maintain Cellular and Systemic Lipid Homeostasis

The intricate orchestration of lipid production, storage, and mobilization is vital for cellular and systemic homeostasis1,2. Dysfunctional plasma lipid control represents the major risk factor for cardio-metabolic diseases, the leading cause of human mortality3,4. Within the cellular landscape, the endoplasmic reticulum (ER) is the central hub of lipid synthesis and secretion, particularly in metabolically active hepatocytes in the liver or enterocytes in the gut5,6. Initially assembled in the ER lumen, lipid-ferrying lipoproteins necessitate the cross-membrane transfer of both neutral and phospho-lipids onto the lumenal apolipoprotein B (APOB), in a poorly-defined process7-10. Here we show that trans-bilayer equilibration of phospholipids, regulated by the ER protein CLCC1, determines lipid partition across the ER membrane and consequently systemic lipid homeostasis. CLCC1 partners with the phospholipid scramblase TMEM41B11,12 to recognize imbalanced bilayers and promote lipid scrambling, thereby licensing lipoprotein biogenesis and the subsequent bulk lipid transport. Strikingly, loss of CLCC1 or TMEM41B leads to the emergence of giant lumenal lipid droplets enclosed by extensively imbalanced ER bilayers, and consequently drastically accelerated pathogenesis of metabolic-dysfunction-associated liver steatohepatitis (MASH). The above results establish phospholipid scrambling at the ER as the lynchpin to maintain a dynamic equilibrium. Considering the requirement of trans-bilayer phospholipid equilibration in numerous biological processes, ranging from catabolic autophagy to viral infection13-16, our study may enable further elucidation of a previously under-appreciated homeostatic control mechanism intrinsic to the ER function in lipid biogenesis and distribution.

cell biology↗

bioRxiv2024

Pulmonary Fibrosis Ferret Model Demonstrates Sustained Fibrosis, Restrictive Physiology, and Aberrant Repair

RationaleThe role of MUC5B mucin expression in IPF pathogenesis is unknown. Bleomycin-exposed rodent models do not exhibit sustained fibrosis or airway remodeling. Unlike mice, ferrets have human-like distribution of MUC5B expressing cell types and natively express the risk-conferring variant that induces high MUC5B expression in humans. We hypothesized that ferrets would consequently exhibit aberrant repair to propagate fibrosis similar to human IPF. MethodsBleomycin (5U/kg) or saline-control was micro-sprayed intratracheally then wild-type ferrets were evaluated through 22 wks. Clinical phenotype was assessed with lung function. Fibrosis was assessed with {micro}CT imaging and comparative histology with Ashcroft scoring. Airway remodeling was assessed with histology and quantitative immunofluorescence. ResultsBleomycin ferrets exhibited sustained restrictive physiology including decreased inspiratory capacity, decreased compliance, and shifted Pressure-Volume loops through 22 wks. Volumetric {micro}CT analysis revealed increased opacification of the lung bleomycin-ferrets. Histology showed extensive fibrotic injury that matured over time and MUC5B-positive cystic structures in the distal lung suggestive of honeycombing. Bleomycin ferrets had increased proportion of small airways that were double-positive for CCSP and alpha-tubulin compared to controls, indicating an aberrant proximalization repair phenotype. Notably, this aberrant repair was associated with extent of fibrotic injury at the airway level. ConclusionsBleomycin-exposed ferrets exhibit sustained fibrosis through 22 wks and have pathologic features of IPF not found in rodents. Ferrets exhibited proximalization of the distal airways and other pathologic features characteristic of human IPF. MUC5B expression through native cell types may play a key role in promoting airway remodeling and lung injury in IPF.

physiology↗

bioRxiv2024

A Regularized Bayesian Dirichlet-multinomial Regression Model for Integrating Single-cell-level Omics and Patient-level Clinical Study Data

SummaryThe abundance of various cell types can vary significantly among patients with varying phenotypes and even those with the same phenotype. Recent scientific advancements provide mounting evidence that other clinical variables, such as age, gender, and lifestyle habits, can also influence the abundance of certain cell types. However, current methods for integrating single-cell-level omics data with clinical variables are inadequate. In this study, we propose a regularized Bayesian Dirichlet-multinomial regression framework to investigate the relationship between single-cell RNA sequencing data and patient-level clinical data. Additionally, the model employs a novel hierarchical tree structure to identify such relationships at different cell-type levels. Our model successfully uncovers significant associations between specific cell types and clinical variables across three distinct diseases: pulmonary fibrosis, COVID-19, and non-small cell lung cancer. This integrative analysis provides biological insights and could potentially inform clinical interventions for various diseases.

bioinformatics↗

bioRxiv2024

GCRTcall: a Transformer based basecaller for nanopore RNA sequencing enhanced by gated convolution and relative position embedding via joint loss training

Nanopore sequencing, renowned for its ability to sequence DNA and RNA directly with read lengths extending to several hundred kilobases or even megabases, holds significant promise in fields like transcriptomics and other omics studies. Despite its potential, the technologys limited accuracy in base identification has restricted its widespread application. Although many algorithms have been developed to improve DNA decoding, advancements in RNA sequencing remain limited. Addressing this challenge, we introduce GCRTcall, a novel approach integrating Transformer architecture with gated convolutional networks and relative positional encoding for RNA sequencing signal decoding. Our evaluation demonstrates that GCRTcall achieves state-of-the-art performance in RNA basecalling.

bioinformatics↗

bioRxiv2024

BaseNet: A Transformer-Based Toolkit for Nanopore Sequencing Signal Decoding

Nanopore sequencing provides a rapid, convenient and high-throughput solution for nucleic acid sequencing. Accurate basecalling in nanopore sequencing is crucial for downstream analysis. Traditional approaches such as Hidden Markov Models (HMM), Recurrent Neural Networks (RNN), and Convolutional Neural Networks (CNN) have improved basecalling accuracy but there is a continuous need for higher accuracy and reliability. In this study, we introduce BaseNet, an open-source toolkit that utilizes transformer models for advanced signal decoding in nanopore sequencing. BaseNet incorporates both autoregressive and non-autoregressive transformer-based decoding mechanisms, offering state-of-the-art algorithms freely accessible for future improvement. Our research indicates that cross-attention weights effectively map the relationship between current signals and base sequences, joint loss training through adding a pair of forward and reverse decoder facilitate model converge, and large-scale pre-trained models achieve superior decoding accuracy. This study helps to advance the field of nanopore sequencing signal decoding, contributes to technological advancements, and provides novel concepts and tools for researchers and practitioners.

bioinformatics↗