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Liang, C.

Publications and source records attributed to Liang, C..

At least 55 records · Page 3Linked to original sources

Promotion of new expression of connexin gene Cx46 (GJA3) in the cochlea after Cx26 (GJB2) deficiency

Connexin 26 (Cx26, GJB2) mutations induce a high incidence of hearing loss, responsible for 70-80% of nonsyndromic hearing loss. The pathological changes mainly locate in the cochlea. However, the genetic changes in the cochlea after deficiency of Cx26 remail unclear, which hampers to fully understand the underlying deafness mechanisms to develop therapeutic interventions. In this study, we employed bulk Poly(A) RNA-Seq technique and found that Cx26 deficiency could cause many genes up-regulating and down-regulating in the cochlea. A significant change was that Cx46 (GJA3), which is like Cx26 but expresses in the eye rather than the ear normally, had a remarkable upregulation and occurred in the cochlea after Cx26 deficiency. Immunofluorescent staining confirmed that Cx46 had expression in the cochlea and integrated into the gap junction networks among the cochlear supporting cells and in the cochlear lateral wall at the same location as Cx26 expression. Moreover, newly expressed Cx46 could be found in the same gap junctional plaques with Cx26. In addition, this promotion of new Cx46 expression is Cx26-specific; there was no promotion of Cx46 expression in the cochlea after deletion of Cx30 (GJB6), which also predominantly co-expresses with Cx26 in the cochlea. These data demonstrated that Cx26 deficiency could promote Cx26-like Cx46 expression in the cochlea for compensation. This finding also provides a new cue for developing a genetic approach to treat this common hereditary deafness induced by GJB2 mutations. HighlightO_LINew Cx46 compensatively expresses in the cochlea after Cx26 deficiency C_LIO_LICx46 expression occurs in the same location as Cx26 in the cochlea C_LIO_LICx46 promotion is Cx26-specific, no expression in the Cx30 KO cochlea C_LI

genetics↗

A Cancer-Specific Antigen Drives Histone Acetylation by Stabilizing the Acetyltransferases

Histone acetylation is a critical epigenetic modification that regulates gene expression by modulating chromatin structure and function. Histone acetyltransferases are essential for maintaining acetylation homeostasis and the disruption of this balance can lead to aberrant gene expression and cancer development. Here, we describe that the cancer-specific protein MAGE-A10 increases cellular histone acetylation by stabilizing essential histone acetyltransferases KAT2A and KAT2B. The aberrant expression of MAGE-A10 in tumors prevents the degradation of KAT2A/2B through p62-mediated autophagy. Mechanistically, MAGE-A10 antagonizes the binding of KAT2A/2B with the E3 ubiquitin ligase complex CUL4A-DDB1, thereby decreasing the formation of their K63-linked ubiquitination. Furthermore, KAT2A enhances the transcription of the MAGE-A10 gene, forming a positive feedback loop that contributes to tumorigenesis. These findings provide insights into the molecular mechanisms hijacked in cancer that drive perturbed histone acetylation and suggest potential therapeutic strategies.

cancer biology↗

scWGBS-GPT: A Foundation Model for Capturing Long-Range CpG Dependencies in Single-Cell Whole-Genome Bisulfite Sequencing to Enhance Epigenetic Analysis

Single-cell DNA methylomes are challenging to interpret because of sparse CpG coverage and the complexity of genome-wide sequences. We present scDNAm-GPT, a universal foundation model that uses context-aware CpG tokenization, a Mamba backbone, and cross-attention to capture both local and global DNA methylation patterns. Trained on over one million single cells from 35 human and mouse tissues, scDNAm-GPT enables accurate cell clustering, zero-shot prediction of CpG effects on gene expression, improved trajectory inference, and reference-free deconvolution of cell types from cell-free DNA. The model hierarchically learns regulatory features, and its attention maps highlight functionally relevant regions, demonstrating high biological interpretability. These results establish scDNAm-GPT as a scalable and generalizable framework for single-cell epigenomic analysis, offering new opportunities to dissect epigenetic regulation in health and disease. Code is available at GitHub (https://github.com/ChaoqiLiang/scDNAm-GPT).

bioinformatics↗

Smoke exposure triggers rapid transcriptional changes and reveals glycosyltransferases linked to smoke taint in ripening grape berries

With the increasing frequency of wildfires, vineyards are more often exposed to smoke, resulting in a higher risk of smoke taint in wine. This taint imparts undesirable "smoky" and "ashy" aromas and causes significant economic losses. Smoke-derived volatile phenols (VPs) in grape berries, metabolized into stable, non-volatile glycoconjugates via glycosyltransferases (GTs), underlie smoke taint formation. Here, we present the dwarf grapevine cultivar Pixie as a model system for smoke taint research. We generated a phased, telomere-to-telomere diploid genome using HiFi long-read sequencing, along with an expression atlas spanning 30 replicated samples across various tissues and developmental stages. We also constructed a second telomere-to-telomere assembly for Pinot Noir to assess GT expression during berry ripening in the field. Controlled smoke-exposure experiments profiled GT expression and enabled transcriptome-wide analyses at multiple time points. We measured VPs in both smoke-exposed and control samples, revealing 12 GT1 genes significantly upregulated by smoke, named Vitis vinifera smoke-inducible UGTs (VviSIUGTs). Their expression peaked one day post-exposure and declined by day three, mirroring glycoside accumulation dynamics. Gene co-expression network analyses highlighted stress-responsive modules enriched in these VviSIUGTs, while transcription factor binding site analyses pinpointed stress-related regulatory elements in their promoters. These findings provide new insights into the molecular basis of smoke taint and identify potential targets for breeding and biotechnological interventions aimed at developing grapevine cultivars with reduced susceptibility to smoke damage.

plant biology↗

LCORL and STC2 variants increase body size and growth rate in cattle and other animals

Using ancestral recombination graphs, we investigated recent selection signatures in European beef cattle breeds, pinpointing sweep-driving variants in the LCORL and STC2 loci with notable effects on body size and growth rate. The ACT-to-A frameshift mutation in LCORL occurs mainly in central-European cattle, and stimulates growth. Remarkably, convergent truncating mutations were also found in commercial breeds of sheep, goats, pigs, horses, dogs, rabbits, and chickens. In the STC2 gene, we identified a missense mutation (A60P) located within the conserved region across vertebrates. We validated the two natural mutations in gene-edited mouse models, where both variants in homozygous carriers increase the average weight by 11%. Our findings provide insights into a seemingly recurring gene target of body size enhancing truncating mutations across domesticated species, and offer valuable targets for gene editing-based breeding in animals.

genetics↗

Crosslinker-free in situ hydrogel induces self-aggregation of human dental pulp stem cells with enhanced antibacterial activity

Recently, injectable hydrogels have garnered significant attention in tissue engineering due to their controlled flowability, strong plasticity, adaptability, and good biocompatibility. However, research on readily injectable in situ-forming hydrogels capable of forming functional three-dimensional (3D) tissue condensations remains limited. This study explores the development and evaluation of a carboxymethyl chitosan (CMCTS) / oxidized hyaluronic acid (oHA) hydrogel incorporated with silver sulfadiazine (AgSD) for tissue engineering applications with inherent antibacterial activity. Through physicochemical analysis, the optimal formulation of CMCTS/oHA hydrogels was established. The hydrogel demonstrated excellent injectability, enabling minimally invasive in situ delivery. In vitro cytotoxicity assays identified 0.1% AgSD as the optimal concentration, supporting cell proliferation while exhibiting antimicrobial efficacy against S. mutans and E. faecalis. In vivo studies revealed complete hydrogel degradation and good biocompatibility, with no adverse tissue reactions. The hydrogels ability to form 3D cell aggregates and support tissue regeneration underscores its potential for future 3D tissue engineering applications. Consequently, the injectable CMCTS/oHA/AgSD hydrogel developed in this study holds significant potential for application in a wide range of bioengineering fields, including antibacterial substance delivery systems and 3D tissue engineering, indicating potential for future clinical application.

bioengineering↗

CLCNet: a contrastive learning and chromosome-aware network for genomic prediction in plants

Genomic selection (GS) leverages genome-wide markers and phenotypes to predict breeding values, with its effectiveness largely dependent on the accuracy of genomic prediction (GP) models. However, GP methods often struggle to capture inter-individual variability and are limited by the curse of dimensionality, where the number of SNPs far exceeds the sample size. To address these challenges, we present CLCNet (Contrastive Learning and Chromosome-aware Network), a novel deep learning framework that integrates contrastive learning and chromosome-aware feature modeling. CLCNet comprises two key components: (i) a contrastive learning module that enhances the models ability to capture fine-grained, genotype-dependent phenotypic differences among individuals, and (ii) a chromosome-aware module that captures structured feature selection at both chromosome and genome levels, thereby distilling the most informative SNPs. We evaluated CLCNet across four crop species, covering ten agronomically important traits, and compared it with a diverse set of classical linear, machine learning, and deep learning models. CLCNet achieved superior prediction performance, with statistically significant improvements in Pearson correlation coefficient (PCC), ranging from 0.34% to 12.19% over baseline, together with reduced mean squared error (MSE). Performance gains were more pronounced for traits with moderate linkage disequilibrium (LD; r2 = 0.21-0.36) and high heritability (h2 > 0.66), such as those in maize, rapeseed, and soybean. For cotton traits characterized by high LD (r2 = 0.74) and lower heritability (h2 < 0.50), CLCNet maintained robust performance without degradation. Overall, these results demonstrate that CLCNet is an effective framework for improving genomic prediction accuracy and holds strong potential for practical applications in plant breeding. Short abstractCLCNet is a novel deep learning framework for genomic prediction that integrates contrastive learning with chromosome-aware feature selection. By jointly modeling inter-individual genotype-phenotype variation and chromosomal genomic structure, CLCNet improves prediction accuracy under high-dimensional, low-sample-size conditions. Across four crop species and ten agronomic traits, CLCNet consistently outperformed classical statistical, machine learning, and existing deep learning models. The framework also identified biologically relevant SNPs and candidate genes, demonstrating its potential for practical applications in genomic selection and computational plant breeding. Key pointsO_LIWe propose CLCNet, a multi-task deep learning framework that integrates contrastive learning with chromosome-aware feature selection for genomic prediction, under high-dimensional, low-sample-size conditions. C_LIO_LIThe chromosome-aware module explicitly exploits genomic structural information to select representative and informative SNPs across chromosomes. C_LIO_LIContrastive learning improves model robustness by stabilizing representation learning and reducing the influence of random effects across samples. C_LIO_LIBy complementing GWAS analyses, CLCNet provides additional insights into genotype-phenotype relationships with potential relevance for gene discovery. C_LI Biographical NoteJiangwei Huang is a PhD candidate at the Institute of Genetics and Developmental Biology, Chinese Academy of Sciences. His research focuses on genomic prediction, deep learning, and computational plant breeding. Zhihan Yang is a PhD candidate at the Institute of Genetics and Developmental Biology, Chinese Academy of Sciences. Her research interests include genomic prediction and bioinformatics. Rongcheng Han is an associate professor at the Institute of Genetics and Developmental Biology, Chinese Academy of Sciences. His research focuses on bioinformatics and plant phenomics. Yuqiang Jiang is a professor at the Institute of Genetics and Developmental Biology, Chinese Academy of Sciences. His research interests include plant genomics, plant phenomics and genetic improvement. Organization descriptionThe Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, is a leading research institute focusing on genetics, genomics, molecular breeding, bioinformatics, and systems biology in plants and animals.

genomics↗

Homogeneously crosslinked in situ hydrogel enclosing high-density human-cancer cells promotes vascularized in vivo tumor modeling for immune cell therapy

Cancer models in animal studies play a central role in cancer research, particularly in investigating vascularized tumor tissues for the validation of immune cell therapies. However, xenografts relying solely on cancer cells are ineffective for optimal tumor tissue formation. Additionally, tumor modeling using hydrogels with cancer cells to promote vascularization often leaves behind residual biomaterials that inhibit integration with surrounding tissues. To address these issues, we utilized a straightforward in vivo vascularized tumor modeling method with a completely degradable, crosslinker-free carboxymethyl chitosan (CMCTS)/oxidized hyaluronic acid (OHA) hydrogel that encapsulates high-density human cancer cells for in situ injection. The CMCTS/oHA hydrogel was fully degraded within 3 weeks, enabling three-dimensional (3D) cell condensation in vitro. 2 weeks after subcutaneous injection in mice, solid tumors formed, with native host vasculature infiltrating the transplanted human cancer cells, confirming spontaneous hydrogel degradation. Following this, human macrophages were administered via tail vein injection, enhancing the accumulation of mouse immune cells in the humanized tumor twofold and showing murine macrophages adjacent to the vasculature. This study thus provides proof-of-concept for a facile and fully vascularized humanized tumor model in mice for validating immune cell therapies. HIGHLIGHTSO_LIThe oHA was prepared using sodium periodate treatment, which facilitated the formation of in situ CMCTS/oHA hydrogels C_LIO_LICMCTS/oHA hydrogels completely degraded within a short period, allowing for 3D cell condensation C_LIO_LIHigh-density cell-laden CMCTS/oHA hydrogels were injected subcutaneously in mice, resulting in the generation of a vascularized solid tumor C_LIO_LIThe transplanted therapeutic cell was observed to adhere to the tumor tissue through the bloodstream C_LI

bioengineering↗

A novel SARS-CoV-2-derived infectious vector system

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of COVID-19. The development of antiviral drugs for COVID-19 has been hampered by the requirement of a biosafety level 3 (BSL3) laboratory for experiments related to SARS-CoV-2, and by the lack of easy and precise methods for quantification of infection. Here, we developed a SARS-CoV-2 viral vector composed of all four SARS-CoV-2 structural proteins constitutively expressed in lentivirally transduced cells, combined with an RNA replicon deleted for SARS-CoV-2 structural protein genes S, M and E, and expressing a luciferase-GFP fusion protein. We show that, after concentrating viral stocks by ultracentrifugation, the SARS-CoV-2 viral vector is able to infect two human cell lines expressing receptors ACE2 and TMPRSS2. Both luciferase activity and GFP fluorescence were detected, and transduction was remdesivir-sensitive. We also show that this vector is inhibited by three type I interferons (IFN-I) subtypes. Although improvements are needed to increase infectious titers, this vector system may prove useful for antiviral drug screening and SARS-CoV-2-related investigations.

microbiology↗

CBAM-ResNet34-based classification and evaluation method for developmental processes of greenhouse strawberries

Strawberries, known for their economic significance and rich nutritional value, are cultivated extensively worldwide. However, a host of workers need to be employed every year to identify and categorize the developmental stages of the strawberries in the greenhouses, which is not only time-consuming, inefficient, increasing the cultivation cost, but also difficult to guarantee the classification accuracy. Meanwhile, affected by the complicated background, occlusions, and color interference, the features of strawberries are proven challenging to be extracted via the traditional neural networks due to serious gradient disappearance. Therefore, an improved CBAM-ResNet34- based classification evaluation method for developmental processes of greenhouse strawberries is investigated. The procedure of this method is as follows: firstly, the developmental stages of greenhouse strawberries are classified by experts into four stages: Stage I (initial stage), Stage II (green and white fruit stage), Stage III (early ripening stage), and Stage IV (fully ripe stage). The 627, 640, 604, and 340 strawberry images for these four stages are captured. Subsequently, the images are divided into training, validation, as well as testing sets and then undergo image pre- processing, expansion, and augmentation. Whereafter, the 7x7 convolution kernel in the first layer of the network is replaced by three consecutive 3x3 convolution cores to eliminate the redundant weights and unnecessary model parameters, and the BasicBlocks configuration is adjusted. Finally, the CBAM attention mechanism is added to each BasicBlock so as to pinpoint the spatial position of the strawberries and extract their major features such as shape, size, and color. Comparison experiments with the conventional deep neural networks LeNet5, AlexNet, VGG16, ResNet18, ResNet34, and every improved part of CBAM-ResNet34 demonstrated that when the learning rate is 0.001, the Dropout rate is 0.3, and the Adams weight decay parameter is 0.001, the accuracies for validation and testing sets can reach to 92.36% and 87.56% with F1 scores of 0.92, 0.87, 0.85 and 0.88.

plant biology↗

Revolutionizing large-scale DNA synthesis with microchip-based massive in parallel synthesis system

DNA synthesis serves as the fundamental enabling technology of engineering biology, aiming to provide DNA molecules of designed composition, length, and complexity at scale and low cost. Current high-throughput DNA synthesis technologies rely on intricate chip manufacturing and microfluidic systems to provide large-scale synthetic oligonucleotides, at the expense of low concentration and limited compatibility in the processing of longer DNA constructs assembly. Here, we report a microchip-based massive in parallel synthesis (mMPS), pioneering an "identification-sorting-synthesis-recycling" iteration mechanism to microchips for high throughput DNA synthesis. In comparison to microarray-based methods, we demonstrate that our method can increase the DNA product concentration by 4 magnitudes (to picomole-scale per sequence) and greatly simplifies the downstream processes for large-scale gene synthesis construction. By the construction of 1.97 million-diversity variant libraries that cover 1,254 human protein domains, we demonstrated the uniformity of the constructed variant libraries using mMPS-derived oligos is greatly improved, with amino acid distribution highly consistent as designed. In addition, by synthesizing 285 1kb-to-3kb genes with varying degrees of sequence complexity from previously reported strains A501 and 3DAC, potential ancestor of early archaea and bacteria, our result shows that the overall gene assembly success rate using mMPS-derived oligos is increased by 10-fold in comparison to other methods. Our mMPS technology holds the potential to close the gap between the quality and cost of writing DNA in increasing demand across many sectors of research and industrial activities.

synthetic biology↗

Dysregulation of locus-specific repetitive elements in TCGA pan-cancers

Understanding the role of repetitive elements (REs) in cancer development is crucial for identifying novel biomarkers and therapeutic targets. This study investigated the locus-specific dysregulation of REs, including differential expression and methylation of REs, across 12 TCGA cancer types stratified by their genomic context (i.e., genic and intergenic REs). We found uniquely dysregulated genic REs co-regulated with their corresponding transcripts and associated with distinct biological functions in different cancer types. Uniquely dysregulated intergenic REs were identified in each cancer type and used to cluster different sample types. Recurrently dysregulated REs were identified in several cancer types, with genes associated with up-regulated genic REs involved in cell cycle processes and those associated with down-regulated REs involved in the extracellular matrix. Interestingly, 4 out of 5 REs consistently down-regulated in all 12 cancer types were located in the intronic region of the TMEM252, a recently discovered tumor suppressor gene. TMEM252 expression was also down-regulated in 10 of 12 cancer types, suggesting its potential importance across a wide range of cancer types. With the corresponding DNA methylation array data, we found a higher prevalence of hypo-methylated REs in most cancer types (10 out of 12). Despite the slight overlaps between differentially expressed REs and differentially methylated REs, we showed that methylation of locus-specific REs negatively correlates with their expression in some cancer types.

bioinformatics↗

Mechanical control of germ cell specification in Arabidopsis anthers

A central question in developmental biology is how the germline is established. We have studied the specification of the male germ cells (GCs) within the anther1-3. Hereby, we have focused on the potential role of mechanics, an aspect of anther development which has been very poorly characterized2,4. Using a combination of live imaging and mechanical measurements, we provide evidence that GCs originate in a special micro-mechanical niche, where inner tissues exert push on outer cell layers, placing them under compression. Mechanical perturbations significantly disrupted the GC specification and patterning. Moreover, we found that the master genetic regulator SPOROCYTELESS/NOZZLE (SPL/NZZ)5,6 is central in establishing this micro-mechanical environment by softening the cell wall. The mechanical cues, in turn, stabilize the transcription of SPL/NZZ. We propose here an intrinsic growth-derived mechano-chemical feedback loop that drives germ-cell fate acquisition.

developmental biology↗

ATP-gated P2x7 receptor is a major channel type at type II auditory nerves and required for hearing sensitivity efferent controlling and noise protection

Hearing sensitivity and noise protection are mediated and determined by negative feedback of the cochlear efferent system. Type II auditory nerves (ANs) innervate outer hair cells (OHCs) in the cochlea and provide an input to this efferent control. However, little is known about underlying channel information. Here, we report that ATP-gated P2x7 receptor had a predominant expression at type II ANs and the synaptic areas under inner hair cells and OHCs with lateral and medial olivocochlear efferent nerves. Knockout (KO) of P2x7 increased hearing sensitivity with enhanced acoustic startle response (ASR), auditory brainstem response (ABR), and cochlear microphonics (CM) by increasing OHC electromotility, an active cochlear amplifier in mammals. P2x7 KO also increased susceptibility to noise. Middle level noise exposure could impair active cochlear mechanics resulting in permanent hearing loss in P2x7 KO mice. These data demonstrate that P2x7 receptors have a critical role in type II AN function and the cochlear efferent system to control hearing sensitivity; deficiency of P2x7 receptors can impair the cochlear efferent suppression leading to hearing oversensitivity and susceptibility to noise.

neuroscience↗

PSMA-specific CAR-engineered macrophages for therapy of prostate cancer

Chimeric antigen receptor (CAR)-modified macrophages (CAR-Ms) are a promising approach for the treatment of solid tumors due to its high infiltration and immune-regulation activity. Prostate cancer is a typical solid tumor associated with highly immunosuppressive microenvironment. To date, the potential application of CAR-M cell therapy in prostate cancer has been infrequently explored. The prostate-specific membrane antigen (PSMA) functions as a specific biomarker for prostate cancer. In this study, we assessed the antitumor efficacy of PSMA-targeted CAR-Ms in preclinical models. CAR-Ms were engineered to express a PSMA-specific single-chain variable fragment (scFv) and co-stimulatory domains. In vitro data demonstrated specific cytotoxicity of CAR-Ms against PSMA-expressing prostate cancer cells, which was further supported by transcriptome analysis demonstrating the pro-inflammatory phenotypes of CAR-Ms. In vivo studies using xenograft mouse models confirmed significant tumor regression after administration of PSMA-targeted CAR-Ms compared to controls. Histopathological analysis showed infiltration of CAR-Ms into tumor tissues without off-target toxicity. These results highlight the strong antitumor activity and safety of PSMA-targeted CAR-Ms, supporting their potential as a new immunotherapy for prostate cancer.

bioengineering↗

Ultra-low photodamage three-photon microscopy assisted by neural network for monitoring regenerative myogenesis

Three-photon microscopy (3PM) enables high-resolution three-dimensional (3D) imaging in deeply situated and highly scattering biological specimens, facilitating precise characterization of biological morphology and cellular-level physiology in vivo. However, the use of fluorescent probes with relatively low three-photon absorption cross-sections necessitates high-peak-power lasers for excitation, which poses inherent risks of light-induced damage. Additionally, the low repetition frequency of these lasers prolongs scanning time per pixel, hampering imaging speed and exacerbating the potential for photodamage. Such limitations hinder the application of 3PM in studying vulnerable tissues, including muscle regeneration. To address this critical issue, we developed the Multi-Scale Attention Denoising Network (MSAD-Net), a precise and versatile denoising network suitable for diverse structures and varying noise levels. Our network enables the use of lower excitation power (1/4-1/2 of the common power) and shorter scanning time (1/6-1/4 of the common time) in 3PM while preserving image quality and tissue integrity. It achieves an impressive structural similarity index (SSIM) of up to 0.9932 and an incredibly fast inference time of just 80 milliseconds per frame which ensured both high fidelity and practicality for downstream applications. By utilizing MSAD-Net-assisted imaging, we comprehensively characterize the biological morphology and functionality of muscle regeneration processes through deep in vivo five-channel imaging under extremely low excitation power and short scanning time, while maintaining a high signal-to-background ratio (SBR) and excellent axial spatial resolution. Furthermore, we conducted high axial-resolution dynamic imaging of vascular microcirculation, macrophages, and ghost fibers. Our findings provide a deeper understanding of the mechanisms underlying muscle regeneration at the cellular and tissue levels.

developmental biology↗

Genomics-FM: Universal Foundation Model for Versatile andData-Efficient Functional Genomic Analysis

Artificial intelligence (AI) plays a crucial role in functional genomic analysis, offering great potential for comprehending biological phenomena such as heredity, development, diseases, and evolution. However, the development of AI models needs substantial labeled data, and these models are typically task-specific with limited generalizability to various applications. Here, we develop Genomics-FM, a genomic vocabulary driven foundation model that enables versatile and label-efficient functional genomic analysis. Specifically, Genomics-FM is first pretrained with ensemble genomic vocabulary on vast unlabelled data to learn comprehensive and generalizable representations and then finetuned with specific genomic vocabulary on limited labeled data to selectively activate and adapt the pretraining knowledge for specific tasks. We show that Genomics-FM significantly reduces the dependence on labeled data, and demonstrates the capability to outperform existing models across a comprehensive suite of tasks including genome annotation, epigenomic and expression profile prediction, and variant effect assessment. Remarkably, Genomics-FM even shows impressive zero-shot predictive capabilities across diverse species and tissues and exhibits noticeable adaptability to RNA-related tasks. With feasibility in data scarcity and even cross-domain biological scenarios, Genomics-FM will promote the broad application of AI and empower researchers to tackle previously insurmountable challenges, paving the way for groundbreaking research and discoveries.

bioinformatics↗

CircCNNs, a convolutional neural network framework to better understand the biogenesis of exonic circRNAs

Circular RNAs (circRNAs) as biomarkers for cancer detection have been extensively explored, however, the biogenesis mechanism is still elusive. In contrast to linear splicing (LS) involved in linear transcript formation, the so-called back splicing (BS) process has been proposed to explain circRNA formation. To investigate the potential mechanism of BS via the machine learning approach, we curated a high-quality BS and LS exon pairs dataset with evidence-based stringent filtering. Two convolutional neural networks (CNN) base models with different structures for processing splicing junction sequences including motif extraction were created and compared after extensive hyperparameter tuning. In contrast to the previous study, we are able to identify motifs corresponding to well-established BS-associated genes such as MBNL1, QKI, and ESPR2. Importantly, despite prevalent high false positive rates in existing circRNA detection pipelines and databases, our base models demonstrated a notable high specificity (greater than 90%). To further improve the model performance, a novo fast numerical method was proposed and implemented to calculate the reverse complementary matches (RCMs) crossing two flanking regions and within each flanking region of exon pairs. Our CircCNNs framework that incorporated RCM information into the optimal base models further reduced the false positive rates leading to 88% prediction accuracy.

bioinformatics↗