Biology subjects

Chen, S.-H.

Publications and source records attributed to Chen, S.-H..

At least 19 recordsLinked to original sources

bioRxiv2026

Programmable sequence-resolved in situ profiling of glycoRNA-protein interactomes by GlycoRNA-Map

Cell-surface glycoRNAs participate in diverse biological processes, but they were investigated as pooled populations and the protein interactome of individual glycoRNA species remain unresolved. Here we develop GlycoRNA-Map, a programmable photocatalytic proximity-labeling method that maps proteins surrounding sequence-defined endogenous glycoRNAs on living cells. A sialic-acid-binding aptamer and an RNA-hybridization probe jointly recruit a fluorophore-modified oligonucleotide through dual recognition of the glycan and RNA moieties of glycoRNAs. Light-activated biotinylation followed by quantitative mass spectrometry identified 200-418 enriched proteins for each of five glycoRNAs in A549 cells. Comparison of these proteomes revealed limited overlap among different glycoRNA sequences and across cell types, demonstrating that glycoRNA-associated protein environments depend on both RNA identity and cellular context. Transforming growth factor-{beta} receptors 1 and 2 (TGFBR1 and TGFBR2) were identified in the proximal proteomes of multiple glycoRNAs. Removal of cell-surface RNAs enhanced TGF-{beta} receptor signaling and promoted cell migration, demonstrating that glycoRNAs can functionally regulate extracellular signaling by interacting with their protein neighborhoods. GlycoRNA-Map thus provides an accessible strategy for resolving sequence-specific glycoRNA-protein interactome and discovering their roles in membrane signaling.

biochemistry↗

bioRxiv2026

Dynamics of Take-off in Bipedal Animals and Robots

Take-off is a fast and energy-efficient strategy for bipedal animals, such as birds, to achieve rapid movement; however, how muscle physiology scales to govern this universal behavior remains unresolved. Research in other species physiologies is not readily applicable. As a result, important questions, whether theropod dinosaurs such as Tyrannosaurus rex were capable of jumping, remain unanswered. In this article, we coupled Lagrangian dynamics with Hills muscle equations and developed new experimental methods to quantify joint rotational stiffness and damping, thereby enabling a systematic description of lower-limb mechanics. The approach establishes a novel kinetic framework that links muscle contractile properties to lower-limb performance without invoking control optimization. Animal observations and tabletop mechanisms validate the framework. The mechanics model reveals that the take-off time of about 0.1 s across body masses of 0.003 to 90 kg is achievable, as heavier birds generate proportionally higher reaction forces. Additionally, Tyrannosaurus rex should be capable of jumping, based on the available physiology data. Beyond evolutionary insights, our framework provides a new methodology for analyzing the mechanical properties of biological joints and informing the design of scalable bio-inspired robots.

biophysics↗

bioRxiv2026

Molecular Transducers of Physical Activity Consortium (MoTrPAC): Initial Insights into the Dynamic Human Responses to Exercise

The goal of the Molecular Transducers of Physical Activity Consortium (MoTrPAC) is to examine the physiological and molecular basis for health benefits in response to acute and chronic exercise. Prior to COVID-19 suspension, healthy, sedentary participants (N=206, 18-74y) were randomized to endurance exercise (N=80), resistance exercise (N=81), or non-exercise control (N=45) interventions. The prescribed vigorous acute endurance and resistance exercise bouts induced physiological and metabolic perturbations relative to resting homeostasis. The supervised chronic (3d/wk, 12wk) endurance or resistance training programs robustly improved several physiological parameters (i.e., VO2peak, muscular strength). Temporal biospecimen (blood, muscle, and adipose) collections and processing coupled to the acute exercise bouts were highly successful. In most cases, over 90% success was achieved for blood, muscle, and adipose samples. Endurance and resistance exercise induced distinct acute and chronic physiological responses, which provide a framework to interrogate the molecular basis for health adaptations to these two popular exercise modalities. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/705347v1_ufig1.gif" ALT="Figure 1"> View larger version (65K): org.highwire.dtl.DTLVardef@554ee9org.highwire.dtl.DTLVardef@afb28dorg.highwire.dtl.DTLVardef@f381cdorg.highwire.dtl.DTLVardef@cef19c_HPS_FORMAT_FIGEXP M_FIG C_FIG

systems biology↗

bioRxiv2025

Genome assembly of five Tephritid species for the enhancement of the Sterile Insect Technique

Tephritidae insect pests account for extensive crop damage and yield losses globally. Modern, sustainable pest management approaches are species-specific and, therefore, high-quality genome assemblies are required for their application. Here, we present chromosome-level assemblies for five members of the Tephritidae family: Anastrepha fraterculus, Anastrepha ludens, Bactrocera dorsalis, Bactrocera zonata and Zeugodacus cucurbitae. The assemblies used long read sequencing polished with short read sequencing and scaffolded using Hi-C (chromatin conformation capture) sequencing. Prior to scaffolding the assembly deduplication was performed to separate a primary assembly and an alternate assembly, and each was then scaffolded independently. The scaffolded assemblies reached N50 length in the range of 60Mb to 120Mb. The scaffolded assemblies were verified with BUSCO and completeness was in the range 97% to 98.5% and had very low duplicated, fragmented and missing orthologs.

ecology↗

bioRxiv2025

Rictor CRISPR Gene Editing by Lipid Nanoparticle Delivery Stimulates Anti-Tumor Immunity in Breast Cancer Liver Metastasis Model

Triple-negative breast cancer (TNBC) is a highly aggressive subtype, accounting for 10-15% of breast cancer cases in the United States. Liver metastases, common in advanced TNBC, are linked to especially poor outcomes, with a 5-year survival rate of just 11%. Although immune checkpoint inhibitors (ICIs) targeting PD-1 or PD-L1 show promise, durable responses in TNBC remain uncommon. This is largely due to a profoundly immunosuppressive tumor microenvironment (TME), driven by tumor-associated myeloid cells. Tumor-associated macrophages (TAMs) and neutrophils (TANs) polarize into immunosuppressive M2 and N2 phenotypes, respectively, suppressing T cell activity through cytokines, ROS, and checkpoint ligands such as VISTA. Myeloid-derived suppressor cells (MDSCs) further inhibit immunity by depleting nutrients and inducing regulatory T cells. As a result, despite its immunogenic features, TNBC remains resistant to immunotherapy due to persistent myeloid-mediated suppression. Here, we developed ionizable lipid nanoparticles (iLNPs) engineered to deliver the CRISPR-Cas12a ribonuclease complex targeting Rictor, a critical component of mTORC2, for in vivo reprograming of myeloid cells. The intravenous (IV) injection of CRISPR Rictor-targeting iLNP (CR-Ric-LNP) showed efficient uptake by circulating myeloid cells and accumulation into the breast cancer liver metastases. Notably, Rictor gene editing triggered pro-inflammatory activation of myeloid cells in the TME, enhancing antitumor responses. Single-cell RNA sequencing revealed that Rictor silencing treated samples showed induced rapid remodeling of the TME, with a significant reduction in immunosuppressive macrophages within 24 hours of treatment. Concurrently, cytotoxic T-cell populations exhibited increased interferon-gamma (Ifng) production, driving the emergence of specific myeloid clusters that were responsive to Interferon signaling, particularly in macrophages and neutrophils. A shift from an immunosuppressive to an inflammatory TME was further evidenced by an elevated Cxcl10/Spp1 ratio in myeloid cells. CR-Ric-LNP treatment also enhanced T-cell activation, reducing exhausted T cells and regulatory T cells (Tregs) while expanding natural killer (NK) cells, naive CD4+, and CD8+ T cells. These changes correlated with a decreased proportion of tumor cells and proliferating cells, ultimately leading to a significant survival benefit in a 4T1 breast cancer liver metastasis model. Our findings demonstrate that myeloid-targeted Rictor silencing reprograms the TME, promoting antitumor immunity and improving therapeutic outcomes. O_FIG O_LINKSMALLFIG WIDTH=199 HEIGHT=200 SRC="FIGDIR/small/661471v1_ufig1.gif" ALT="Figure 1"> View larger version (109K): org.highwire.dtl.DTLVardef@10a5e7aorg.highwire.dtl.DTLVardef@1c0c005org.highwire.dtl.DTLVardef@17ec6b5org.highwire.dtl.DTLVardef@27c507_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2025

Integrated Spatial Analysis of Ovarian Precancerous Lesions

Studying precancerous lesions is essential for improving early detection and prevention, particularly in aggressive cancers such as ovarian carcinoma. Here, we conducted integrated and spatial analyses of transcriptomes, aneuploidy, and clinic-pathological features in 166 ovarian precancerous lesions. Four pre-cancerous subtypes were identified transcriptomically: proliferative, immunoreactive, dormant, and mixed. These subtypes varied in their frequency of germline-BRCA1/2 mutations, aneuploidy, CCNE1/MYC amplification, proliferative activity, immune-regulatory gene expression, and histological features. Notably, the immunoreactive subtype upregulated immune-regulatory genes, exhibited chronic inflammation, and was enriched in cases with germline-BRCA1/2 mutations, deletions of chromosomes 17 (harboring TP53 and BRCA1) and 13 (harboring BRCA2), leading to a double "two-hit" involving TP53 and BRCA1/2. Tumor invasion was associated with the activation of interferon response pathways, epithelial-mesenchymal transition, and extracellular matrix remodeling. In summary, our results elucidate the earliest molecular landscape of ovarian precancerous lesions, serving as the foundation for future risk stratification to identify aggressive pre-cancerous lesions.

molecular biology↗

bioRxiv2025

Forecast Padding Enhances Accuracy and Robustness of EEG-Phase-Synchronized TMS

Closed-loop neuromodulation is a promising personalized treatment for various neuropsychiatric disor-ders, delivering precise stimuli based on real-time brain signals. However, its clinical potential is currently limited by technical challenges inherent in its real-time nature. This article addresses the primary technical challenges in EEG-Phase-Synchronized Transcranial Magnetic Stimulation (TMS), including poor stimulation accuracy and inefficient biomarker detection (correlated with deadlock). These challenges arise from the vulnerability of existing algorithms to filter edge effects. Inspired by predictive coding theory in neuroscience, we propose a novel signal padding method (forecast padding) to mitigate the filter edge effect. To properly quantify the improvements that forecast padding brings about in real-world systems, we introduce a novel delay-relevant validation framework and demonstrate its reliability using experimental data from a real system. Through this framework, we demonstrate that forecast padding significantly improves both stimulation accuracy and deadlock rate. Given the pervasive impact of filter edge effects in closed-loop neuromodulation and other signal processing domains, forecast padding shows broad application potential across various fields.

bioengineering↗

bioRxiv2025

Proteomic Analysis of Endemic Viral Infections in Neuronsoffers Insights into Neurodegenerative Diseases

Endemic viral infections with low pathogenicity are often overlooked due to their mild symptoms, yet they can exert long-term effects on cellular function and contribute to disease pathogenesis. While viral infections have been implicated in neurodegenerative disorders, their impact on the neuronal proteome remains poorly understood. Here, we differentiated human induced pluripotent stem cells (KOLF2.1J) into mature neurons to investigate virus-induced proteomic changes following infection with five neurotropic endemic human viruses: Herpes simplex virus 1 (HSV-1), Human coronavirus 229E (HCoV-229E), Epstein-Barr virus (EBV), Varicella-Zoster virus (VZV), and Influenza A virus (H1N1). Given that these viruses can infect adults and have the potential to cross the placental barrier, their molecular impact on neurons may be relevant across the lifespan. Using mass spectrometry-based proteomics with a customized library for simultaneous detection of human and viral proteins, we confirmed successful infections and identified virus-specific proteomic signatures. Notably, virus-induced protein expression changes converged on key neuronal pathways, including those associated with neurodegeneration. Gene co-expression network analysis identified protein modules correlated with viral proteins. Pathway enrichment analysis of these modules revealed associations with the nervous system, including pathways linked to Alzheimers and Parkinsons disease. Remarkably, several viral-induced proteomic alterations overlapped with changes observed in postmortem Alzheimers patient brains, suggesting a mechanistic connection between viral exposure and neurodegenerative disease progression. These findings provide molecular insights into how common viral infections perturb neuronal homeostasis and may contribute to neurodegenerative pathology, highlighting the need to consider endemic viruses as potential environmental risk factors in neurological disorders.

neuroscience↗

bioRxiv2023

A Novel Genome Optimization Tool for Chromosome-Level Assembly across Diverse Sequencing Techniques

This paper introduces a novel genome assembly optimization tool named LOCLA, which stands for "Local Optimization for Chromosome-Level Assembly". It identifies reads and contigs aligned locally with high quality on gap flanks or scaffold boundaries of draft assemblies for gap filling and scaffold connection. LOCLA applies to both de novo and reference-based assemblies. It can also utilize reads produced by diverse sequencing techniques, e.g., 10x Genomics (10xG) Linked-Reads, and PacBio HiFi reads. We validated LOCLA on three human samples and one non-model organism. For the first two human samples, LLD0021C and CHM13, we generated de novo draft assemblies from 10xG Linked-Reads. On LLD0021C, LOCLA improves the draft assembly by adding 23.3 million bases using only 10xG Linked-Reads. These additional bases cover 28,746 protein-coding regions, particularly in pericentromeric and telomeric regions. On the CHM13 sample, we took 10xG Linked-Reads and PacBio HiFi reads as input. As a result, LOCLA added 46.2 million bases to the draft assembly. The increased content enables us to identify genes linked to complex diseases (e.g., ARHGAP11A) and critical biological pathways. We created two reference-guided draft assemblies on the third human sample, HG002, using contigs assembled from PacBio HiFi reads. LOCLA enhances the two draft assemblies by recovering 27.9 million bases (22.26%) and 35.7 million bases (30.93%) of the sequences discarded by the reference-guided assembly tool. The results indicate the robustness of LOCLAs contig detection algorithm on gap flanks. Furthermore, we show that 95% of the sequences filled in by LOCLA have over 80% accuracy compared with the HG002 reference genome published by the Human Pan-genome Reference Consortium. On the non-model organism, LOCLA enhanced the genome assembly of Bruguiera sexangula (JAHLGP000000000) by decreasing 41.4% of its gaps and raising the Benchmarking Universal Single-Copy Orthologs (BUSCO) analysis score to 98.10%. LOCLA can optimize de novo and reference-guided assemblies using varied sequencing reads. The final assemblies produced by LOCLA have improved in both quantity and quality. The increased gene content may provide a valuable resource in advancing personalized medicine.

genomics↗

bioRxiv2023

Inhibition mechanism and antiviral activity of an α-ketoamide based SARS-CoV-2 main protease inhibitor

SARS-CoV-2 has demonstrated extraordinary ability to evade antibody immunity by antigenic drift. Small molecule drugs may provide effective therapy while being part of a solution to circumvent SARS-CoV-2 immune escape. In this study we report an -ketoamide based peptidomimetic inhibitor of SARS-CoV-2 main protease (Mpro), RAY1216. Enzyme inhibition kinetic analysis established that RAY1216 is a slow-tight inhibitor with a Ki of 8.6 nM; RAY1216 has a drug-target residence time of 104 min compared to 9 min of PF-07321332 (nirmatrelvir), the antiviral component in Paxlovid, suggesting that RAY1216 is approximately 12 times slower to dissociate from the protease-inhibitor complex compared to PF-07321332. Crystal structure of SARS-CoV-2 Mpro:RAY1216 complex demonstrates that RAY1216 is covalently attached to the catalytic Cys145 through the -ketoamide warhead; more extensive interactions are identified between bound RAY1216 and Mpro active site compared to PF-07321332, consistent with a more stable acyl-enzyme inhibition complex for RAY1216. In cell culture and human ACE2 transgenic mouse models, RAY1216 demonstrates comparable antiviral activities towards different SARS-CoV-2 virus variants compared to PF-07321332. Improvement in pharmacokinetics has been observed for RAY1216 over PF-07321332 in various animal models, which may allow RAY1216 to be used without ritonavir. RAY1216 is currently undergoing phase III clinical trials (https://clinicaltrials.gov/ct2/show/NCT05620160) to test real-world therapeutic efficacy against COVID-19.

biochemistry↗

bioRxiv2023

Constitutive protein degradation induces acute cell death via proteolysis products

Modulation of proteolysis is an emerging therapeutic mainstay. The clinical success of thalidomide and analogs has inspired development of rationally-designed therapeutics that repurpose endogenous degradation machinery to target pathogenic proteins. However, it is unknown whether target removal is the critical effect that drives degrader-induced efficacy. Here we report that proteasome-generated peptides actively initiate degrader-induced cell death. Utilizing BET family degraders as exemplars, we find that induced proteasomal degradation of the BRD4-long isoform (BRD4-L) generates neo-amino-terminal peptides that neutralize Inhibitor of Apoptosis (IAP) proteins to precipitate cell death. Depletion of BRD4-L paradoxically suppresses caspase activation induced by numerous BET degraders. An unbiased screen revealed that other degrader compounds, including clinical CELMoDs, rely on the same mechanism to potentiate caspase activation and apoptosis. Finally, in the context of constitutive immunoglobulin proteostasis within multiple myeloma cells, we report that therapeutic proteasomal protease inhibition alters the peptide repertoire to neutralize IAPs, thus contributing to the clinical efficacy of bortezomib. Together, these findings clarify the counterintuitive clinical benefit achieved by combining thalidomide analogs with proteasome inhibitors. Our study reveals a previously unrealized pro-apoptotic function of the peptides generated by a variety of proteolysis-modulating compounds, that provide design considerations to maximize therapeutic benefit.

cell biology↗

bioRxiv2023

Natural evolution of SARS-CoV-2 variants in K18-ACE2 mice gives rise to more virulent virus and variant alleles associated with treatment resistance.

The persistence of COVID-19 is partly due to viral evolution reducing vaccine and treatment efficacy. Serial infections of Wuhan-like SARS-CoV-2 in Balb/c mice yielded mouse-adapted strains with greater infectivity and mortality. We investigated if passaging unmodified B.1.351 (Beta) and B.1.617.2 (Delta) 20 times in K18-ACE2 mice, expressing human ACE2 receptor, in a BSL-3 laboratory without selective pressures, would drive human health-relevant evolution and if evolution was lineage-dependent. Late-passage virus caused more severe disease, at organism and lung tissue scales, with late-passage Delta demonstrating antibody resistance and interferon suppression. This resistance co-occurred with a de novo spike S371F mutation, linked with both traits. S371F, an Omicron-characteristic mutation, was co-inherited at times with spike E1182G per Nanopore sequencing, existing in different quasi-species at others. Both are linked to mammalian GOLGA7 and ZDHHC5 interactions, which mediate viral-cell entry and antiviral response. This study demonstrates SARS-CoV-2s tendency to evolve with phenotypic consequences, its evolution varying by lineage, and suggests non-dominant quasi-species contribute.

genetics↗

bioRxiv2022

Evaluation of endogenous and therapeutic 25-hydroxycholesterols in murine models of pulmonary SARS-CoV-2 infection

Oxysterols (i.e., oxidized cholesterol species) have complex roles in biology. 25-hydroxycholesterol (25HC), a product of activity of cholesterol-25-hydroxylase (CH25H) upon cholesterol, has recently been shown to be broadly antiviral, suggesting therapeutic potential against SARS-CoV-2. However, 25HC can also amplify inflammation and tissue injury and be converted by CYP7B1 to 7,25HC, a lipid with chemoattractant activity via the G protein-coupled receptor, EBI2/GPR183. Here, using in vitro studies and two different murine models of SARS-CoV-2 infection, we investigate the effects of these two oxysterols on SARS-CoV-2 pneumonia. We show that while 25HC and enantiomeric-25HC are antiviral in vitro against human endemic coronavirus-229E, they did not inhibit SARS-CoV-2; nor did supplemental 25HC reduce pulmonary SARS-CoV-2 titers in the K18-human ACE2 mouse model in vivo. 25HC treatment also did not alter immune cell influx into the airway, airspace cytokines, lung pathology, weight loss, symptoms, or survival but was associated with increased airspace albumin, an indicator of microvascular injury, and increased plasma pro-inflammatory cytokines. Conversely, mice treated with the EBI2/GPR183 inhibitor NIBR189 displayed a modest increase in lung viral load only at late time points, but no change in weight loss. Consistent with these findings, although Ch25h was upregulated in the lungs of SARS-CoV-2-infected WT mice, lung viral titers and weight loss in Ch25h-/- and Gpr183-/- mice infected with the beta variant were similar to control animals. Taken together, endogenous 25-hydroxycholesterols do not significantly regulate early SARS-CoV-2 replication or pathogenesis and supplemental 25HC may have pro-injury rather than therapeutic effects in SARS-CoV-2 pneumonia.

immunology↗

bioRxiv2022

Peptide-based drug predictions for cancer therapy using deep learning

BackgroundTherapeutic drugs used in cancer treatment have ineffectiveness and resistance to drug action problems. Anticancer peptides (ACPs) are selective and toxic to cancer cells and quickly produced. Thus, ACPs can be a satisfactory substitute for therapeutic drugs. We developed AI4ACP, a user-friendly web-server ACP predictor that can predict the anticancer property of query peptides, thus promoting the discovery of peptides with anticancer activity. ResultOur results revealed that the performance of our ACP predictor trained using the new ACP collection was superior to that of the available high-performance ACP predictors. ConclusionsAI4ACP is a user-friendly web-server ACP predictor that can be used to determine whether a query sequence is an ACP. This tool can be beneficial for drug development for cancer treatment. AI4ACP is freely accessible at https://axp.iis.sinica.edu.tw/AI4ACP/

cancer biology↗

bioRxiv2022

A Saturated Map of Common Genetic Variants Associated with Human Height from 5.4 Million Individuals of Diverse Ancestries

Common SNPs are predicted to collectively explain 40-50% of phenotypic variation in human height, but identifying the specific variants and associated regions requires huge sample sizes. Here we show, using GWAS data from 5.4 million individuals of diverse ancestries, that 12,111 independent SNPs that are significantly associated with height account for nearly all of the common SNP-based heritability. These SNPs are clustered within 7,209 non-overlapping genomic segments with a median size of ~90 kb, covering ~21% of the genome. The density of independent associations varies across the genome and the regions of elevated density are enriched for biologically relevant genes. In out-of-sample estimation and prediction, the 12,111 SNPs account for 40% of phenotypic variance in European ancestry populations but only ~10%-20% in other ancestries. Effect sizes, associated regions, and gene prioritization are similar across ancestries, indicating that reduced prediction accuracy is likely explained by linkage disequilibrium and allele frequency differences within associated regions. Finally, we show that the relevant biological pathways are detectable with smaller sample sizes than needed to implicate causal genes and variants. Overall, this study, the largest GWAS to date, provides an unprecedented saturated map of specific genomic regions containing the vast majority of common height-associated variants.

genetics↗

bioRxiv2021

Developing an Antiviral Peptides Predictor with Generative Adversarial Network Data Augmentation

MotivationNew antiviral drugs are urgently needed because of emerging viral pathogens increasing severity and drug resistance. Antiviral peptides (AVPs) have multiple antiviral properties and are appealing candidates for antiviral drug development. We developed a sequence-based binary classifier to identify whether an unknown short peptide has AVP activity. We collected AVP sequence data from six existing databases. We used a generative adversarial network to augment the number of AVPs in the positive training dataset and allow our deep convolutional neural network model to train on more data. ResultsOur classifier achieved outstanding performance on the testing dataset compared with other state-of-the-art classifiers. We deployed our trained classifier on a user-friendly web server. Availability and implementationAI4AVP is freely accessible at http://axp.iis.sinica.edu.tw/AI4AVP/ Contactcylin@iis.sinica.edu.tw Supplementary informationSupplementary data is also available.

microbiology↗

bioRxiv2021

Discovering Novel Antimicrobial Peptides in Generative Adversarial Network

Due to the growing number of clinical antibiotic resistance cases in recent years, novel antimicrobial peptides (AMPs) can become ideal for next-generation antibiotics. This study trained a deep convolutional generative adversarial network (GAN) with known AMPs to generate novel AMP candidates. The quality of the GAN-designed peptides was evaluated in silico, and eight of them named GAN-pep 1[~]8 were chosen to be synthesized for further experiments. Disk diffusion testing and minimum inhibitory concentration (MIC) determination were used to determine the antibacterial effects of the synthesized GAN-designed peptides. Seven out of the eight synthesized GAN-designed peptides showed antibacterial activities. Additionally, GAN-pep 3 and GAN-pep 8 had a broad spectrum of antibacterial effects. Both of them were also effective against antibiotic-resistant bacteria strains such as methicillin-resistant Staphylococcus aureus (S. aureus) and carbapenem-resistant Pseudomonas aeruginosa (P. aeruginosa). GAN-pep 3, the most promising GAN-designed peptide candidate, had low MICs against all the tested bacteria.

microbiology↗

bioRxiv2021

GABOLA: A Reliable Gap-Filling Strategy for de novo Chromosome-Level Assembly

We propose a novel method, GABOLA, which utilizes long-range genomic information provided by accurate linked short reads jointly with long reads to improve the integrity and resolution of whole genome assemblies especially in complex genetic regions. We validated GABOLA on human and Japanese eel genomes. On the two human samples, we filled in more bases spanning 23.3Mbp and 46.2Mbp than Supernova assembler, covering over 3,200 functional genes which includes 8,500 exons and 15,000 transcripts. Among them, multiple genes related to various types of cancer were identified. Moreover, we discovered additional 11,031,487 base pairs of repeat sequences and 218 exclusive repeat patterns, some of which are known to be linked to several disorders such as neuron degenerative diseases. As for the eel genome, we successfully raised the genetic benchmarking score to 94.6% while adding 24.7 million base pairs. These results manifest the capability of GABOLA in the optimization of whole genome assembly and the potential in precise disease diagnosis and high-quality non-model organism breeding. Availability: The docker image and source code of GABOLA assembler are available at https://hub.docker.com/r/lsbnb/gabola and https://github.com/lsbnb/gabola respectively.

genomics↗