Biology subjects

Liu, Y.

Publications and source records attributed to Liu, Y..

At least 1,171 records · Page 65Linked to original sources

bioRxiv2024

The Hippo/YAP Pathway Mediates the De-differentiation of Corneal Epithelial Cells into Functional Limbal Epithelial Stem Cells In Vivo

Regeneration after tissues injury is often associated with cell fate plasticity, which restores damaged or lost cells. The de-differentiation of corneal epithelial cells (CECs) into functional stem cells after the ablation of innate stem cells, known as limbal epithelial stem cells (LESCs), remains controversial. In this study, we showed the functional maintenance of corneal epithelium after the ablation of innate stem cells, and the regeneration of functional LESCs, which maintained corneal transparency, prevented corneal conjunctivalization and participated in the wound healing. Subsequent intravital lineage tracing revealed that CECs could de-differentiate into active or quiescent LESCs, which functioned as well as their innate counterparts. Furthermore, the de-differentiation of CECs required an intact limbal niche, and the outcome of the competition between conjunctival and corneal epithelium for the limbal niche determined whether the de-differentiation would occur or not. Mechanically, the suppression of YAP signal promoted the de-differentiation of CECs after the ablation of innate stem cells, while the persistent activation of YAP prevented the de-differentiation of CECs after an additional alkali burn to the limbal stroma. These results will pave the way for an alternative approach to treat limbal stem cell deficiency (LSCD) by modulating the de-differentiation of CECs in vivo.

cell biology↗

bioRxiv2024

Brain-derived exosomal hemoglobin transfer contributes to neuronal mitochondrial homeostasis under hypoxia

Hypoxia is an important physiological stress causing nerve injuries and several brain diseases. However, the mechanism of brain response to hypoxia remains unclear, thus limiting the development of interventional strategies. This study conducted combined analyses of single-nucleus transcriptome sequencing and extracellular vesicle transcriptome sequencing on hypoxic mouse brains, described cell-cell communication in the brain under hypoxia from intercellular and extracellular dimensions, confirmed that hemoglobin mRNA was transferred from non-neuronal cells to neurons, and eventually expressed. Then we further explored the role of exosomal hemoglobin transfer in vitro, clarified that hypoxia promoted the transfer and expression of exosomal hemoglobin between endothelial cells and neurons. And we found the vital function of exosomal hemoglobin to protect against neurological injury by maintaining mitochondrial homeostasis in neurons. In conclusion, this study identified a novel mechanism of mutual aid in hypoxia responses in the brain, involving exosomal hemoglobin transfer, clarified the important role of exosomal communication in the process of brain stress response, and provided a novel interventional perspective for hypoxia-related brain diseases.

cell biology↗

bioRxiv2024

Transcriptional reprogramming deploys a compartmentalized "timebomb" in Catharanthus roseus to fend off chewing herbivores

The evolutionary arms-race between plants and insects has led to key adaptive innovations that drive diversification. Alkaloids are well-documented anti-herbivory compounds in plant chemical defenses, but how these specialized metabolites are allocated to cope with both biotic and abiotic stresses concomitantly is largely unknown. To examine how plants prioritize their metabolic resources responding to herbivory and cold, we integrated dietary toxicity bioassay in insects with co-expression analysis, hierarchical clustering, promoter assay, and protein-protein interaction in plants. Catharanthus roseus, a medicinal plant known for its insecticidal property against chewing herbivores, produces two terpenoid indole alkaloid monomers, vindoline and catharanthine. Individually, they exhibited negligible toxicity against Manduca sexta, a chewing herbivore; their condensed product, anhydrovinblastine, however, was highly toxic. Such unique insecticidal mode of action demonstrates that terpenoid indole alkaloid "timebomb" can only be activated when the two spatially isolated monomeric precursors are dimerized by herbivory. Without initial selection pressure and apparent fitness costs, this adaptive chemical defense against herbivory is innovative and sustainable. The biosynthesis of insecticidal terpenoid indole alkaloids is induced by herbivory but suppressed by cold. Here, we identified a transcription factor, Herbivore Induced Vindoline-gene Expression (HIVE), that coordinates the production of terpenoid indole alkaloids in response to herbivory and cold stress. The HIVE-mediated transcriptional reprogramming allows this herbaceous perennial to allocate their metabolic resources for chemical defense at a normal temperature, when herbivory pressure is high, but switches to cold tolerance under a cooler temperature, when insect infestation is secondary.

plant biology↗

bioRxiv2024

Age-Associated Genetic and Environmental Contributions to Epigenetic Aging Across Adolescence and Emerging Adulthood

BackgroundEpigenetic aging estimators commonly track chronological and biological aging, quantifying its accumulation (i.e., epigenetic age acceleration) or speed (i.e., epigenetic aging pace). Their scores reflect a combination of inherent biological programming and the impact of environmental factors, which are suggested to vary at different life stages. The transition from adolescence to adulthood is an important period in this regard, marked by an increasing and, then, stabilizing epigenetic aging variance. Whether this pattern arises from environmental influences or genetic factors is still uncertain. This study delves into understanding the genetic and environmental contributions to variance in epigenetic aging across these developmental stages. Using twin modeling, we analyzed four estimators of epigenetic aging, namely Horvath Acceleration, PedBE Acceleration, GrimAge Acceleration, and DunedinPACE, based on saliva samples collected at two timepoints approximately 2.5 years apart from 976 twins of four birth cohorts (aged about 9.5, 15.5, 21.5, and 27.5 years at first and 12, 18, 24, and 30 years at second measurement occasion). ResultsHalf to two-thirds (50-68%) of the differences in epigenetic aging were due to unique environmental factors, indicating the role of life experiences and epigenetic drift, besides measurement error. The remaining variance was explained by genetic (Horvath Acceleration: 24%; GrimAge Acceleration: 32%; DunedinPACE: 47%) and shared environmental factors (Horvath Acceleration: 26%; PedBE Acceleration: 47%). The genetic and shared environmental factors represented the primary sources of stable differences in corresponding epigenetic aging estimators over 2.5 years. Age moderation analyses revealed that the variance due to individually-unique environmental sources was smaller in younger than in older cohorts in epigenetic aging estimators trained on chronological age (Horvath Acceleration: 47% to 49%; PedBE Acceleration: 33% to 68%). The variance due to genetic contributions, in turn, potentially increased across age groups for epigenetic aging estimators trained in adult samples (Horvath Acceleration: 18% to 39%; GrimAge Acceleration: 24% to 43%; DunedinPACE: 42% to 57%). ConclusionsTransition to adulthood is a period of the increasing variance in epigenetic aging. Both environmental and genetic factors contribute to this trend. The degree of environmental and genetic contributions can be partially explained by the design of epigenetic aging estimators.

genomics↗

bioRxiv2024

Cross-modality representation and multi-sample integration of spatially resolved omics data

Spatially resolved sequencing technologies have revolutionized our understanding of biological regulatory processes within the microenvironment by accessing the states of genomic regions, genes and proteins as well as spatial coordinates of cells. However, discrepancies between different modalities and samples hinder the analysis of spatial omics data, necessitating the development of advanced computational methods. In this article, we propose PRESENT, an effective and scalable contrastive learning framework, for the cross-modality representation and multi-sample integration of spatial multi-omics, epigenomics and transcriptomics data. Through comprehensive experiments on spatial datasets, PRESENT demonstrates superior performance across various species, tissues, and technologies. Specifically, PRESENT effectively integrates spatial dependency and omics information simultaneously, facilitating the detection of spatially functional domains and the exploration of biological regulatory mechanisms. Furthermore, PRESENT can be extended for the integrative analysis of tissue samples across different dissected regions or developmental stages, promoting the identification of hierarchical structures from systematic and spatiotemporal perspectives.

bioinformatics↗

bioRxiv2024

Monocytes Mobilized by Gut Neurons Remodel the Enteric Nervous System

The proper organization of the enteric nervous system (ENS) is critical for normal gastrointestinal (GI) physiology. Inflammatory bowel disease (IBD) dysregulates GI physiology, including bowel movements (motility), but in many IBD patients, GI motility disorders persist in remission through a poorly understood pathological process. Here we uncover that post-inflammatory GI dysmotility (PI-GID) stems from structural ENS remodeling driven by a combination of neuronal loss and neurogenesis. Enteric neurons respond to mucosal inflammation by upregulating CCL2 expression and facilitating the recruitment of CCR2+ monocytes into the neural myenteric plexus within the intestinal muscle. This is followed by the expansion of monocyte-derived macrophages and their migration into the myenteric ganglia and phagocytosis of neurons. However, excessive recruitment of monocytes results in disproportionate ENS remodeling and PI-GID. The expansion of inflammatory cells is known to promote tissue hypoxia. We find that enteric neurons become hypoxic upon colitis, but hypoxia-induced signaling via HIF1 initiates an adaptation program in enteric neurons to attenuate CCL2 expression and limit monocyte recruitment. We demonstrate that reinforcing HIF1 signaling in enteric neurons prevents PI-GID by reducing colitis-associated monocyte recruitment in the myenteric plexus and protecting against ENS remodeling. In summary, our findings unveil PI-GID pathogenesis and identify a regulatory axis for its prevention. One Sentence SummaryIntestinal mucosal inflammation engages enteric neurons in the inflammatory response leading to neurogenic recruitment of monocytes into the extra-mucosal myenteric plexus followed by pathological structural remodeling of the enteric nervous system by monocyte-derived macrophages.

immunology↗

bioRxiv2024

The RAE1-STOP1 Module Reduces Sensitivity to Exogenous ABA Treatment by Regulating ABI5 in Arabidopsis

The SENSITIVE TO PROTON RHIZOTOXICITY 1 (STOP1) transcription factor plays a pivotal role in maintaining cellular ion balance and governing aluminum tolerance in plants. Abscisic acid (ABA) participates in aluminum tolerance by inducing the expression of several genes that are STOP1 targets. However, the mechanisms underlying ABA signaling and STOP1-mediated gene expression remain poorly understood. The F-box protein RAE1, an SCF-type E3 ligase component, recognizes STOP1 and controls its ubiquitination and degradation. This study revealed that exogenous ABA supplementation reduced STOP1 levels by promoting the expression of RAE1. Notably, both RAE1 loss-of-function mutants and STOP1 overexpressing lines showed enhanced sensitivity to exogenous ABA treatment, which correlated with early stage post-transcriptional upregulation of ABSCISIC ACID INSENSITIVE5 (ABI5). Our observations strongly suggest that RAE1 operates as an ABA-responsive factor, exerting control over STOP1 homeostasis, and thus establishing a negative feedback loop that controls ABA responses in Arabidopsis. Thus, our study revealed a novel function of the RAE1-STOP1 module in ABA signaling, highlighting its role in reducing ABA sensitivity by preventing ABI5 increase. Single Sentence SummaryF-box protein RAE1 functions as an exogenous ABA responsive mediator to reduce STOP1-mediated ABA sensitivity.

plant biology↗

bioRxiv2024

Potent and broadly neutralizing antibodies against sarbecoviruses elicited by single ancestral SARS-CoV-2 infection

Monoclonal antibody (mAb) therapeutics hold promise for both preventing and treating infectious diseases, especially among vulnerable populations. However, the emergence of various variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents challenges for current mAb treatments, emphasizing the need for more potent and broadly neutralizing antibodies. In this study, we employed an unbiased screening approach to discover broadly neutralizing antibodies and successfully isolated two mAbs from individuals with only exposure to ancestral SARS-CoV-2. One of these antibodies, CYFN1006-1, exhibited robust cross-neutralization against a spectrum of SARS-CoV-2 variants, including the latest JN.1 and KP.2 variants, with consistent IC50 values ranging from [~]1 to 5 ng/mL. Notably, it also displayed broad neutralization activity against SARS-CoV and related sarbecoviruses, such as WIV1, SHC014, RaTG13, and GD-Pangolin. Structural analysis revealed that these mAbs target shared hotspot but mutation-resistant epitopes, with their Fabs locking the RBD in the "down" conformation through interactions with adjacent Fabs and RBDs, and cross-linking Spike trimers into di-trimers to block viral infection. In vivo studies conducted in a JN.1-infected hamster model validated the protective efficacy of CYFN1006-1, emphasizing its therapeutic potential. These findings suggest that, through meticulous approaches, rare antibodies with cross-neutralization activities against SARS-CoV-2 and related sarbecoviruses can be identified from individuals with exclusively ancestral virus exposure.

microbiology↗

bioRxiv2024

An organoid co-culture model for probing systemic anti-tumor immunity in lung cancer

Deciphering the interactions between tumor micro- and systemic immune macro-environment is essential for developing more effective cancer diagnosis and treatment strategies. Here, we established a gel-liquid interface (GLI) co-culture of lung cancer organoids (LCOs) and paired peripheral blood mononuclear cells (PBMCs), featuring with enhanced interactions of immune cells and tumor organoids, to mimic the in vivo systemic anti-tumor immunity induced by immune checkpoint inhibitors (ICI). The co-culture model recapitulates the in vivo ICI-induced T cell recruitment and subsequent tumor regression, predicting the clinical results precisely. We demonstrated that circulating tumor-reactive T cells, which are effector memory-like with high expression levels of GNLY, CD44 and CD9, can serve as an indicator of the immunotherapy efficacy. Interestingly, enhanced inflammatory signaling in blood T cells is accompanied with prompted exhaustion and compromised anti-tumor function, when encountering with organoids. Our findings suggest that the GLI co-culture can be used for developing diagnostic strategies for precision immunotherapies as well as understanding the underlying mechanisms. Summary figure O_FIG O_LINKSMALLFIG WIDTH=178 HEIGHT=200 SRC="FIGDIR/small/597327v1_ufig1.gif" ALT="Figure 1"> View larger version (48K): org.highwire.dtl.DTLVardef@a0829dorg.highwire.dtl.DTLVardef@1df3083org.highwire.dtl.DTLVardef@1ea1065org.highwire.dtl.DTLVardef@1da9464_HPS_FORMAT_FIGEXP M_FIG C_FIG

cancer biology↗

bioRxiv2024

Cell-Graph Compass: Modeling Single Cells with Graph Structure Foundation Model

Inspired by the advancements in pre-trained Large Language Models, there has been a surge of studies in the Life Sciences focusing on constructing foundation models with large scale single-cell RNA-seq data. These studies typically involve pre-training a transformer model on large-scale single-cell sequencing data, followed by fine-tuning for a variety of downstream tasks, achieving notable performance. However, these models all share a common short-coming: to utilize the transformer architecture, originally designed for textual data, they artificially impose a sequential structure on genes within cells, simplifying the complex interactions between genes. Furthermore, they focus solely on transcriptomic data, neglecting other relevant biological information. To address these issues, here we introduce Cell-Graph Compass (CGC), the first foundational model that leverages graph structures to model single cells and describes cells from multiple perspectives, including transcriptional profiles, gene text summaries, transcription factor regulatory networks, gene co-expression patterns, and gene positional relationships. By incorporating self-attention mechanisms, we pretrained the model on 50 million human single-cell sequencing data, resulting in a robust digital representation of cells. Extensive downstream experiments demonstrate that our approach can capture meaningful biological knowledge and achieve superior results in various problem scenarios, achieving the state-of-the-art (SOTA).

bioinformatics↗

bioRxiv2024

A mouse model of TB-associated lung fibrosis reveals persistent inflammatory macrophage populations during treatment

Post-TB lung disease (PTLD) causes a significant burden of global disease. Fibrosis is a central component of many clinical features of PTLD. To date, we have a limited understanding of the mechanisms of TB-associated fibrosis and how these mechanisms are similar to or dissimilar from other fibrotic lung pathologies. We have adapted a mouse model of TB infection to facilitate the mechanistic study of TB-associated lung fibrosis. We find that the morphologies of fibrosis that develop in the mouse model are similar to the morphologies of fibrosis observed in human tissue samples. Using Second Harmonic Generation (SHG) microscopy, we are able to quantify a major component of fibrosis, fibrillar collagen, over time and with treatment. Inflammatory macrophage subpopulations persist during treatment; matrix remodeling enzymes and inflammatory gene signatures remain elevated. Our mouse model suggests that there is a therapeutic window during which adjunctive therapies could change matrix remodeling or inflammatory drivers of tissue pathology to improve functional outcomes after treatment for TB infection.

microbiology↗

bioRxiv2024

Genome-wide mapping of native co-localized G4s and R-loops in living cells

The non-B DNA structures can act as dynamic functional genomic elements regulating gene expression. Among them, G4s and R-loops are two of the best studied. The interplay between R-loops and G4s are emerging in regulating DNA repair, replication and transcription. A comprehensive picture of native co-localized G4s and R-loops in living cells is currently lacking. Here, we describe the development of HepG4-seq and an optimized HBD-seq methods, which robustly capture native G4s and R-loops, respectively, in living cells. We successfully employed these methods to establish comprehensive maps of native co-localized G4s and R-loops in human HEK293 cells and mouse embryonic stem cells (mESCs). We discovered that co-localized G4s and R-loops are dynamically altered in a cell type-dependent manner and are largely localized at active promoters and enhancers of transcriptional active genes. We further demonstrated the helicase Dhx9 as a direct and major regulator that modulates the formation and resolution of co-localized G4s and R-loops. Depletion of Dhx9 impaired the self-renewal and differentiation capacities of mESCs by altering the transcription of co-localized G4s and R-loops - associated genes. Taken together, our work established that the endogenous co-localized G4s and R-loops are prevalently persisted in the regulatory regions of active genes and are involved in the transcriptional regulation of their linked genes, opening the door for exploring broader roles of co-localized G4s and R-loops in development and disease.

genomics↗

bioRxiv2024

Parallel Analyses by Mass Spectrometry (MS) and Reverse Phase Protein Array (RPPA) Reveal Complementary Proteomic Profiles in Triple-Negative Breast Cancer (TNBC) Patient Tissues and Cell Cultures

High-plex proteomic technologies have made substantial contributions to mechanism studies and biomarker discovery in complex diseases, particularly cancer. Despite technological advancements, inherent limitations in individual proteomic approaches persist, impeding the achievement of comprehensive quantitative insights into the proteome. In this study, we employed two widely used proteomic technologies, Mass Spectrometry (MS) and Reverse Phase Protein Array (RPPA) to analyze identical samples, aiming to systematically assess the outcomes and performance of the different technologies. Additionally, we sought to establish an integrated workflow by combining these two proteomic approaches to augment the coverage of protein targets for discovery purposes. We used fresh frozen tissue samples from triple-negative breast cancer (TNBC) and cell line samples to evaluate both technologies and implement this dual-proteomic strategy. Using a single-step protein denaturation and extraction protocol, protein samples were subjected to reverse phase chromatography (LC) followed by electrospray ionization (ESI)-mediated MS/MS for proteomic profiling. Concurrently, identical sample aliquots were analyzed by RPPA for profiling of over 300 proteins and phosphoproteins that are in key signaling pathways or druggable targets in cancer. Both proteomic methods demonstrated the expected ability to differentiate samples by groups, revealing distinct proteomic patterns under various experimental conditions, albeit with minimal overlap in identified targets. Mechanism-based analysis uncovered divergent biological processes identified with the two proteomic technologies, capitalizing on their complementary exploratory potential.

cancer biology↗

bioRxiv2024

Coral hosts actively accumulate inorganic carbon for zooxanthellae to maintain symbiotic relationships

High primary productivity of coral reefs is widely attributed to the mutualistic symbiosis between coral hosts and their microalgal partners (Symbiodiniaceae). Although the mechanisms maintaining this symbiosis have been considerable investigated, how the symbiont microalgae within coral get sufficient CO2 for photosynthesis still remains inadquately explored. Here, we hypothesized that corals may actively accumulate dissolved inorganic carbon (DIC) for microalgae to maintain the symbiosis. Carbon (HCO3- and glucose) supply and consumption were evaluated in the scleractinian coral (Goniopora lobata) and its symbiont under light and dark conditions. Results suggest that Symbiodiniaceae were high DIC consumers, requiring about 2-3 fold more DIC than free-living species. The corals were high DIC producers, with internal concentrations up to 4.2 fold higher than in the surrounding seawater. In the absence of microalgae utilization, the excess DIC they produced appeared detrimental to their own growth. Moreover, transcriptomic analysis identified several DIC enrichment pathways are evolved in corals to attact the Symbiodiniaceae, including CO2 concentrating mechanisms, respiration, calcification and phosphoenolpyruvate carboxylase. Increased the CO2 dosage in seawater may induce coral symbiosis bleaching. Our findings can deeper reveal on the mechanisms sustaining coral symbiosis, and may help to predict how some corals respond to DIC imbalance under climate changes.

ecology↗

bioRxiv2024

Lightweight taxonomic profiling of long-read sequenced metagenomes with Lemur and Magnet

The advent of long-read sequencing of microbiomes necessitates the development of new taxonomic profilers tailored to long-read shotgun metagenomic datasets. Here, we introduce Lemur and Magnet, a pair of tools optimized for lightweight and accurate taxonomic profiling for long-read shotgun metagenomic datasets. Lemur is a marker-gene-based method that leverages an EM algorithm to reduce false positive calls while preserving true positives; Magnet is a whole-genome read-mapping-based method that provides detailed presence and absence calls for bacterial genomes. We demonstrate that Lemur and Magnet can run in minutes to hours on a laptop with 32 GB of RAM, even for large inputs, a crucial feature given the portability of long-read sequencing machines. Furthermore, the marker gene database used by Lemur is only 4 GB and contains information from over 300,000 RefSeq genomes. Lemur and Magnet are open-source and available at https://github.com/treangenlab/lemur and https://github.com/treangenlab/magnet.

bioinformatics↗

bioRxiv2024

Skeletal Muscle Specific PolG Dysfunction Activates the Integrated Stress Response and Promotes a Cachexia like Phenotype

During mitochondrial damage, information is relayed between the mitochondria and nucleus to coordinate precise responses to preserve cellular health. One such pathway is the mitochondrial integrated stress response (mtISR), which is specifically activated by mitochondrial DNA (mtDNA) damage. However, the causal molecular signals responsible for this activation remain elusive. A gene often associated with mtDNA mutations/deletions is Polg1, which encodes the mitochondrial DNA Polymerase {gamma} (PolG). Here, we describe what is to our knowledge the first conditional muscle specific model of PolG mutation, and demonstrate a rapid development of mitochondrial dysfunction and cachexia in these animals from [~]5 months of age. Detailed molecular profiling of muscles demonstrated robust activation of the mtISR, likely mediated upstream by the HRI/DELE1 stress pathway. This was accompanied by striking alterations to the mitochondrial folate cycle and its metabolites, strongly implying imbalanced folate intermediates as a previously unrecognised pathology driving the mtISR in mitochondrial disease.

physiology↗

bioRxiv2024

Single-nucleus transcriptomic analysis reveals the regulatory circuitry of myofiber XBP1 during regenerative myogenesis

Endoplasmic reticulum (ER) stress-induced unfolded protein response (UPR) are activated in skeletal muscle in multiple conditions. However, the role of the UPR in the regulation of muscle regeneration remains less understood. We demonstrate that gene expression of various markers of the UPR is induced in both myogenic and non-myogenic cells in regenerating muscle. Genetic ablation of XBP1, a downstream target of the IRE1 arm of the UPR, in myofibers attenuates muscle regeneration in adult mice. Single nucleus RNA sequencing (snRNA-seq) analysis showed that deletion of XBP1 in myofibers perturbs proteolytic systems and mitochondrial function in myogenic cells. Trajectory analysis of snRNA-seq dataset showed that XBP1 regulates the abundance of satellite cells and the formation of new myofibers in regenerating muscle. In addition, ablation of XBP1 disrupts the composition of non-myogenic cells in injured muscle microenvironment. Collectively, our study suggests that myofiber XBP1 regulates muscle regeneration through both cell-autonomous and -non-autonomous mechanisms. HIGHLIGHTSO_LIThe UPR is activated in different cell types during muscle regeneration. C_LIO_LITargeted deletion of XBP1 impairs muscle regeneration in adult mice C_LIO_LIMyofiber XBP1 regulates satellite cell dynamics during regenerative myogenesis C_LIO_LIMyofiber XBP1 regulates abundance of non-myogenic cells in regenerating muscle C_LI

cell biology↗

bioRxiv2024

FinaleToolkit: Accelerating Cell-Free DNA Fragmentation Analysis with a High-Speed Computational Toolkit

MotivationCell-free DNA (cfDNA) fragmentation pattern represents a promising non-invasive biomarker for disease diagnosis and prognosis. Numerous fragmentation features, such as end motif and window protection score (WPS), have been characterized in cfDNA genomic sequencing. However, the analytical tools developed in these studies are often not released to the liquid biopsy community or are inefficient for genome-wide analysis in large datasets. ResultsTo address this gap, we have developed FinaleToolkit, a fast and memory-efficient Python package designed to generate comprehensive fragmentation features from large cfDNA genomic sequencing data. For instance, FinaleToolkit can generate genome-wide WPS features from a [~]100X cfDNA whole-genome sequencing (WGS) dataset with over 1 billion fragments in 0.7 hours, offering up to a [~]50-fold increase in processing speed compared to original implementations in the same dataset. We have bench-marked FinaleToolkit against original approaches or implementations where possible, confirming its efficacy. Furthermore, FinaleToolkit enabled the genome-wide analysis of fragmentation patterns over arbitrary genomic intervals, significantly boosting the performance for cancer early detection. Availability and implementationFinaleToolkit is open source and thoroughly documented with both command line interface and Python application programming interface (API) to facilitate its wide-spread adoption and use within the research community: https://github.com/epifluidlab/FinaleToolkit.

bioinformatics↗