Biology subjects

Lu, M.

Publications and source records attributed to Lu, M..

At least 73 records · Page 4Linked to original sources

bioRxiv2024

Conformational trajectory of the HIV-1 fusion peptide during CD4-induced envelope opening

The hydrophobic fusion peptide (FP), a critical component of the HIV-1 entry machinery, is located at the N terminal stretch of the envelope (Env) gp41 subunit1-3. The receptor-binding gp120 subunit of Env forms a heterodimer with gp41 and assembles into a trimer, in which FP is accessible for antibody binding3. Env conformational changes or "opening" that follow receptor binding result in FP relocating to a newly formed interprotomer pocket at the gp41-gp120 interface where it is sterically inaccessible to antibody4. The mechanistic steps connecting the entry-related transition of antibody accessible-to-inaccessible FP configurations remain unresolved. Here, using SOSIP-stabilized Env ectodomains5, we visualized atomic-level details of a functional entry intermediate, where partially open Env was bound to receptor CD4, co-receptor mimetic antibody 17b, and FP-targeting antibody VRC34.01, demonstrating that FP remains antibody accessible despite substantial receptor-induced Env opening. We determined a series of structures delineating stepwise opening of Env from its closed state to a newly resolved intermediate and defining downstream re-organizations of the gp120-gp41 interface that ultimately resulted in FP burial in an antibody-inaccessible configuration. Our studies improve our understanding of HIV-1 entry and provide information on entry-related conformation reorganization of a key site of HIV vulnerability to neutralizing antibody.

microbiology↗

bioRxiv2024

Dissecting reversible and irreversible single cell state transitions from gene regulatory networks

Understanding cell state transitions and their governing regulatory mechanisms remains one of the fundamental questions in biology. We develop a computational method, state transition inference using cross-cell correlations (STICCC), for predicting reversible and irreversible cell state transitions at single-cell resolution by using gene expression data and a set of gene regulatory interactions. The method is inspired by the fact that the gene expression time delays between regulators and targets can be exploited to infer past and future gene expression states. From applications to both simulated and experimental single-cell gene expression data, we show that STICCC-inferred vector fields capture basins of attraction and irreversible fluxes. By connecting regulatory information with systems dynamical behaviors, STICCC reveals how network interactions influence reversible and irreversible state transitions. Compared to existing methods that infer pseudotime and RNA velocity, STICCC provides complementary insights into the gene regulation of cell state transitions.

systems biology↗

bioRxiv2024

HIV-1-envelope trimer transitions from prefusion-closed to CD4-bound-open conformations through an occluded-intermediate state

HIV-1 infection is initiated by the interaction between the gp120 subunit in the envelope (Env) trimer and the cellular receptor CD4 on host cells. This interaction induces substantial structural rearrangement of the Env trimer. Currently, static structural information for prefusion-closed trimers, CD4-bound prefusion-open trimers, and various antibody-bound trimers is available. However, dynamic features between these static states (e.g., transition structures) are not well understood. Here, we investigate the full transition pathway of a site specifically glycosylated Env trimer between prefusion-closed and CD4-bound-open conformations by collective molecular dynamics and single-molecule Forster resonance energy transfer (smFRET). Our investigations reveal and confirm important features of the transition pathway, including movement of variable loops to generate a glycan hole at the trimer apex and formation or rearrangements of -helices and {beta}-strands. Notably, by comparing the transition pathway to known Env-structures, we uncover evidence for a transition intermediate, with four antibodies, Ab1303, Ab1573, b12, and DH851.3, recognizing this intermediate. Each of these four antibodies induce population shifts of Env to occupy a newly observed smFRET state: the "occluded-intermediate" state. We propose this occluded-intermediate state to be both a prevalent state of Env and an on-path conformation between prefusion-closed and CD4-bound-open states, previously overlooked in smFRET analyses.

bioinformatics↗

bioRxiv2024

A host enzyme reduces non-alcoholic fatty liver disease by inactivating intestinal lipopolysaccharide

The incidence of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) has been increasing world-wide. Since gut-derived bacterial lipopolysaccharides (LPS) can travel via the portal vein to the liver and play an important role in producing hepatic pathology, it seemed possible that (1) LPS stimulates hepatic cells to accumulate lipid, and (2) inactivating LPS can be preventive. Acyloxyacyl hydrolase (AOAH), the eukaryotic lipase that inactivates LPS and oxidized phospholipids, is produced in the intestine, liver, and other organs. We fed mice either normal chow or a high-fat diet for 28 weeks and found that Aoah-/- mice accumulated more hepatic lipid than did Aoah+/+ mice. In young mice, before increased hepatic fat accumulation was observed, Aoah-/-mouse livers increased their abundance of Sterol Regulatory Element-Binding Protein 1 (SREBP1) and the expression of its target genes that promote fatty acid synthesis. Aoah-/- mice also increased hepatic expression of CD36 and Fabp3, which mediate fatty acid uptake, and decreased expression of fatty acid oxidation-related genes Acot2 and Ppar-. Our results provide evidence that increasing AOAH abundance in the gut, bloodstream and/or liver may be an effective strategy for preventing or treating MASLD.

immunology↗

bioRxiv2024

Calorie Restriction Induces Degeneration of Neurons with Mitochondrial DNA Depletion by Altering ER-Mitochondria Calcium Transfer

Mitochondrial DNA (mtDNA) mutations and/or depletion are implicated in epilepsy and many neurodegenerative diseases. However, systematic investigation into how mtDNA alterations relate to epilepsy and neural degeneration is needed. Here, we established a mouse model where in mtDNA depletion induced by Herpes Simplex Virus Type 1 (HSV-1) protein-UL12.5 in the brain led to an epileptic phenotype characterized by abnormal electroencephalography (EEG) patterns and increased neural excitability in hippocampus. We also found that UL12.5 mediated mtDNA depletion in neurons in vitro (rho-) causes epilepsy-like abnormal EEG. Caloric restriction (CR) is a strategy proven to reduce epileptic activity, however CR mimetic 2-deoxy-D-glucose (2-DG), induced degeneration in mtDNA depleted neurons. Mechanistically, mtDNA depletion increased mitochondria-endoplasmic reticulum (ER) contacts, facilitating CR-induced mitochondrial calcium overload. Rho- neurons did not show changes in mitochondrial motility or membrane potential. Our study revealed an unexpected axis of mtDNA depletion, ER-mitochondrial contacts, and calcium overload in the rho- neuron model. This is the first description of animal and neuronal models of mitochondrial epilepsy. Our findings with these models suggest that CR may not be a viable clinical intervention in patients with mtDNA depletion.

cell biology↗

bioRxiv2024

Ancestral SARS-CoV-2 immune imprinting persists on RBD but not NTD after sequential Omicron infections

Whether Omicron exposures could overcome ancestral SARS-CoV-2 immune imprinting remains controversial. Here we analyzed B cell responses evoked by sequential Omicron infections in vaccinated and unvaccinated individuals. Plasma neutralizing antibody titers against ancestral SARS-CoV-2 and variants indicate that immune imprinting is not consistently induced by inactivated or recombinant protein vaccines. However, once induced, immune imprinting is not countered by successive Omicron challenges. We compared binding specificities, neutralizing capacities, developing origins and targeting epitopes of monoclonal antibodies from individuals with or without immune imprinting. Although receptor-binding domain (RBD) and N-terminal domain (NTD) of spike are both primary targets for neutralizing antibodies, immune imprinting only shapes antibody responses to RBD by impeding the production of Omicron-specific neutralizing antibodies while facilitating the development of broadly neutralizing antibodies. We propose that immune imprinting can be either neglected by NTD-based vaccines to induce variant-specific antibodies or leveraged by RBD-based vaccines to induce broadly neutralizing antibodies.

immunology↗

bioRxiv2024

Exploring Integrin α5β1 as a Potential Therapeutic Target for Pulmonary Arterial Hypertension: Insights from Comprehensive Multicenter Preclinical Studies

Pulmonary arterial hypertension (PAH) is characterized by obliterative vascular remodeling of the small pulmonary arteries (PA) and progressive increase in pulmonary vascular resistance (PVR) leading to right ventricular (RV) failure. Although several drugs are approved for the treatment of PAH, mortality remains high. Accumulating evidence supports a pathological function of integrins in vessel remodeling, which are gaining renewed interest as drug targets. However, their role in PAH remains largely unexplored. We found that the arginine-glycine-aspartate (RGD)-binding integrin 5{beta}1 is upregulated in PA endothelial cells (PAEC) and PA smooth muscle cells (PASMC) from PAH patients and remodeled PAs from animal models. Blockade of the integrin 5{beta}1 or depletion of the 5 subunit resulted in mitotic defects and inhibition of the pro-proliferative and apoptosis-resistant phenotype of PAH cells. Using a novel small molecule integrin inhibitor and neutralizing antibodies, we demonstrated that 5{beta}1 integrin blockade attenuates pulmonary vascular remodeling and improves hemodynamics and RV function in multiple preclinical models. Our results provide converging evidence to consider 5{beta}1 integrin inhibition as a promising therapy for pulmonary hypertension. One sentence summaryThe 5{beta}1 integrin plays a crucial role in pulmonary vascular remodeling.

pathology↗

bioRxiv2024

Amd1-skp2 cascade regulates hepatocyte proliferation during liver growth and hepatocellular carcinoma development in zebrafish

Rapid hepatocyte proliferation is a common characteristic of liver growth in early liver development and hepatocellular carcinoma (HCC). Clarifying the mechanism how liver growth is regulated in development would benefit studying HCC progress. Although many genes have been reported to be involved in liver growth during early development, the mechanism underlying liver growth is far from being elucidated. Here we found that the liver undergoes rapid growth from 2dpf to 5dpf in zebrafish. Comparing the transcriptome for different staged hepatocytes identified 813 hepatocyte enriched genes at 3 dpf. Among them, S-adenosylmethionine decarboxylase proenzyme (AMD1) had not been previously reported to be involved in liver development. Our study further confirmed that amd1 was highly enriched in hepatocytes during liver rapid growth and that amd1 mutation inhibited liver growth mainly by repressing hepatocyte proliferation. Mechanistically, amd1 loss of function downregulated the expression of skp2, and skp2 is required for amd1 to regulate hepatocyte proliferation. Furthermore, the role of Amd1-Skp2 cascade in regulating hepatocyte proliferation was also conserved in a zebrafish HCC model. In conclusion, our study systematically identified some uncharacterized genes possibly being involved in regulating liver growth during zebrafish development, and revealed the role of amd1-skp2 cascade in regulating hepatocyte proliferation during liver growth and HCC progression. This work also provided a database which would benefit elucidating the mechanism how hepatocyte proliferation is regulated during liver growth and HCC progress.

developmental biology↗

bioRxiv2024

Clostridium ablates tumors by degrading collagen mesh andinducing ferroptosis

The supportive role of extracellular matrix in tumor growth and the drug resistance of tumor cells stand the major challenges in treating cancer. Here, we report the discovery of an oncolytic Clostridium strain, named RJ-1, which simultaneously expresses collagenases and produces iron-containing particles through intrabacterial mineralization. The secreted collagenases degrade pre-existing collagen mesh and show a collagen concentration-dependent degradation feature. Iron-containing particles released from RJ-1 by autolysis generate ferrous ions in the lysosomal acid environment following cell uptake and subsequently induce ferroptosis via the Fenton reaction. Due to selective germination in tumor sites, systemic administration of RJ-1 spores synchronously destructs dense tumor extracellular matrix and causes non-apoptotic tumor cell death. In collagen-dense tumor-bearing mice, a single intravenous injection achieves a favorable tolerance and rapid oncolysis of giant tumors with a size of [~]1000 mm3. This work finds a dual collagenase-expressing and iron-concentrating bacterium, proposing an alternative strategy to combat tumors.

microbiology↗

bioRxiv2024

Bone morphogenetic protein (BMP) signaling determines neuroblastoma cell fate and sensitivity to retinoic acid.

Retinoic acid (RA) is a standard-of-care neuroblastoma drug thought to be effective by inducing differentiation. Curiously, RA has little effect on primary human tumors during upfront treatment but can eliminate neuroblastoma cells from the bone marrow during post-chemo consolidation therapy--a discrepancy that has never been explained. To investigate this, we treated a large cohort of neuroblastoma cell lines with RA and observed that the most RA-sensitive cells predominantly undergo apoptosis or senescence, rather than differentiation. We conducted genome-wide CRISPR knockout screens under RA treatment, which identified BMP signaling as controlling the apoptosis/senescence vs differentiation cell fate decision and determining RAs overall potency. We then discovered that BMP signaling activity is markedly higher in neuroblastoma patient samples at bone marrow metastatic sites, providing a plausible explanation for RAs ability to clear neuroblastoma cells specifically from the bone marrow, seemingly mimicking interactions between BMP and RA during normal development.

cancer biology↗

bioRxiv2024

Genetic architecture underlying response to the fungal pathogen Dothistroma septosporum in lodgepole pine, jack pine, and their hybrids

In recent decades, Dothistroma needle blight (DNB), a pine tree disease caused by the fungal pathogen Dothistroma septosporum, has severely damaged lodgepole pine (Pinus contorta Dougl. ex. Loud.) in British Columbia, Canada, and raised health concerns for jack pine (Pinus banksiana Lamb.). The pathogen has already shown signs of host shift eastward to the hybrid populations between lodgepole pine and jack pine (Pinus contorta x P. banksiana), and possibly into pure jack pine. However, we have little knowledge about mechanisms of resistance to D. septosporum, especially the underlying genetic basis of variation in pines. In this study, we conducted controlled inoculations to induce infection by D. septosporum and performed a genome-wide case-control association study with pooled sequencing (pool-seq) data to dissect the genetic architecture underlying response in lodgepole pine, jack pine, and their hybrids. We identified candidate genes associated with D. septosporum response in lodgepole pine and in hybrid samples. We also assessed genetic structure in hybrid populations and inferred how introgression may affect the distribution of genetic variation involved in D. septosporum response in the studied samples. These results can be used to develop genomic tools to evaluate DNB risk, guide forest management strategies, and potentially select for resistant genotypes.

plant biology↗

bioRxiv2024

Establishing comprehensive quaternary structural proteomes from genome sequence

A critical body of knowledge has developed through advances in protein microscopy, protein-fold modeling, structural biology software, availability of sequenced bacterial genomes, large-scale mutation databases, and genome-scale models. Based on these recent advances, we develop a computational framework that; i) identifies the oligomeric structural proteome encoded by an organisms genome from available structural resources; ii) maps multi-strain alleleomic variation, resulting in the structural proteome for a species; and iii) calculates the 3D orientation of proteins across subcellular compartments with residue-level precision. Using the platform, we; iv) compute the quaternary E. coli K-12 MG1655 structural proteome; v) use a dataset of 12,000 mutations to build Random Forest classifiers that can predict the severity of mutations; and, in combination with a genome-scale model that computes proteome allocation, vi) obtain the spatial allocation of the E. coli proteome. Thus, in conjunction with relevant datasets and increasingly accurate computational models, we can now annotate quaternary structural proteomes, at genome-scale, to obtain a molecular-level understanding of whole-cell functions. SignificanceAdvancements in experimental and computational methods have revealed the shapes of multi-subunit proteins. The absence of a unified platform that maps actionable datatypes onto these increasingly accurate structures creates a barrier to structural analyses, especially at the genome-scale. Here, we describe QSPACE, a computational annotation platform that evaluates existing resources to identify the best-available structure for each protein in a users query, maps the 3D location of actionable datatypes (e.g., active sites, published mutations) onto the selected structures, and uses third-party APIs to determine the subcellular compartment of all amino acids of a protein. As proof-of-concept, we deployed QSPACE to generate the quaternary structural proteome of E. coli MG1655 and demonstrate two use-cases involving large-scale mutant analysis and genome-scale modelling.

bioinformatics↗

bioRxiv2024

PAK6 rescues pathogenic LRRK2-mediated ciliogenesis and centrosomal cohesion defects in a mutation-specific manner

P21 activated kinase 6 (PAK6) is a serine-threonine kinase with physiological expression enriched in the brain and overexpressed in a number of human tumors. While the role of PAK6 in cancer cells has been extensively investigated, the physiological function of the kinase in the context of brain cells is poorly understood. Our previous work uncovered a link between PAK6 and the Parkinsons disease (PD)-associated kinase LRRK2, with PAK6 controlling LRRK2 activity and subcellular localization via phosphorylation of 14-3-3 proteins. Here, to gain more insights into PAK6 physiological function, we performed protein-protein interaction arrays and identified a subgroup of PAK6 binders related to ciliogenesis. We confirmed that endogenous PAK6 localizes at both the centrosome and the cilium, and positively regulates ciliogenesis not only in tumor cells but also in neurons and astrocytes. Strikingly, PAK6 rescues ciliogenesis and centrosomal cohesion defects associated with the G2019S but not the R1441C LRRK2 PD mutation. Since PAK6 binds LRRK2 via its GTPase/Roc-COR domain and the R1441C mutation is located in the Roc domain, we used microscale thermophoresis and AlphaFold2-based computational analysis to demonstrate that PD mutations in LRRK2 affecting the Roc-COR structure substantially decrease PAK6 affinity, providing a rationale for the differential protective effect of PAK6 toward the distinct forms of mutant LRRK2. Altogether, our study discloses a novel role of PAK6 in ciliogenesis and points to PAK6 as the first LRRK2 modifier with PD mutation-specificity.

neuroscience↗

bioRxiv2024

Ca2+-independent ZmCPK2 is inhibited by Ca2+-dependent ZmCPK17 during drought response in maize

Calcium oscillations are induced by different stresses. Calcium-dependent protein kinases (CDPKs/CPKs) are one major group of the plant calcium decoders that are involved in various processes including drought response. Some CPKs are calcium-independent. Here, we identified ZmCPK2 as a negative regulator of drought resistance by screening an overexpression transgenic maize pool. We found that ZmCPK2 does not bind calcium, and its activity is modulated likely in an oscillation manner during short time ABA treatment. Interestingly, ZmCPK2 interacts with and is inhibited by calcium-dependent ZmCPK17, a positive regulator of drought resistance, which is activated by ABA. ZmCPK17 activity exhibits opposite patterns relative to ZmCPK2 under ABA treatment, and could prevent the nuclear localization of ZmCPK2 when co-expressed. ZmCPK2 interacts with and phosphorylates ZmYAB15, a negative transcriptional factor for drought resistance. Our results suggest that drought stress-induced Ca2+ can be decoded by corresponding CPK17 likely in an oscillation manner, thereby promoting plant adaptation to water deficit.

molecular biology↗

bioRxiv2024

Conditional c-MYC activation in catecholaminergic cells drives distinct neuroendocrine tumors: neuroblastoma vs somatostatinoma

The MYC proto-oncogenes (c-MYC, MYCN, MYCL) are among the most deregulated oncogenic drivers in human malignancies including high-risk neuroblastoma, 50% of which are MYCN-amplified. Genetically engineered mouse models (GEMMs) based on the MYCN transgene have greatly expanded the understanding of neuroblastoma biology and are powerful tools for testing new therapies. However, a lack of c-MYC-driven GEMMs has hampered the ability to better understand mechanisms of neuroblastoma oncogenesis and therapy development given that c-MYC is also an important driver of many high-risk neuroblastomas. In this study, we report two transgenic murine neuroendocrine models driven by conditional c-MYC induction in tyrosine hydroxylase (Th) and dopamine {beta}-hydroxylase (Dbh)-expressing cells. c-MYC induction in Th-expressing cells leads to a preponderance of Pdx1+ somatostatinomas, a type of pancreatic neuroendocrine tumor (PNET), resembling human somatostatinoma with highly expressed gene signatures of {delta} cells and potassium channels. In contrast, c-MYC induction in Dbh-expressing cells leads to onset of neuroblastomas, showing a better transforming capacity than MYCN in a comparable C57BL/6 genetic background. The c-MYC murine neuroblastoma tumors recapitulate the pathologic and genetic features of human neuroblastoma, express GD2, and respond to anti-GD2 immunotherapy. This model also responds to DFMO, an FDA-approved inhibitor targeting ODC1, which is a known MYC transcriptional target. Thus, establishing c-MYC-overexpressing GEMMs resulted in different but related tumor types depending on the targeted cell and provide useful tools for testing immunotherapies and targeted therapies for these diseases.

cancer biology↗

bioRxiv2024

Resting natural killer cells promote the progress of colon cancer liver metastasis by elevating tumor-derived sSCF

PurposeThe abundance and biological contribution of Natural killer (NK) cells in cancer are controversial. Here, we aim to uncover clinical relevance and cellular roles of NK cells in colon cancer liver metastasis (CCLM) MethodsWe integrated single-cell RNA sequencing, spatial transcriptomics, and bulk RNA-sequencing datasets to investigate NK cells biological properties and functions in the microenvironment of primary and liver metastatic tumors. Results were validated through an in vitro co-culture experiment based on bioinformatics analysis. ResultsWe used single-cell RNA sequencing and spatial transcriptomics to map the immune cellular landscape of colon cancer and well-matched liver metastatic cancer. We discovered that GZMK+ resting NK cells increased significantly in tumor tissues and were enriched in the tumor regions of both diseases. After combining bulk RNA and clinical data, we observed that these NK cell subsets contributed to a worse prognosis. Meanwhile, KIR2DL4+ activated NK cells exhibited the opposite position and relevance. Pseudotime cell trajectory analysis revealed the evolution of activated to resting NK cells. In vitro experiments further confirmed that tumor-cell-co-cultured NK cells exhibited a decidual-like status, as evidenced by remarkable increasing CD9 expression. Functional experiments finally revealed that NK cells exhibited tumor-activating characteristics by promoting the dissociation of SCF (stem cell factor) on the tumor cells membrane depending on cell-to-cell interaction, as the supernatant of the co-culture system enhanced tumor progression. ConclusionTogether, our findings revealed a population of protumorigenic NK cells that may be exploited for novel therapeutic strategies to improve therapeutic outcomes for patients with CCLM.

immunology↗

bioRxiv2024

Graphene microelectrode arrays, 4D structured illumination microscopy, and a machine learning-based spike sorting algorithm permit the analysis of ultrastructural neuronal changes during neuronal signalling in a model of Niemann-Pick disease type C

Simultaneously recording network activity and ultrastructural changes of the synapse is essential for advancing our understanding of the basis of neuronal functions. However, the rapid millisecond-scale fluctuations in neuronal activity and the subtle sub-diffraction resolution changes of synaptic morphology pose significant challenges to this endeavour. Here, we use graphene microelectrode arrays (G-MEAs) to address these challenges, as they are compatible with high spatial resolution imaging across various scales as well as high temporal resolution electrophysiological recordings. Furthermore, alongside G-MEAs, we deploy an easy-to-implement machine learning-based algorithm to efficiently process the large datasets collected from MEA recordings. We demonstrate that the combined use of G-MEAs, machine learning (ML)-based spike analysis, and four-dimensional (4D) structured illumination microscopy (SIM) enables the monitoring of the impact of disease progression on hippocampal neurons which have been treated with an intracellular cholesterol transport inhibitor mimicking Niemann-Pick disease type C (NPC) and show that synaptic boutons, compared to untreated controls, significantly increase in size, which leads to a loss in neuronal signalling capacity.

neuroscience↗

bioRxiv2023

Enhancing Hi-C contact matrices for loop detection with Capricorn, a multi-view diffusion model

High-resolution Hi-C contact matrices reveal the detailed three-dimensional architecture of the genome, but high-coverage experimental Hi-C data are expensive to generate. On the other hand, chromatin structure analyses struggle with extremely sparse contact matrices. To address this problem, computational methods to enhance low-coverage contact matrices have been developed, but existing methods are largely based on resolution enhancement methods for natural images and hence often employ models that do not distinguish between biologically meaningful contacts, such as loops, and other stochastic contacts. We present Capricorn, a machine learning model for Hi-C resolution enhancement that incorporates small-scale chromatin features as additional views of the input Hi-C contact matrix and leverages a diffusion probability model backbone to generate a high-coverage matrix. We show that Capricorn outperforms the state of the art in a cross-cell-line setting, improving on existing methods by 17.8% in mean squared error and 22.9% in F1 score for chromatin loop identification from the generated high-coverage data. We also demonstrate that Capricorn performs well in the cross-chromosome setting and cross-chromosome, cross-cell-line setting, improving the downstream loop F1 score by 15.7% relative to existing methods. We further show that our multi-view idea can also be used to improve several existing methods, Hi-CARN and HiCNN, indicating the wide applicability of this approach. Finally, we use DNA sequence to validate discovered loops and find that the fraction of CTCF-supported loops from Capricorn is similar to those identified from the high-coverage data. Capricorn is a powerful Hi-C resolution enhancement method that enables scientists to find chromatin features that cannot be identified in the low-coverage contact matrix. Implementation of Capricorn and source code for reproducing all figures in this paper are available at https://github.com/CHNFTQ/Capricorn.

bioinformatics↗