Biology subjects

Chen, X.

Publications and source records attributed to Chen, X..

At least 1,405 records · Page 78Linked to original sources

bioRxiv2020

Improved subspecies identification in clinical Mycobacterium abscessus complex isolates using whole genome sequence

Mycobacterium abscessus complex, which is frequently reported causing a variety of skin and soft tissues diseases in humans, is composed of three subspecies, namely M. abscessus subsp. abscessus, M. abscessus subsp. massiliense and M. abscessus subsp. bolletii. Currently, the differentiation of these three subspecies in clinical isolates still largely depend on single gene identification methods like the genes namely hsp65, 16s with a limited accuracy. This study confirmed the limitations of the single gene based method in the subspecies identification. We performed a comprehensive analysis of MABC genomes in the NCBI database and tried to build an accurate and user-friendly identify method. Here, we describe an improved assay for Mycobacterium abscessus complex fast identification using WGS data, based on the identities of rpoB, erm(41) and rpls. Comprehensive analysis has been performed to compare our software results with the traditional method. The result showed that the method built-in this study could 100% identification the subspecies for the Mycobacterium abscessus complex in the public genome database (893 genomes from NCBI database and 6 clinical isolates from this study). Because this software can be easily integrated into a routine workflow to quickly and precisely provide subspecies-level identification and discrimination MABC different subspecies in clinical isolates by WGS. This assay will facilitate accurate molecular identification of species from the MABC complex in a variety of clinical specimens and diagnostic contexts.

microbiology↗

bioRxiv2019

Single cell transcriptome of CD8+ T cells in multiple cancers reveals comprehensive exhaustion associated mechanisms

T cell exhaustion is one of the main reasons of tumor immune escape. Using single cell transcriptome data of CD8+ T cells in multiple cancers, we identified different cell types, in which Pre_exhaust and exhausted T cells participated in negative regulation of immune system process. By analyzing the co-expression network patterns and differentially expressed genes of Pre_exhaust, exhausted and effector T cells, we identified 35 genes related to T cell exhaustion, which high GSVA scores were associated with significantly poor prognosis in various cancers. In the differentially expressed genes, RGS1 showed the greatest fold change in Pre_exhaust and exhausted cells of three cancers compared with effector T cells, and high expression of RGS1 was also associated with poor prognosis in various cancers. Additionally, RGS1 protein was upregulated significantly in tumor tissues in the immunohistochemistry verification. Furthermore, RGS1 displayed positive correlation with the 35 genes, especially highly correlated with PDCD1, CTLA4, HAVCR2 and TNFRSF9 in CD8+ T cells and cancer tissues, indicating important roles of RGS1 in CD8+ T cell exhaustion. Considering the GTP-hydrolysis activity of RGS1 and significantly high mRNA and protein expression in cancer tissues, we speculated that RGS1 potentially mediate the T cell retention to lead to the persistent antigen stimulation, resulting in T cell exhaustion. In conclusion, our findings suggest that RGS1 is a new marker and promoting factor for CD8+ T cell exhaustion, and provide theoretical basis for research and immunotherapy of exhausted cells.

cancer biology↗

bioRxiv2019

Developing a DeSipher method for conformational change detection of membrane receptor complex at residue resolution

While one dimensional 1H nuclear magnetic resonance (1D 1H-NMR) spectroscopy is one of the most important and convenient method for measuring conformation change in biomacromolecules, characterization of protein dynamics in large membrane protein complexes by 1D 1H-NMR remains challenging, due to the difficulty of spectra assignment, low signal-to-noise ratio (S/N) and the need for large amount of protein. Here we report the site-specific incorporation of 4-trimethylsilyl phenylalanine (TMSiPhe) into proteins, through genetic code expansion in Escherichia coli cells, and the measurement of multiple conformational states in membrane protein complex by 1D 1H-NMR. The unique up-field 1H-NMR chemical shift of TMSiPhe, highly efficient and specific incorporation of TMSiPhe enabled facile assignment of the TMSiPhe 1H-NMR signal, and characterization of multiple conformational state in a 150 kilodalton (kD) membrane protein complex, using only 5 M of protein and 20 min spectra accumulation time. This highly efficient and convenient methods should be broadly applicable for the investigation of dynamic conformation change of protein complexes.

biochemistry↗

bioRxiv2019

CDE-1 suppresses the production of risiRNA by coupling polyuridylation and degradation of 26S rRNA

Antisense ribosomal siRNAs (risiRNAs) downregulate pre-rRNAs through the nuclear RNAi pathway in Caenorhabditis elegans. However, the biogenesis and regulation of risiRNAs remain obscure. Previously, we showed that 26S rRNAs are uridylated at the 3-ends by an unknown terminal polyuridylation polymerase before the rRNAs are degraded by a 3 to 5 exoribonuclease SUSI-1(ceDIS3L2). There are three polyuridylation polymerases, CDE-1, PUP-2, and PUP-3, in C. elegans. Here, we found that CDE-1 is specifically involved in suppressing risiRNA production. CDE-1 localizes to perinuclear granules in the germline and uridylates both Argonaute-associated 22G-RNAs and 26S rRNAs at the 3-ends. Immunoprecipitation followed by mass spectrometry (IP-MS) revealed that CDE-1 interacts with SUSI-1(ceDIS3L2). Consistent with those results, both CDE-1 and SUSI-1(ceDIS3L2) are required for the inheritance of RNAi. Therefore, this work identified a rRNA surveillance machinery of rRNAs that couples terminal polyuridylation and degradation.

molecular biology↗

bioRxiv2019

Dopaminergic Neurodegeneration Induced by Parkinson's Disease-Linked G2019S LRRK2 is Dependent on Kinase and GTPase Activity

AO_SCPLOWBSTRACTC_SCPLOWMutations in the leucine-rich repeat kinase 2 (LRRK2) gene cause late-onset, autosomal dominant familial Parkinsons disease (PD) and represent the most common known cause of PD. LRRK2 can function as both a protein kinase and GTPase and PD-linked mutations are known to influence both of these enzymatic activities. While PD-linked LRRK2 mutations can commonly induce neuronal damage and toxicity in cellular models, the mechanisms underlying these pathogenic effects remain uncertain. Rodent models based upon familial LRRK2 mutations often lack the hallmark features of PD and robust neurodegenerative phenotypes in general. Here, we develop a robust pre-clinical model of PD in adult rats induced by the brain delivery of recombinant adenoviral vectors with neuronal-specific expression of full-length human LRRK2 harboring the most common G2019S mutation. In this model, G2019S LRRK2 induces the robust degeneration of substantia nigra dopaminergic neurons, a pathological hallmark of PD. Introduction of a stable kinase-inactive mutation or in-diet dosing with the selective kinase inhibitor, PF-360, attenuates neurodegeneration induced by G2019S LRRK2. Neuroprotection provided by pharmacological kinase inhibition is mediated by an unusual mechanism involving the selective and robust destabilization of human LRRK2 protein in the rat brain relative to endogenous LRRK2. Our study further demonstrates that dopaminergic neurodegeneration induced by G2019S LRRK2 critically requires normal GTPase activity. The introduction of hypothesis-testing mutations that increase GTP hydrolysis or impair GTP binding activity provide neuroprotection against G2019S LRRK2 via distinct mechanisms. Taken together, our data demonstrate that G2019S LRRK2 induces neurodegeneration in vivo via a mechanism that is dependent on kinase and GTPase activity. Our study provides a robust rodent model of LRRK2-linked PD and nominates kinase inhibition and modulation of GTPase activity as promising disease-modifying therapeutic targets.

neuroscience↗

bioRxiv2019

Genetic characterization of Streptococcus equi subspecies zooepidemicus associated with high swine mortality in United States

High mortality events due to Streptococcus equi subspecies zooepidemicus (S. zooepidemicus) in swine have not previously been reported in the United States. In September and October 2019, outbreaks with swine mortality up to 50% due to S. zooepidemicus septicemia were reported in Ohio and Tennessee. Genomic epidemiological analysis revealed that the eight outbreak isolates were clustered together with ATCC 36246, a Chinese strain caused outbreaks with high mortality, also closely related to three isolates from human cases from Virginia, but significantly different from an outbreak-unrelated swine isolate from Arizona and most isolates from other animal species. Comparative genomic analysis on two outbreak isolates and another outbreak-unrelated isolate identified several genomic islands and virulence genes specifically in the outbreak isolates only, which are likely associated with the high mortality observed in the swine population. These findings have implications for understanding, tracking, and possibly preventing diseases caused by S. zooepidemicus in swine.

microbiology↗

bioRxiv2019

Recombinant HcGAPDH Protein Expressed on Probiotic Bacillus subtilis Spores Protects Sheep from Haemonchus contortus Infection by Inducing both Humoral and Cell-mediated Responses

Probiotic Bacillales have been shown effective in controlling pathogens. In particular, live probiotic bacteria are thought to improve the composition of gastrointestinal microbiota, and to reduce pathogen colonization. However, how probiotics regulate immune responses and protect the host from parasitic infection remains largely unknown. In this study, we investigated whether Bacillales can be used against Haemonchus contortus, a parasitic nematode that infects small ruminants in sheep and goats worldwide. Using 16S ribosomal RNA sequencing, we found that Bacillales was highly depleted in the abomasal microbiota of sheep infected with H. contortus. We constructed a recombinant Bacillus subtilis strain (rBSCotB-HcG) that express glyceraldehyde-3-phosphate dehydrogenase of H. contortus (HcGAPDH) on its spore surface. However, mice orally administrated with the rBSCotB-HcG strain showed strong Th1-dominated immune responses; and sheep administrated per os with rBSCotB-HcG showed increased proliferation of peripheral blood mononuclear cells, elevated anti-HcGAPDH IgG levels in sera, and higher anti-HcGAPDH sIgA levels in intestinal mucus. In addition, treatment of H. contortus infected sheep with rBSCotB-HcG (Hc+rBSCotB-HcG) promoted the abundance of probiotic species in the abomasal microbiota; it also improved the average weight gain of the sheep by 27.7%. These Hc+rBSCotB-HcG sheep have reduced number of eggs per gram of feces (by 84.1%) and worm burdens (by 71.5%), with alleviated abomasal damage by H. contortus. Collectively, our data demonstrate the protective roles of CotB-HcGAPDH-expressing B. subtilis spores against H. contortus infection, suggesting a potential value of using this probiotic-based strategy in controlling parasitic nematodes of socioeconomic importance. ImportanceSequencing of the infected sheep s stomach flora revealed potential probiotics that could control H. contortus infection, and further genetically engineered recombinant probiotic spores expressing parasite protein, and validated their good immunogenicity in a mouse model. In the sheep infection model, the recombinant probiotics have proven to be effective against parasite infections.

microbiology↗

bioRxiv2019

Pharmacological inhibition of acid sensing ion channel 1a protects the heart from ischemia-reperfusion injury

The proton-gated acid-sensing ion channel 1a (ASIC1a) is implicated in the injury response to cerebral ischemia but little is known about its role in cardiac ischemia. We provide genetic evidence that ASIC1a is involved in myocardial ischemia-reperfusion injury (IRI) and show that pharmacological inhibition of ASIC1a yields robust cardioprotection in rodent and human models of cardiac ischemia, resulting in improved post-IRI cardiac viability and function. Consistent with a key role for ASIC1a in cardiac ischemia, we show that polymorphisms in the ASIC1 genetic locus are strongly associated with myocardial infarction. Collectively, our data provide compelling evidence that ASIC1a is a key target for cardioprotective drugs to reduce the burden of disease associated with myocardial ischemia.

physiology↗

bioRxiv2019

LncRNA and predictive model to improve the diagnosis of clinically diagnosed pulmonary tuberculosis

BackgroundClinically diagnosed pulmonary tuberculosis (PTB) patients lack Mycobacterium tuberculosis (MTB) microbiologic evidence, and misdiagnosis or delayed diagnosis often occurs as a consequence. We investigated the potential of lncRNAs and corresponding predictive models to diagnose these patients. MethodsWe enrolled 1372 subjects, including clinically diagnosed PTB patients, non-TB disease controls and healthy controls, in three cohorts (Screening, Selection and Validation). Candidate lncRNAs differentially expressed in blood samples of the PTB and healthy control groups were identified by microarray and qRT-PCR in the Screening Cohort. Logistic regression models were developed using lncRNAs and/or electronic health records (EHRs) from clinically diagnosed PTB patients and non-TB disease controls in the Selection Cohort. These models were evaluated by AUC and decision curve analysis, and the optimal model was presented as a Web-based nomogram, which was evaluated in the Validation Cohort. The biological function of lncRNAs was interrogated using ELISA, lactate dehydrogenase release analysis and flow cytometry. ResultsThree differentially expressed lncRNAs (ENST00000497872, n333737, n335265) were identified. The optimal model (i.e., nomogram) incorporated these three lncRNAs and six EHR variables (age, hemoglobin, weight loss, low-grade fever, CT calcification and TB-IGRA). The nomogram showed an AUC of 0.89, sensitivity of 0.86 and specificity of 0.82 in the Validation Cohort, which demonstrated better discrimination and clinical net benefit than the EHR model. ENST00000497872 may regulate inflammatory cytokine production, cell death and apoptosis during MTB infection. ConclusionsLncRNAs and the user-friendly nomogram could facilitate the early identification of PTB cases among suspected patients with negative MTB microbiologic evidence.

molecular biology↗

bioRxiv2019

The HMGB1-RAGE axis modulates the growth of autophagy-deficient hepatic tumors

Autophagy is an intracellular lysosomal degradative pathway important for tumor surveillance. Autophagy deficiency can lead to tumorigenesis. Autophagy is also known to be important for the aggressive growth of tumors, yet the mechanism that sustains the growth of autophagy-deficient tumors is not known. We previously reported that progression of hepatic tumors developed in autophagy-deficient livers required high mobility group box 1 (HMGB1) that is released from autophagy-deficient hepatocytes. However, the mechanism by which HMGB1 promotes hepatic tumorigenesis is not understood. In this study we examined the pathological features of the hepatic tumors and the mechanism of HMGB1-mediated tumorigenesis using liver-specific autophagy-deficient (Atg7-/-) and Atg7-/-/Hmgb1-/- mice. We found that in Atg7-/- mice the tumors cells were still deficient in autophagy and could also release HMGB1. Histological analysis using cell-specific markers suggested that fibroblast and ductular cells were present only outside the tumor whereas macrophages were present both inside and outside the tumor. Genetic deletion of HMGB1 or one of its receptors, receptor for advanced glycated end product (Rage), retarded liver tumor development. In addition, we found that expression of RAGE was only on ductual cells and Kupffers cells but not on hepatoctyes, which suggested that HMGB1 might promote hepatic tumor growth through a paracrine mode that altered the tumor microenvironment. Furthermore, HMGB1 and RAGE enhanced the proliferation capability of the autophagy-deficient hepatocytes and tumors. Finally, RNAseq analysis of the tumors indicated that HMGB1 induced a much broad changes in tumors. In particular, genes related to mitochondrial structures or functions were enriched among those differentially expressed in tumors in the presence or absence of HMGB1, revealing a potential key role of mitochondria in sustaining the growth of autophagy-deficient liver tumors via HMGB1 stimulation.

cancer biology↗

bioRxiv2019

SIRT2-knockdown Rescues GARS-induced Charcot-Marie-Tooth Neuropathy

Charcot-Marie-Tooth disease is the most common inherited peripheral neuropathy. Dominant mutations in glycyl-tRNA synthetase (GARS) gene cause peripheral nerve degeneration and lead to CMT disease type 2D. Mutations in GARS (GARSCMT2D) show partial loss-of-function features, suggesting that tRNA-charging deficits play a role in disease pathogenesis, but the underlying mechanisms are not fully understood. In this study we report that wild-type GARS tightly binds the NAD+-dependent deacetylase SIRT2 and inhibits its deacetylation activity, resulting in the hyperacetylated -tubulin, the major substrate of SIRT2. Previous studies showed that acetylation of -tubulin protects microtubules from mechanical breakage and keep axonal transportation. However, CMT2D mutations in GARS can not inhibit SIRT2 deacetylation, which leads to decrease acetylated -tubulin and severe axonal transport deficits. Genetic reduction of SIRT2 in the Drosophila model rescues the GARS-induced axonal CMT neuropathy and extends the life span. Our findings demonstrate the pathogenic role of SIRT2-dependent -tubulin deacetylation in mutant GARS-induced neuropathies and provide new perspectives for targeting SIRT2 as a potential therapy against hereditary axonopathies.

cell biology↗

bioRxiv2019

Deoxynivalenol Promotes Porcine Epidemic Diarrhea Virus Infection and Aggravates Gut Barrier Injury

Porcine epidemic diarrhea virus (PEDV) is a highly contagious pathogenic virus that causes severe diarrhea and dehydration in pigs of all ages. Deoxynivalenol (DON), the most abundant trichothecene in food and feed, causes vomit and diarrhea in animals and human. However, whether DON exposure could affect PEDV infection remains unknown. Herein, we investigated the impacts of DON on entry and replication of PEDV, morbidity situation of piglets and the mechanisms involved. In vivo, twenty-seven piglets infected naturally with PEDV were randomly divided into three groups, receiving the basal diet containing 0, 750 and 1500 g/kg DON, respectively. We observed significant increases in the diarrhea rates, the villous injury of jejunums and the PEDV proliferation of duodenum, jejunum, ileum and mesenterium of piglets in experimental groups compared with control. Additionally, the autophagosome-like vesicles and the autophagy-related protein expressions were also increased in experimental groups. In vitro, we observed that, approximately 2 hrs post-infection, 0.1, 0.5 and 1.0 M DON promoted PEDV entry (P < 0.05) in IPEC-J2s and resulted in tight junction protein occludin internalization. Knockdown of occludin and CRISPR-Cas9-mediated knockout of LC3B indicated a vital role of autophagy-induced occludin internalization in DON-promoted PEDV entry. We also observed that, 24 hrs post-infection, a significant increase in PEDV replication after 0.1, 0.5 and 1.0 M DON treatment, along with the induction of a complete autophagy. Specifically, deletion of LC3B indicated a crucial role of autophagy in DON-promoted PEDV replication. Pretreatment with SB202190, a p38 signaling inhibitor, abolished the induction of autophagy. Furthermore, downregulation of type I interferon revealed that DON contributed PEDV to escape innate immune. Mechanistically, DON-caused innate immune escape was related to the upregulation of LC3B, which further inhibited STING phosphorylation. Taken together, DON could promote PEDV infection by inducing occludin internalization and innate immune escape via triggering p38-mediated autophagy. Author summaryPorcine epidemic diarrhea (PED), a devastating enteric disease, leads to catastrophic economic loss to the global pig industry. Its primary pathogen is the coronavirus PED virus (PEDV). Growing evidence indicates that pathogen infection is not the only factor of PED outbreaks, other non-infectious factors is also related to this disease. We guessed some ubiquitous substances, such as deoxynivalenol (DON), that lead to pig intestinal epithelial cell stress might encourage the progress and spread of PED. In the present study, the weaning piglets infected naturally with PEDV and the IPEC-J2 cell line were selected as models to explore the effects of DON on PEDV infection, morbidity and gut barrier. Our results showed that DON exposure can promote PEDV infection in vitro and in vivo, and the underlying mechanism might be related to LC3B-mediated autophagy. Our findings reveal new pathways for developing potential novel antiviral strategies against PEDV infection.

immunology↗

bioRxiv2019

Existence and functions of hypothalamic kisspeptin neuropeptide signaling system in a non-chordate deuterostome species

The kisspeptin (Kp) system is a central modulator of the hypothalamic-pituitary-gonadal axis in vertebrates. Its existence outside the vertebrate lineage remains largely unknown. Here we report the identification and characterization of Kp system in the sea cucumber Apostichopus japonicus. The gene encoding the Kp precursor, generates two mature neuropeptides, AjKiss1a and AjKiss1b. The Kp receptors, AjKissR1 and AjKissR2, are strongly activated by synthetic A. japonicus and vertebrate Kps, triggering a rapid intracellular mobilization of Ca2+, followed by receptor internalization. AjKissR1 and AjKissR2 share similar intracellular signaling pathways via Gq/PLC/PKC/MAPK cascade, when activated by C-terminal decapeptide (AjKiss1b-10). The A. japonicus Kp system functions in mutiple tissues which are closely related to reproduction and metabolism. Overall, our findings uncover for the first time, to our knowledge, the existence and function of the Kp system in a non-chordate species and provide new evidence to support the ancient origin of the hypothalamic neurosecretory system.

evolutionary biology↗

bioRxiv2019

A whole-genome scan for association with invasion success in the fruit fly Drosophila suzukii using contrasts of allele frequencies corrected for population structure

Evidence is accumulating that evolutionary changes are not only common during biological invasions but may also contribute directly to invasion success. The genomic basis of such changes is still largely unexplored. Yet, understanding the genomic response to invasion may help to predict the conditions under which invasiveness can be enhanced or suppressed. Here we characterized the genome response of the spotted wing drosophila Drosophila suzukii during the worldwide invasion of this pest insect species, by conducting a genome-wide association study to identify genes involved in adaptive processes during invasion. Genomic data from 22 population samples were analyzed to detect genetic variants associated with the status (invasive versus native) of the sampled populations based on a newly developed statistic, we called C2, that contrasts allele frequencies corrected for population structure. This new statistical framework has been implemented in an upgraded version of the program BO_SCPLOWAYC_SCPLOWPO_SCPLOWASSC_SCPLOW. We identified a relatively small set of single nucleotide polymorphisms (SNPs) that show a highly significant association with the invasive status of populations. In particular, two genes RhoGEF64C and cpo, the latter contributing to natural variation in several life-history traits (including diapause) in Drosophila melanogaster, contained SNPs significantly associated with the invasive status in the two separate main invasion routes of D. suzukii. Our methodological approaches can be applied to any other invasive species, and more generally to any evolutionary model for species characterized by non-equilibrium demographic conditions for which binary covariables of interest can be defined at the population level.

evolutionary biology↗

bioRxiv2019

Osmotic stress-induced, rapid clustering of IGF2BP proteins nucleates stress granule assembly

Stress granules (SGs) are formed in the cytoplasm by liquid-liquid phase separation (LLPS) of translationally-stalled mRNA and RNA-binding proteins during stress response. Understanding the mechanisms governing SG assembly requires imaging SG formation in real time. Here we used live cell imaging and super-resolution imaging to visualize SG assembly in human cells. We found that IGF2BP proteins formed microscopically visible clusters almost instantaneously upon osmotic stress, prior to the recruitment of G3BP1 and TIA1. The rapid clustering of IGF2BP1 was ATP-independent and was mediated by its KH3/4 di-domains and an intrinsically disordered region (IDR), whereas ATP depletion inhibited the recruitment of G3BP1 and TIA1. Moreover, we detected cytoplasmic clusters of IGF2BP1 below the optical resolution in normal cells and found IGF2BP1 forming a dense granule associated with multiple clusters of poly(A) mRNA in mature SGs. Thus, ATP-independent, rapid clustering of IGF2BP nucleates SG assembly during osmotic stress.

cell biology↗

bioRxiv2019

The transcriptomic response of cells to a drug combination is more than the sum of the responses to the monotherapies

Our ability to predict the effects of drug combinations is limited, in part by limited understanding of how the transcriptional response of two monotherapies results in that of their combination. We performed the first analysis of matched time course RNAseq profiling of cells treated with both single drugs and their combinations. The transcriptional signature of the synergistic combination we studied had unique gene expression not seen in either constituent monotherapy. This can be explained mechanistically by the sequential activation of transcription factors in time in the gene regulatory network. The nature of this transcriptional cascade suggests that drug synergy may ensue when the transcriptional responses elicited by two unrelated individual drugs are correlated. We used these results as the basis of a simple prediction algorithm attaining an AUROC of 0.84 in the prediction of synergistic drug combinations in an independent dataset.

cell biology↗

bioRxiv2019

An integrative resource for investigating genetic model of drug response in cancer

BackgroundThe most important goal of pharmacogenetics research is to obtain genetic models closely related to drug efficacy in vivo and in vitro, which can be used to measure individual responses and then to assess the sensitivity and toxicity of anticancer drugs. However, these models are scattered in different pharmacogenetic studies and are difficult to be effectively used and analyzed. ResultsTo this end, we have developed an integrated resource named iGMDR that provides the genetic models of both clinical and preclinical anticancer drugs. iGMDR provides a unique resource for mining the links between anticancer drugs and individual genomes, which will attempt to discover cancer knowledge and unlock the potential value of this data. ConclusionsWe developed iGMDR as a web service whose code was released at GitHub repository of ModelLAB (https://github.com/ModelLAB-ZJU/iGMDR), it also provided online access and application interface (https://igmdr.modellab.cn). MySQL dump for the integrated resources was stored at zenodo.org (DOI: 10.5281/ zencomod.1432561).

bioinformatics↗

bioRxiv2019

A deep learning framework for improving protein interaction prediction using sequence properties

MotivationAlmost all critical functions and processes in cells are sustained by the cellular networks of protein-protein interactions (PPIs), understanding these is therefore crucial in the investigation of biological systems. Despite all past efforts, we still lack high-quality PPI data for constructing the networks, which makes it challenging to study the functions of association of proteins. High-throughput experimental techniques have produced abundant data for systematically studying the cellular networks of a biological system and the development of computational method for PPI identification. ResultsWe have developed a deep learning-based framework, named iPPI, for accurately predicting PPI on a proteome-wide scale depended only on sequence information. iPPI integrates the amino acid properties and compositions of protein sequence into a unified prediction framework using a hybrid deep neural network. Extensive tests demonstrated that iPPI can greatly outperform the state-of-the-art prediction methods in identifying PPIs. In addition, the iPPI prediction score can be related to the strength of protein-protein binding affinity and further showed the biological relevance of our deep learning framework to identify PPIs. Availability and ImplementationiPPI is available as an open-source software and can be downloaded from https://github.com/model-lab/deeplearning.ppi Contactxiang-chen@zju.edu.cn

bioinformatics↗