Biology subjects

Yang, Y.

Publications and source records attributed to Yang, Y..

At least 1,189 records · Page 66Linked to original sources

bioRxiv2020

Dietary propionate induces intestinal oxidative stress via inhibition of SIRT3-mediated SOD2 depropionylation

Propionate is a commonly used preservative in various food and feedstuffs and has been regarded as a food additive without safety concerns. However, we observed that dietary propionate supplementation induced intestinal damage in the context of high fat diet (HFD) in zebrafish. The intestinal damage was attributable to oxidative stress owing to impaired antioxidant capacity, which was caused by compromised SOD2 activity in the intestine. Global lysine propionylation analysis of the intestinal samples showed that SOD2 was propionylated at K132, and further biochemical assays demonstrated that K132 propionylation suppressed SOD2 activity. In addition, SIRT3 could directly interact with SOD2 and played an important role in regulating SOD2 activity via modulating depropionylation, and the enhanced SOD2 propionylation in zebrafish fed high fat plus propionate diet was attributable to reduced SIRT3 expression. Finally, we reveal that intestinal oxidative stress resulting from SOD2 propionylation contributed to the compositional change of gut microbiota, which further deteriorated intestinal oxidative stress independent of SIRT3. Collectively, the results in this study reveal a link between protein propionylation and intestine health, and suggest potential risk of a widely used food preservative in HFD context.

cell biology↗

bioRxiv2020

Nonlinear System Identification of Neural Systems from Neurophysiological Signals

The human nervous system is one of the most complicated systems in nature. Complex nonlinear behaviours have been shown from the single neuron level to the system level. For decades, linear connectivity analysis methods, such as correlation, coherence and Granger causality, have been extensively used to assess the neural connectivities and input-output interconnections in neural systems. Recent studies indicate that these linear methods can only capture a small amount of neural activities and functional relationships, and therefore cannot describe neural behaviours in a precise or complete way. In this review, we highlight recent advances in nonlinear system identification of neural systems, corresponding time and frequency domain analysis, and novel neural connectivity measures based on nonlinear system identification techniques. We argue that nonlinear modelling and analysis are necessary to study neuronal processing and signal transfer in neural systems quantitatively. These approaches can hopefully provide new insights to advance our understanding of neurophysiological mechanisms underlying neural functions. These nonlinear approaches also have the potential to produce sensitive biomarkers to facilitate the development of precision diagnostic tools for evaluating neurological disorders and the effects of targeted intervention.

neuroscience↗

bioRxiv2020

Aerobic glycolysis supports hepatitis B virus biosynthesis through interaction between viral surface antigen and pyruvate kinase isoform M2

As an intracellular pathogen, the reproduction of hepatitis B virus (HBV) depends on the occupancy of host metabolism machinery. Here we test a hypothesis if HBV may govern intracellular biosynthesis to achieve a productive reproduction. To test this hypothesis, we set up an affinity purification screen for host factors that interact with viral large surface antigen (LHBS). This identified pyruvate kinase isoform M2 (PKM2), a key regulator of glucose metabolism, as a binding partner of LHBS. We showed that the expression of LHBS affected oligomerization of PKM2 in hepatocytes, and thereby increased glucose consumption and lactate production, a phenomenon known as aerobic glycolysis. Interestingly, recovering PKM2 activity in hepatocytes by chemical activators, TEPP-46 or DASA-58, reduced biosynthesis of viral surface and core antigens. In addition, reduction of glycolysis by culturing in low-glucose condition or treatment with 2-deoxyglucose also decreased biosynthesis of viral surface antigen, without affecting general host proteins. Finally, TEPP-46 largely suppressed proliferation of LHBS-positive cells on 3-dimensional agarose plates, but showed no effect on the traditional 2-dimensional cell culture. Taken together, these results indicate that virus-induced metabolic switch may support de novo biosynthesis of HBV in hepatocytes. In addition, aerobic glycolysis is likely essential for LHBS-mediated oncogenesis. Accordingly, restriction of glucose metabolism may be considered as a novel strategy to restrain viral mediated biosynthesis and oncogenesis during chronic HBV infection. Author summaryChronic HBV infection is a life-long threat of patients, with a 25~40% increased risk of developing liver cirrhosis and cancer. Persistent expression of oncogenic viral products in the liver, especially LHBS, is an oncogenic caveat and resistant to current antiviral agents. Here we show that viral LHBS binds to host PKM2 and diminishes its kinase activity. This virus-host interaction induces metabolic switch from oxidative phosphorylation to aerobic glycolysis, with increased glucose consumption and lactate production. We show that such metabolic switch not only favors biosynthesis of HBV but also provokes hepatocarcinogenesis. Notably, restoration of PKM2 activity by chemical activators decreases expressions of viral products and largely suppresses virus-mediated hepatocarcinogenesis. This study highlights the importance of host metabolism in supporting viral biosynthesis and indicates a novel therapeutic approach to control chronic HBV infection via modulating host metabolic switch.

microbiology↗

bioRxiv2020

A valid protective immune response elicited in rhesus macaques by an inactivated vaccine is capable of defending against SARS-CoV-2 infection

With the relatively serious global epidemic outbreak of SARS-CoV-2 infection, public concerns focus on not only clinical therapeutic measures and public quarantine for this disease but also the development of vaccines. The technical design of our SARS-CoV-2 inactivated vaccine provides a viral antigen that enables the exposure of more than one structural protein based upon the antibody composition of COVID-19 patients convalescent serum. This design led to valid immunity with increasing neutralizing antibody titers and a CTL response detected post-immunization of this vaccine by two injections in rhesus macaques. Further, this elicited immunoprotection in macaques enables not only to restrain completely viral replication in tissues of immunized animals, compared to the adjuvant control and those immunized by an RBD peptide vaccine, but also to significantly alleviate inflammatory lesion in lung tissues in histo-pathologic detection, compared to the adjuvant control with developed interstitial pneumonia. The data obtained from these macaques immunized with the inactivated vaccine or RBD peptide vaccine suggest that immunity with a clinically protective effect against SARS-CoV-2 infection should include not only specific neutralizing antibodies but also specific CTL responses against at least the S and N antigens.

immunology↗

bioRxiv2020

Interannual variability of net ecosystem carbon production and its climatic and biotic mechanism during 2005-2018 in a rain-fed maize ecosystem

The interannual variation (IAV) of net ecosystem carbon production (NEP) plays an important role in understanding the mechanisms of the carbon cycle in the agriculture ecosystem. In this study, the IAV of NEP, which were expressed as annual values and anomalies, and its climatic and biotic controls mechanism, were investigated based on an eddy covariance dataset of rain-fed spring maize during 2005-2018 in the northeast of China. The annual NEP was 270{+/-}115 g C m-2yr -1. Annual values and anomalies of NEP were positively correlated with that of precipitation (PPT), gross ecosystem production (GEP) and daily maximum NEP (NEPmax). Annual anomalies of NEP were dominantly and positively controlled by the soil water content (SWC) through GEP and the soil temperature (Ts) through RE. In comparison, annual anomalies of NEP were dominantly and negatively controlled by summer VPD through the NEPmax, positively adjusted by spring precipitation and the effective accumulative temperature through the beginning date (BDOY) of the affecting carbon uptake period (CUP), and by autumn precipitation and leaf area index through the end date (EDOY) of the affecting CUP. Residues restrained the carbon release at the beginning of the year, and accelerated the carbon release at the end of the year. Our results hightlight that NEP might be more sensitive to the change of water condition (such as PPT, SWC and VPD) induced by the climate changes.

ecology↗

bioRxiv2020

A dynamic regulatory interface on SARS-CoV-2 RNA polymerase

The RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2 is the core machinery responsible for the viral genome replication and transcription and also a major antiviral target. Here we report the cryo-electron microscopy structure of a post-translocated SARS-CoV-2 RdRp core complex, comprising one nsp12, one separate nsp8(I) monomer, one nsp7-nsp8(II) subcomplex and a replicating RNA substrate. Compared with the recently reported SARS-CoV-2 RdRp complexes, the nsp8(I)/nsp7 interface in this RdRp complex shifts away from the nsp12 polymerase. Further functional characterizations suggest that specific interactions between the nsp8(I) and nsp7, together with the rearrangement of nsp8(I)/nsp7 interface, ensure the efficient and processive RNA synthesis by the RdRp complex. Our findings provide a mechanistic insight into how nsp7 and nsp8 cofactors regulate the polymerase activity of nsp12 and suggest a potential new intervention interface, in addition to the canonical polymerase active center, in RdRp for antiviral design. Author summarySince it was first discovered and reported in late 2019, the coronavirus disease 2019 (COVID-19) pandemic caused by highly contagious SARS-CoV-2 virus is wreaking havoc around the world. Currently, no highly effective and specific antiviral drug is available for clinical treatment. Therefore, the threat of COVID-19 transmission necessitates the discovery of more effective antiviral strategies. Viral RNA-dependent RNA polymerase (RdRp) is an important antiviral drug target. Here, our cryo-EM structure of a SARS-CoV-2 RdRp/RNA replicating complex reveals a previously uncharacterized overall shift of the cofactor nsp8(I)/nsp7 interface, leading to its rearrangement. Through in vitro functional test, we found that the specific interactions on the interface are important to the efficient RNA polymerase activity of SARS-CoV-2 RdRp. These observations let us to suggest this interface as a potential new drug intervention site, outside of the canonical polymerase active center, in RdRp for antiviral design. Our findings would provide new insights into regulatory mechanism of this novel SARS-CoV-2 RdRp, contribute to the design of antiviral drugs against SARS-CoV-2, and benefit the global public health.

molecular biology↗

bioRxiv2020

Common variants contribute to intrinsic functional architecture of human brain

The human brain remains active in the absence of explicit tasks and forms networks of correlated activity. Resting-state functional magnetic resonance imaging (rsfMRI) measures brain activity at rest, which has been linked with both cognitive and clinical outcomes. The genetic variants influencing human brain function are largely unknown. Here we utilized rsfMRI from 44,190 individuals of multiple ancestries (37,339 in the UK Biobank) to discover and validate the common genetic variants influencing intrinsic brain activity. We identified hundreds of novel genetic loci associated with intrinsic functional signatures (P < 2.8 x 10-11), including associations to the central executive, default mode, and salience networks involved in the triple network model of psychopathology. A number of intrinsic brain activity associated loci colocalized with brain disorder GWAS (e.g., Alzheimers disease, Parkinsons disease, schizophrenia) and cognition, such as 19q13.32, 17q21.31, and 2p16.1. Particularly, we detected a colocalization between one (rs429358) of the two variants in the APOE {varepsilon}4 locus and function of the default mode, central executive, attention, and visual networks. Genetic correlation analysis demonstrated shared genetic influences between brain function and brain structure in the same regions. We also detected significant genetic correlations with 26 other complex traits, such as ADHD, major depressive disorder, schizophrenia, intelligence, education, sleep, subjective well-being, and neuroticism. Common variants associated with intrinsic brain activity were enriched within regulatory element in brain tissues.

genetics↗

bioRxiv2020

Genome wide identification of QTL associated with yield and yield components in two popular wheat cultivars TAM 111 and TAM 112

Two drought-tolerant wheat cultivars, TAM 111 and TAM 112, have been widely grown in the Southern Great Plains of the U.S. and used as parents in many wheat breeding programs worldwide. This study aimed to reveal genetic control of yield and yield components in the two cultivars under both dryland and irrigated conditions. A mapping population containing 124 F5:7 recombinant inbred lines (RILs) was developed from the cross of TAM 112/TAM 111. A set of 5,948 SNPs from the wheat 90K iSelect array and double digest restriction-site associated DNA sequencing was used to construct high-density genetic maps. Data for yield and yield components were obtained from 11 environments. QTL analyses were performed based on 11 individual environments, across all environments, within and across mega-environments. Thirty-six unique consistent QTL regions were distributed on 13 chromosomes including 1A, 1B, 1D, 2A, 2D, 3D, 4B, 4D, 6A, 6B, 6D, 7B, and 7D. Ten unique QTL with pleiotropic effects were identified on four chromosomes and eight were in common with the consistent QTL. These QTL increased dry biomass grain yield by 16.3 g m-2, plot yield by 28.1 g m-2, kernels spike-1 by 0.7, spikes m-2 by 14.8, thousand kernel weight by 0.9 g with favorable alleles from either parent. TAM 112 alleles mainly increased spikes m-2 and thousand kernel weight while TMA 111 alleles increased kernels spike-1, harvest index and grain yield. The saturated genetic map and markers linked to significant QTL from this study will be very useful in developing high throughput genotyping markers for tracking the desirable haplotypes of these important yield-related traits in popular parental cultivars.

genetics↗

bioRxiv2020

Regeneration of Functional Retinal Ganglion Cells by Neuronal Identity Reprogramming

Degeneration of retinal ganglion cells (RGCs) and their axons underlies vision loss in glaucoma and various optic neuropathies. There are currently no treatments available to restore lost vision in patients affected by these diseases. Regenerating RGCs and reconnecting the retina to the brain represent an ideal therapeutic strategy; however, mammals do not have a reservoir of retinal stem/progenitor cells poised to produce new neurons in adulthood. Here, we regenerated RGCs in adult mice by direct lineage reprogramming of retinal interneurons. We successfully converted amacrine and displaced amacrine interneurons into RGCs, and observed that regenerated RGCs projected axons into brain retinorecipient areas. They convey visual information to the brain in response to visual stimulation, and are able to transmit electrical signals to postsynaptic neurons, in both normal animals and in a diseased model. The generation of functional RGCs in adult mammals points to a therapeutic strategy for vision restoration in patients.

neuroscience↗

bioRxiv2020

A high-quality de novo genome assembly from a single parasitoid wasp

Sequencing and assembling a genome with a single individual have several advantages, such as lower heterozygosity and easier sample preparation. However, the amount of genomic DNA of some small sized organisms might not meet the standard DNA input requirement for current sequencing pipelines. Although few studies sequenced a single small insect with about 100 ng DNA as input, it may still be challenging for many small organisms to obtain such amount of DNA from a single individual. Here, we use 20 ng DNA as input, and present a high-quality genome assembly for a single haploid male parasitoid wasp (Habrobracon hebetor) using Nanopore and Illumina. Because of the low input DNA, a whole genome amplification (WGA) method is used before sequencing. The assembled genome size is 131.6 Mb with a contig N50 of 1.63 Mb. A total of 99% Benchmarking Universal Single-Copy Orthologs are detected, suggesting the high level of completeness of the genome assembly. Genome comparison between H. hebetor and its relative Bracon brevicornis shows a high-level genome synteny, indicating the genome of H. hebetor is highly accurate and contiguous. Our study provides an example for de novo assembling a genome from ultra-low input DNA, and will be used for sequencing projects of small sized species and rare samples, haploid genomics as well as population genetics of small sized species.

genomics↗

bioRxiv2020

RNF219 interacts with CCR4-NOT in regulating stem cell differentiation

Regulation of RNA stability plays a crucial role in gene expression control. Deadenylation is the initial rate-limiting step for the majority of RNA decay events. Here, we show that RING Finger Protein 219 (RNF219) interacts with the CCR4-NOT deadenylase complex. RNF219-CCR4-NOT exhibits deadenylation activity in vitro. RNA-seq analyses identify some of the 2-cell specific genes and the neuronal genes significantly down-regulated upon RNF219 knockdown, while up-regulated after depletion of the CCR4-NOT subunit CNOT10 in mouse embryonic stem (ES) cells. RNF219 depletion leads to impaired neuronal lineage commitment during ES cell differentiation. Our study suggests that RNF219 is a novel interacting partner of CCR4-NOT, and required for maintenance of ES cell pluripotency.View Full Text

molecular biology↗

bioRxiv2020

Calumenin contributes to epithelial-mesenchymal transition and predicts poor survival in glioma

Calumenin (CALU) has been reported to be associated with invasiveness and metastasis in some malignancies. However, in glioma, the role of CALU remains unclear. In the current study, we aimed to unveil its role in glioma based on transcriptome level. Clinical and transcriptome data of 998 glioma patients, including 301 from CGGA mRNA microarray dataset and 697 from TCGA RNA sequencing dataset, were downloaded and analyzed. R language was used to perform statistical analyses and generate figures. In glioma, CALU expression seemed to be positively associated with WHO grade system, and was enriched in IDH wildtype, mesenchymal and classical subtype. Genes that tightly correlated with CALU were screened and annotated with Gene Ontology, and it turned out that, these genes were highly enriched in cell/biological adhesion, response to wounding, and extracellular matrix/structure organization, all of which were strongly correlated with the epithelial-mesenchymal transition (EMT) phenotype. Subsequent GSEA analysis further validated the profound involvement of CALU in EMT. To get further understanding of the association between EMT and CALU, GSVA analysis was performed to identify the EMT signaling pathways that CALU might involve. CALU expression was found to be positively correlated with TGFβ, PI3K/AKT, and hypoxia pathway. Furthermore, Pearson correlation indicated that CALU played synergistically with EMT key markers, including N-cadherin, vimentin, snail, slug and TWIST1, in both CGGA and TCGA dataset. Kaplan-Meier curves and Cox regression analyses showed that higher CALU predicted a worse survival for patients, and the prognostic value was independent of WHO grade and age. In conclusion, CALU was correlated with more malignant phenotypes in glioma. Moreover, CALU seemed to serve as a pro-EMT molecular target and could contribute to predict prognosis independently for glioma patients.Competing Interest StatementThe authors have declared no competing interest.View Full Text

cancer biology↗

bioRxiv2020

Revisiting the carbon isotope discrimination and water use efficiency relation: the influence of mesophyll conductance

SummaryThe carbon isotope discrimination (Δ) has been used widely to infer intrinsic water-use efficiency (iWUE) of C3 plants, a key parameter linking carbon and water fluxes. Despite the essential role of mesophyll conductance (gm) in photosynthesis and Δ, its effect on Δ-based predictions of iWUE has generally been neglected.Here, we derive a mathematical expression of iWUE as a function of Δ that includes gm (iWUEmes) and exploits the gm-stomatal conductance (gsc) relationship across drought-stress levels and plant functional groups (deciduous or semi-deciduous woody, evergreen woody and herbaceous species) in a global database. iWUEmes was further validated with an independent dataset of online-Δ and CO2 and H2O gas exchange measurements with seven species.Drought stress reduced gsc by 52% and gm by 45% averaged over all plant functional groups, but had no significant effect on the gsc/gm ratio, suggesting a well-constrained gsc/gm ratio of 0.79±0.07 (95%CI, n=198) across plant functional groups and drought-stress treatments. Due in part to the synchronous behavior of gsc and gm, gm was negatively correlated to iWUE. Incorporating the gsc/gm ratio in the iWUEmes model significantly improved the estimation of iWUE compared to the simple model.The inclusion of gm effects, even using a fixed gsc/gm ratio of 0.79 when gm is unknown, proved desirable to eliminate significant bias in estimating iWUE from Δ across various C3 vegetation types.Competing Interest StatementThe authors have declared no competing interest.View Full Text

plant biology↗

bioRxiv2020

Zinc finger protein SALL4 functions through an AT-rich motif to regulate heterochromatin formation

SummaryThe zinc finger transcription factor SALL4 is highly expressed in embryonic stem cells, down-regulated in most adult tissues, but reactivated in many aggressive cancers. This unique expression pattern makes SALL4 an attractive target for designing therapeutic strategies. However, whether SALL4 binds DNA directly to regulate gene expression is unclear and many of its targets in cancer cells remain elusive. Here, through an unbiased screen of protein binding microarray (PBM) and Cleavage Under Targets and Release Using Nuclease (CUT&RUN) experiments, we identified and validated the DNA binding domain of SALL4 and its consensus binding sequence. Combined with RNA-seq analyses after SALL4 knockdown, we discovered hundreds of new SALL4 target genes that it directly regulates in aggressive liver cancer cells, including genes encoding a family of Histone 3 Lysine 9-specific Demethylases (KDMs). Taken together, these results elucidated the mechanism of SALL4 DNA binding and revealed novel pathways and molecules to target in SALL4-dependent tumors.Competing Interest StatementThe authors have declared no competing interest.View Full Text

molecular biology↗

bioRxiv2020

Conformational dynamics of SARS-CoV-2 trimeric spike glycoprotein in complex with receptor ACE2 revealed by cryo-EM

The recent outbreaks of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its rapid international spread pose a global health emergency. The trimeric spike (S) glycoprotein interacts with its receptor human ACE2 to mediate viral entry into host-cells. Here we present cryo-EM structures of an uncharacterized tightly closed SARS-CoV-2 S-trimer and the ACE2-bound-S-trimer at 2.7-Å and 3.8-Å-resolution, respectively. The tightly closed S-trimer with inactivated fusion peptide may represent the ground prefusion state. ACE2 binding to the up receptor-binding domain (RBD) within S-trimer triggers continuous swing-motions of ACE2-RBD, resulting in conformational dynamics of S1 subunits. Noteworthy, SARS-CoV-2 S-trimer appears much more sensitive to ACE2-receptor than SARS-CoV S-trimer in terms of receptor-triggered transformation from the closed prefusion state to the fusion-prone open state, potentially contributing to the superior infectivity of SARS-CoV-2. We defined the RBD T470-T478 loop and residue Y505 as viral determinants for specific recognition of SARS-CoV-2 RBD by ACE2, and provided structural basis of the spike D614G-mutation induced enhanced infectivity. Our findings offer a thorough picture on the mechanism of ACE2-induced conformational transitions of S-trimer from ground prefusion state towards postfusion state, thereby providing important information for development of vaccines and therapeutics aimed to block receptor binding.Competing Interest StatementThe authors have declared no competing interest.View Full Text

molecular biology↗

bioRxiv2020

IKBIP is a novel EMT-related biomarker and predicts poor survival in glioma

Purpose I kappa B-interacting protein (IKBIP) in cancer has rarely been reported. This study aimed at investigating its expression pattern and biological function in brain glioma at transcriptional level.Methods We selected 301 glioma patients with microarray data from CGGA database and 697 glioma patients with RNAseq data from TCGA database. Transcriptome data and clinical data of 998 samples were analyzed. Statistical analysis and figure generating were performed with R language.Results We found that IKBIP expression showed positive correlation with WHO grade of glioma. IKBIP was increased in IDH wildtype and mesenchymal molecular subtype of glioma. Gene ontology analysis demonstrated that IKBIP was profoundly associated with extracellular matrix organization, cell-substrate adhesion and response to wounding in both pan-glioma and glioblastoma. Subsequent GSEA analysis revealed that IKBIP was particularly correlated with epithelial-to-mesenchymal transition (EMT). To further elucidate the relationship between IKBIP and EMT, we performed GSVA analysis to screen the EMT-related signaling pathways, and found that IKBIP expression was significantly associated with PI3K/AKT, hypoxia and TGF-β pathway. Moreover, IKBIP expression was found to be synergistic with key biomarkers of EMT, especially with N-cadherin, vimentin, snail, slug and TWIST1. Finally, higher IKBIP indicated significantly shorter survival for glioma patients.Conclusions IKBIP was associated with more aggressive phenotypes of gliomas.Furthermore, IKBIP was significantly involved in EMT and could serve as an independent prognosticator in glioma.Competing Interest StatementThe authors have declared no competing interest.View Full Text

cancer biology↗

bioRxiv2020

Heterogeneous adaptation of cysteine reactivity to a covalent oncometabolite

ABSTRACTMetabolism and signaling intersect in the genetic cancer syndrome hereditary leiomyomatosis and renal cell carcinoma (HLRCC), a disease in which mutation of the TCA cycle enzyme fumarate hydratase (FH) causes hyperaccumulation of fumarate. This electrophilic oncometabolite can alter gene activity at the level of transcription, via reversible inhibition of epigenetic dioxygenases, as well as posttranslationally, via covalent modification of cysteine residues. To better understand how metabolites function as covalent signals, here we report a chemoproteomic analysis of a kidney-derived HLRCC cell line. Building on previous studies, we applied a general reactivity probe to compile a dataset of cysteine residues sensitive to rescue of cellular FH activity. This revealed a broad upregulation of cysteine reactivity upon FH rescue, caused by an approximately equal proportion of transcriptional and posttranslational regulation in the rescue cell line. Gene ontology analysis highlights new targets and pathways potentially modulated by FH mutation. Comparison of the new dataset to literature studies highlights considerable heterogeneity in the adaptive response of cysteine-containing proteins in different models of HLRCC. Our analysis provides a resource for understanding the proteomic adaptation to fumarate accumulation, and a foundation for future efforts to exploit this knowledge for cancer therapy.Competing Interest StatementThe authors have declared no competing interest.View Full Text

cancer biology↗

bioRxiv2020

Structure-aware Protein Solubility Prediction From Sequence Through Graph Convolutional Network And Predicted Contact Map

MotivationProtein solubility is significant in producing new soluble proteins that can reduce the cost of biocatalysts or therapeutic agents. Therefore, a computational model is highly desired to accurately predict protein solubility from the amino acid sequence. Many methods have been developed, but they are mostly based on the one-dimensional embedding of amino acids that is limited to catch spatially structural information. ResultsIn this study, we have developed a new structure-aware method to predict protein solubility by attentive graph convolutional network (GCN), where the protein topology attribute graph was constructed through predicted contact maps from the sequence. GraphSol was shown to substantially out-perform other sequence-based methods. The model was proven to be stable by consistent R2 of 0.48 in both the cross-validation and independent test of the eSOL dataset. To our best knowledge, this is the first study to utilize the GCN for sequence-based predictions. More importantly, this architecture could be extended to other protein prediction tasks. AvailabilityThe package is available at http://biomed.nscc-gz.cn Contactyangyd25@mail.sysu.edu.cn Supplementary informationSupplementary data are available at Bioinformatics online.

bioinformatics↗