Biology subjects

Huang, W.

Publications and source records attributed to Huang, W..

At least 19 recordsLinked to original sources

bioRxiv2018

Root volatiles in plant-plant interactions I: Characterization of root sesquiterpene emissions from Centaurea stoebe and their effects on other plants

Volatile organic compounds (VOCs) emitted by plant leaves can influence the physiology of neighboring plants. In contrast to interactions above ground, little is known about the role of VOCs in belowground plant-plant interactions. Here, we characterize constitutive root volatile emissions of the spotted knapweed (Centaurea stoebe) and explore the impact of these volatiles on the germination and growth of different sympatric plant species. We show that C. stoebe roots emit high amounts of sesquiterpenes, with estimated release rates of (E)-{beta}-caryophyllene above 3 g g-1 dw h-1. Sesquiterpene emissions show little variation between different C. stoebe populations, but vary substantially between different Centaurea species. Through root transcriptome sequencing, we identify six root-expressed sesquiterpene synthases (TPSs). Two root-specific TPSs, CsTPS4 and CsTPS5, are sufficient to produce the full blend of emitted root sesquiterpenes. Volatile exposure experiments demonstrate that C. stoebe root volatiles have neutral to positive effects on the germination and growth of different sympatric neighbors. Thus, constitutive root sesquiterpenes produced by two C. stoebe TPSs are associated with facilitation of sympatric neighboring plants. The release of root VOCs may thus influence C. stoebe abundance and plant community structure in nature.

plant biology↗

bioRxiv2018

Root volatiles in plant-plant interactions II: Root terpenes from Centaurea stoebe modify Taraxacum officinale root chemistry and root herbivore growth

Volatile organic compounds (VOCs) emitted by plant roots can influence the germination and growth of neighboring plants. However, little is known about the effects of root VOCs on plant-herbivore interactions. The spotted knapeed (Centaurea stoebe) constitutively releases high amounts of sesquiterpenes into the rhizosphere. Here, we examine the impact of C. stoebe root VOCs on primary and secondary metabolites of sympatric Taraxacum officinale plants and the resulting plant-mediated effects on a generalist root herbivore, the white grub Melolontha melolontha. We show that exposure of T. officinale to C. stoebe root VOCs does not affect the accumulation of defensive secondary metabolites, but modulates carbohydrate and total protein levels in T. officinale roots. Furthermore, VOC exposure increases M. melolontha growth on T. officinale plants. Exposure of T. officinale to a major C. stoebe root VOC, the sesquiterpene (E)-{beta}-caryophyllene, partially mimics the effect of the full root VOC blend on M. melolontha growth. Thus, releasing root VOCs can modify plant-herbivore interactions of neighboring plants. The release of VOCs to increase the susceptibility of other plants may be a form of plant offense.

plant biology↗

bioRxiv2018

The Novel Mnk1/2 Degrader VNLG-152 Potently Inhibits TNBC Tumor Growth and Metastasis

Currently, there are no effective therapies for patients with triple-negative breast cancer (TNBC), an aggressive and highly metastatic disease. Activation of eukaryotic initiation factor 4E (eIF4E) by mitogen-activated protein kinase (MAPK)-interacting kinases 1 and 2 (Mnk1/2) play a critical role in the development, progression and metastasis of TNBC. Herein, we undertook a comprehensive study to evaluate the activity of a first-in-class Mnk1/2 protein degraders, in clinically relevant models of TNBC. These studies enabled us to identify racemic VNLG-152R as the most efficacious Mnk1/2 degrader. By targeting Mnk1/2 protein degradation (activity), VNLG-152R potently inhibited both Mnk-eIF4E and mTORC1 signaling pathways and strongly regulated downstream factors involved in cell cycle regulation, apoptosis, pro-inflammatory cytokines/chemokines secretion, epithelial-mesenchymal transition (EMT) and metastasis. Most importantly, orally bioavailable VNLG-152R exhibited remarkable antitumor and antimetastatic activities against cell line and patient-derived TNBC xenograft models, with no apparent host toxicity. Collectively, these studies demonstrate that targeting Mnk-eIF4E/mTORC1 signaling with a potent Mnk1/2 degrader, VNLG-152R, is a novel therapeutic strategy that can be developed as monotherapy for effective treatment of patients with primary/metastatic TNBC.

cancer biology↗

bioRxiv2018

Nuclear export of chimeric mRNAs depends on an lncRNA-triggered autoregulatory loop

Aberrant chromosomal translocations leading to tumorigenesis have been ascribed to the heterogeneously oncogenic functions. However, how fusion transcripts exporting remains to be declared. Here, we showed that the nuclear speckle-specific long non coding RNA MALAT1 controls chimeric mRNA export processes and regulates myeloid progenitor cell differentiation in malignant hematopoiesis. We demonstrated that MALAT1 regulates chimeric mRNAs export in an m6A-dependent manner and thus controls hematopoietic cell differentiation. Specifically, reducing MALAT1 or m6A methyltransferases and the reader YTHDC1 result in the universal retention of distinct oncogenic gene mRNAs in nucleus. Mechanically, MALAT1 hijacks both the chimeric mRNAs and fusion proteins in nuclear speckles during chromosomal translocations and mediates the colocalization of oncogenic fusion proteins with METTL14. MALAT1 and fusion protein complexes serve as a functional loading bridge for the interaction of chimeric mRNA and METTL14. This study demonstrated a universal mechanism of chimeric mRNA transport that involves lncRNA-fusion protein-m6A autoregulatory loop for controlling myeloid cell differentiation. Targeting the lncRNA-triggered autoregulatory loop to disrupt chimeric mRNA transport might represent a new common paradigm for treating blood malignancies.

cancer biology↗

bioRxiv2018

Quantifying Heterogeneity in the Genetic Architecture of Complex Traits Between Ethnically Diverse Groups using Random Effect Interaction Models

In humans, most genome-wide association studies have been conducted using data from Caucasians and many of the reported findings have not replicated in other populations. This lack of replication may be due to statistical issues (small sample size, confounding) or perhaps more fundamentally to differences in the genetic architecture of traits between ethnically diverse subpopulations. What aspects of the genetic architecture of traits vary between subpopulations and how can this be quantified? We consider studying effect heterogeneity using random-effect Bayesian interaction models. The proposed methodology can be applied using shrinkage and variable selection methods and produces useful information about effect heterogeneity in the form of whole-genome summaries (e.g., SNP-heritability and the average correlation of effects) as well as SNP-specific attributes. Using simulations, we show that the proposed methodology yields (nearly) unbiased estimates of genomic heritability and of the average correlation of effects between groups when the sample size is not too small relative to the number of SNPs used. Subsequently, we used the proposed methodology for the analyses of four complex human traits (standing height, high-density lipoprotein, low-density lipoprotein, and serum urate levels) in European-Americans (EAs) and African-Americans (AAs). The estimated correlations of effects between the two subpopulations was well below unity for all the traits, ranging from 0.73 to 0.50. The extent of effect heterogeneity varied between traits and SNP-sets. Height showed less differences in SNP effects between AAs and EAs whereas HDL, a trait highly influenced by life-style, exhibited greater extent of effect heterogeneity. For all the traits we observed substantial variability in effect heterogeneity across SNPs, suggesting it varies between regions of the genome.

genetics↗

bioRxiv2018

HBx enhances CPAP expression via interacting with CREB to promote hepatocarcinogenesis in HBV-associated HCC

Hepatitis B virus (HBV) encoded non-structure protein X (HBx) can promote cell proliferation, migration, and anti-apoptosis via activating several transcription factors and increasing their downstream gene expression in HBV-infected liver cells. Our previous report suggested that centrosomal P4.1-associated protein (CPAP) is required for HBx-mediated NF-{kappa}B activation. Here, we found that, upon HBV infection, overexpressed HBx can transcriptionally up-regulate CPAP via interacting with CREB. CPAP can directly interact with HBx to promote HBx-mediated cell proliferation and migration; and SUMO modification of CPAP is involved in interacting with HBx. Interestingly, CPAP can increase the HBx protein stability in an NF-{kappa}B-dependent manner; and overexpressed CPAP and HBx is positively correlated with the activation status of NF-{kappa}B in HCC. Increased expression of CREB and CPAP mRNAs exists in the high-risk group with a lower survival rate in hepatocellular carcinoma (HCC). These results suggest that the reciprocal regulation between CPAP and HBx may provide a microenvironment to facilitate HCC development via enhancing NF-{kappa}B activation, inflammatory cytokine production, and cancer maligancies. The findings of this study not only shed light on the role of CPAP in HBV-associated HCC, but also provide CPAP as a potential target for HBV-related HCC therapy.\n\nAuthor SummaryIn this study, we address a novel molecular mechanism for the collaboration between overexpressed HBx and CPAP in promoting hepatocarcinogenesis in HBV-associated HCC. Upon HBV infection, HBx is overexpressed and interacts with CREB to transcriptionally activate CPAP; the HBx/CPAP interaction promotes hepatocarcinogenesis. Clinical analysis found that co-overexpressed CPAP and CREB exist in the high-risk group with a lower survival rate in HCC. Additionally, overexpressed CPAP contributes to HBx protein stability in a NF-{kappa}B-dependent pathway. Our study provides a potential translational application in targeting CREB-CPAP axis in HBV-associated HCC.

cancer biology↗

bioRxiv2018

A novel core genome approach to enable prospective and dynamic monitoring of infectious outbreaks

Whole-genome sequencing is increasingly adopted in clinical settings to identify pathogen transmissions. Currently, such studies are performed largely retrospectively, but to be actionable they need to be carried out prospectively, in which samples are continuously added and compared to previous samples. To enable prospective pathogen comparison, genomic relatedness metrics based on single nucleotide differences must be consistent across time, efficient to compute and reliable for a large variety of samples. The choice of genomic regions to compare, i.e., the core genome, is critical to obtain a good metric.\n\nWe propose a novel core genome method that selects conserved sequences in the reference genome by comparing its k-mer content to that of publicly available genome assemblies. The conserved-sequence genome is sample set-independent, which enables prospective pathogen monitoring. Based on clinical data sets of 3436 S. aureus, 1362 K. pneumoniae and 348 E. faecium samples, we show that the conserved-sequence genome disambiguates same-patient samples better than a core genome consisting of conserved genes. The conserved-sequence genome confirms outbreak samples with high accuracy: in a set of 2335 S. aureus samples, it correctly identifies 44 out of 45 outbreak samples, whereas the conserved gene method confirms 38 out of 45 outbreak samples.

bioinformatics↗

bioRxiv2018

Characterisation and development of aspirin inducible biosensors in E. coli Nissle 1917 and SimCells

A simple aspirin-inducible system has been developed by employing the Psal promoter and SalR regulation system originally from Acinetobacter baylyi ADP1, which has been cloned into E. coli for characterisation of gene circuits and induction of novel SimCells (simple cells). Mutagenesis at the DNA binding domain (DBD) and chemical recognition domain (CRD) of the SalR protein in A. baylyi ADP1 suggests that inactive SalRi can compete with activated SalRa, occupying the binding position of Psal promoter. The induction of the Psal promoter was compared in two different designs in E. coli: simple regulation (SRS) and positive autoregulated system (PAR). Both regulatory systems were induced in a dose-dependent manner in the presence of aspirin in the range of 0.05-10 M. Over-expression of SalR in the SRS system reduces both baseline leakiness and inducible strength of Psal promoter. A weak SalR expression significantly improve the inducible strength, which is in a good agreement of the proposed hypothesis of SalRi/SalRa competitive binding. The PAR system provides a feedback loop that fine-tunes the level of SalR, displaying inducible strength. A mathematical model based on SalRi/SalRa competitive binding hypothesis was developed, which not only reproduces the observed experimental results but also predict the performance of a new gene circuit design. The aspirin-inducible systems were also functional in probiotic strain E.coli Nissle 1917 (EcN) and SimCells produced from E. coli MC1000 {Delta}minD. The well-characterised and modularised aspirin-inducible gene circuits would be useful biobricks for bacterial therapy in environment and medical applications.

microbiology↗

bioRxiv2018

Integrative analysis of Zika virus genome RNA structure reveals critical determinants of viral infectivity

Since its outbreak in 2007, Zika virus (ZIKV) has become a global health threat that causes severe neurological conditions. Here we perform a comparative in vivo structural analysis of the RNA genomes of two ZIKV strains to decipher the regulation of their infection at the RNA level. Our analysis identified both known and novel functional RNA structural elements. We discovered a functional long-range intramolecular interaction specific for the Asian epidemic strains, which contributes to their infectivity. Our findings illuminate the structural basis of ZIKV regulation and provide a rich resource for the discovery of RNA structural elements that are important for ZIKV infection.

molecular biology↗

bioRxiv2018

Population based hospitalization burden of laboratory-confirmed hand, foot and mouth disease caused by multiple enterovirus serotypes in southern China

BackgroundHand, foot and mouth disease (HFMD) is spread widely across Asia, and the hospitalization burden is as yet not well understood. Here, we estimated serotype-specific and age-specific hospitalization rates of HFMD in Southern China.\n\nMethodsWe enrolled pediatric patients admitted to 3/3 county-level hospitals and 3/23 township level hospitals in Anhua county, Hunan (CN) with HFMD, and collected samples to identify enterovirus serotypes by RT-PCRs between October 2013 and September 2016. The information of other eligible but un-enrolled patients were retrospectively collected from the same six hospitals. Monthly number of hospitalizations for all causes was collected from each of 23 township level hospitals to extrapolate hospitalizations associated with HFMD among these.\n\nResultsDuring the three years, an estimated 3,236 pediatric patients were hospitalized with lab-confirmed HFMD, and among these only one patient was severe. The mean hospitalization rates were 660 (95% CI: 638-684) per 100,000 person-years for lab-confirmed HFMD, with higher rates among CV-A16 and CV-A6 associated HFMD (213 vs 209 per 100,000 person-years), and lower among EV-A71, CV-A10 and other enteroviruses associated HFMD (134, 39 and 66 per 100,000 person-years, p<0.001). Children aged 12-23 months had the highest hospitalization rates (3,594/100,000 person-years), followed by those aged 24-35 months (1,828/100,000 person-years) and 6-11 months (1,572/100,000 person-years). Compared with other serotypes, CV-A6-associated hospitalizations were evident at younger ages.\n\nConclusionsOur study indicates a substantial hospitalization burden associated with non-severe HFMD in a rural county in southern China. Future mitigation policies should take into account the disease burden identified, and optimize interventions for HFMD.

epidemiology↗

bioRxiv2018

Dynamic Regulation of RNA Structure in Mammalian Cells

RNA structure is intimately connected to each step of gene expression. Recent advances have enabled transcriptome-wide maps of RNA secondary structure, termed RNA structuromes. However, previous whole-cell analyses lacked the resolution to unravel the dynamic regulation of RNA structure across subcellular states. Here we reveal the RNA structuromes in three compartments -- chromatin, nucleoplasm and cytoplasm. The cytotopic structuromes substantially expand RNA structural information, and enable detailed investigation of the central role of RNA structure in linking transcription, translation, and RNA decay. Through comparative structure analysis, we develop a resource to visualize the interplay of RNA-protein interactions, RNA chemical modifications, and RNA structure, and predict both direct and indirect reader proteins of RNA modifications. We validate the novel role of the RNA binding protein LIN28A as an N6-methyladenosine (m6A) modification \"anti-reader\". Our results highlight the dynamic nature of RNA structures and its functional significance in gene regulation.

molecular biology↗

bioRxiv2018

Stochastic population dynamics driven by mutant interactors

Spontaneous random mutations are an important source of variation in populations. Many evolutionary models consider mutants with a fixed fitness chosen from a certain fitness distribution without considering any interactions among the residents and mutants. Here, we go beyond this and consider \"mutant interactors\", which lead to new interactions between the residents and invading mutants that can affect the carrying capacity and the extinction risk of populations. We model microscopic interactions between individuals by using a dynamical payoff matrix and analyze the stochastic dynamics of such populations. New interactions drawn from invading mutants can drive the population away from the previous equilibrium, and lead to changes in the population size -- the population size is an evolving property rather than a fixed number or externally controlled variable. We present analytical results for the average population size over time and quantify the extinction risk of the population by the mean time to extinction.

evolutionary biology↗

bioRxiv2018

Beyond type 1 regulatory T cells: co-expression of LAG3 and CD49b in IL-10-producing T cell lineages

Type 1 regulatory CD4+ T (Tr1) cells express high levels of the immunosuppressive cytokine IL-10 but not the master transcription factor Foxp3, and can suppress inflammation and promote immune tolerance. In order to identify and obtain viable Tr1 cells for research and clinical applications, co-expression of CD49b and LAG3 has been proposed as a unique surface signature for both human and mouse Tr1 cells. However, recent studies have revealed that this pattern of co-expression is dependent on the stimulating conditions and the differentiation stage of the CD4+ T cells. Here, using an IL-10GFP/Foxp3RFP dual reporter transgenic murine model, we demonstrate that co-expression of CD49b and LAG3 is not restricted to the Foxp3- Tr1 cells, but is also observed in Foxp3+ T regulatory (Treg) cells and CD8+ T cells that produce IL-10. Our data indicate that IL-10-producing Tr1 cells, Treg cells and CD8+ T cells are all capable of co-expressing LAG3 and CD49b in vitro following differentiation under IL-10-inducing conditions, and in vivo following pathogenic insult or infection in the pulmonary mucosa. Our findings urge caution in the use of LAG3/CD49b co-expression to identify Tr1 cells, since it may mark IL-10-producing T cell lineages more broadly, including the Foxp3- Tr1 cells, Foxp3+ Treg cells and CD8+ T cells.

immunology↗

bioRxiv2018

TCR/ITK signaling via mTOR tunes CD8+ T cell homeostatic proliferation, metabolism, and anti-tumor effector function

T cell homeostatic proliferation (HP) is regulated by T cell receptor (TCR) signals and homeostatic cytokines, and suggested to be proportional to TCR signal strength. However, we show here that ITK, a positive regulator of TCR signaling, negatively tunes CD8+ T cell HP, metabolism, and effector function. Under lymphopenic environments, Itk-/- CD8+ T cells exhibit significant increase in T cell-intrinsic HP, which requires mTOR activity and can be driven by T cell-T cell interaction. TCR signals through ITK tune IL-7-mediated CD8+ T cell metabolism and HP in a mTOR-dependent manner. The lack of ITK also resulted in enhanced effector cell fate programming, antigen sensitivity and anti-tumor immunity by HP cells. Thus, TCR signaling via ITK, is a negative tuner of CD8+ T cell homeostasis, metabolism and effector function, and may be a target for clinical benefit in cancer therapy.\n\nOne Sentence SummaryTCR signal strength had been long-thought to be proportional to T cell proliferation and effector function, here we demonstrate a counterintuitive role of the TCR signaling through ITK in negatively tuning proliferation under lymphopenic conditions via regulating mTOR activity, T cell metabolism, proliferation, and effector function.

immunology↗

bioRxiv2018

Zebrafish hhex null mutant develops an intrahepatic intestinal tube due to de-repression of cdx1b and pdx1

The hepatopancreatic duct (HPD) system links the liver and pancreas to the intestinal tube and is composed of the extrahepatic biliary duct, gallbladder and pancreatic duct. Haematopoietically-expressed-homeobox (Hhex) protein plays an essential role in the establishment of HPD, however, the molecular mechanism remains elusive. Here we show that zebrafish hhex-null mutants fail to develop the HPD system characterized by lacking the biliary marker Annexin A4 and the HPD marker sox9b. The mutant HPD system is replaced by an intrahepatic intestinal tube characterized by expressing the intestinal marker fatty-acid-binding-protein 2a (fabp2a). Cell lineage analysis showed that this intrahepatic intestinal tube is not originated from hepatocytes or cholangiocytes. Further analysis revealed that cdx1b and pdx1 were expressed ectopically in the intrahepatic intestinal tube and knockdown of cdx1b and pdx1 restored the expression of sox9b in the mutant. Chromatin-immunoprecipitation analysis shows that Hhex binds to the promoters of pdx1 and cdx1b genes to repress their expression. We therefore propose that Hhex, Cdx1b and Pdx1 form a genetic network governing the patterning and morphogenesis of the HPD and digestive tract systems in zebrafish.

developmental biology↗

bioRxiv2018

High-throughput identification and marker development of perfect SSR for cultivated genus of passion fruit (Passiflora edulis)

Simple sequence repeat (SSR) markers are characterized by high polymorphism, good reproducibility and co-dominance etc. They can be easily applied to develop efficient, simple and practical molecular markers. In the present study, bioinformatics methods were applied to identify high-throughput perfect SSRs of cultivar Passiflora genome. A total of 13104 perfect SSRs were obtained. SSR core sequence structure is mainly 2-4 bases, the maximum numbers are TA, AT, TC and AG. The maximum numbers of repetitions were up to 20 times. A total of 12934 pairs of SSR markers were developed by using bioinformatics software, and 20 pairs of markers were selected for amplification specificity assessment of MTX and WJ10, and the polymorphism rate was as high as 60%. The large-scale development of the SSR markers of Passiflora cultivar has paved a foundation for the efficient utilization of the germplasm resources of passion fruit, genetic improvement of the varieties and molecular breeding.

genomics↗

bioRxiv2018

Bacillus cereus HS24 Suppresses Conidia Germination of Magnaporthe oryzae by Inhibiting the Ca2+ Signaling Pathway

Rice yield is greatly reduced due to rice blast, a worldwide multi-cycle fungal disease caused by the ascomycete Magnaporthe oryzae. Previously, Bacillus cereus HS24 was isolated from rice growing area, which showed a strong bio-control effect on M. oryzae. In order to better exploit it as a bio-control agent, HS24 has been studied for its mechanism of controlling rice blast. Our results showed that conidial germination of M. oryzae was significantly inhibited by HS24 suspension, n and the inhibition rate reached to 97.83% at the concentration of 10 CFU/ml. The transcriptional level of CAMKII, PMC1 and CCH1, which are key genes involved in Ca2+ signaling pathway, were significantly decreased in HS24-treated conidia. The treatment of M. oryzae with Ca2+ signaling pathway inhibitors KN-93, Verapamil, and cyclopiazonic acid (CPA) significantly reduced conidial germination rate and inhibited germ tube elongation. This inhibition effect was found to be concentration-dependent, similar to the HS24 treatment. By quantifying free Ca2+ in M. oryzae conidia, a significant reduction of intracellular free Ca2+ concentration in HS24-treated conidia in comparison to sterile water-treated conidia was found. The addition of exogenous Ca2+ did not abolish the inhibitory effect of HS24 on the reduction of intracellular free Ca2+ concentration and conidial germination. In conclusion, B. cereus HS24 can inhibit conidial germination by suppressing Ca2+ signaling in M. oryzae, and thus offers a great potential as a bio-control agent in rice blast management.\n\nImportanceIn the bio-control of rice blast, most of researches focused on the inhibitory effect of bio-control agents on development of M. oryzae, including inhibition of conidia germination, germ tube deformity, mycelium growth inhibition, etc, while little work has elucidated the molecular mechanisms underlying the various phenotypic change in M. oryzae. In order to better exploit HS24 as a potential bio-control agent, we studied the molecular mechanisms underlying the suppression of B. cereus HS24 on M. oryzae Guy11, and draw the conclusion that HS24 may inhibit conidia germination and germ tube elongation through inhibiting the Ca2+ signaling pathway. In this study, we characterized the morphological and physiological changes of M. oryzae when interacting with B. cereus HS24, and further investgated the responses of M. oryzae Ca2+ signallig pathway to HS24 treatment. Thus we have provided one more piece for the B. cereus / M. oryzae supression puzzle at the molecular level.

microbiology↗

bioRxiv2018

Widespread and polymorphous noncoding amino acid residues in human sperm proteome

Proteins are usually deciphered by translation of the coding genome; however, their amino acid residues are seldom determined directly across the proteome. Herein, we describe a systematic workflow for identifying all possible protein residues that differ from the coding genome, termed noncoded amino acids (ncAAs). By measuring the mass differences between the coding amino acids and the actual protein residues in human spermatozoa, over a million nonzero delta masses were detected, fallen into 424 high-quality Gaussian clusters and 571 high-confidence ncAAs spanning 29,053 protein sites. Most ncAAs are novel with unresolved side-chains and discriminative between healthy individuals and patients with oligoasthenospermia. For validation, 40 out of 98 ncAAs that matched with amino acid substitutions were confirmed by exon sequencing. This workflow revealed the widespread existence of previously unreported ncAAs in the sperm proteome, which represents a new dimension on the understanding of amino acid polymorphisms at the proteomic level.\n\nHighlightsO_LI571 ncAAs spanning 108,000 protein sites were identified in human sperm proteome.\nC_LIO_LIMost ncAAs are novel with unresolved sidechains and found at unreported protein sites.\nC_LIO_LIExon sequencing confirmed 40 of 98 ncAAs that matched with amino acid substitutions.\nC_LIO_LIMany ncAAs are linked with disease and have potential for diagnosis and targeting.\nC_LI\n\neTOC BlurbWe describe a systematic identification of all possible protein residues that were not encoded by their genomic sequences. A total of 571 high-confidence most novel noncoded amino acids were identified in human sperm proteome, corresponding to over 108,000 ncAA-containing protein sites. For validation, 40 out of 98 ncAAs that matched to amino acid substitutions were confirmed by exon sequencing. These ncAAs are discriminative between individuals and expand our understanding of amino acid polymorphisms in human proteomes and diseases.

molecular biology↗