Biology subjects

Gong, J.

Publications and source records attributed to Gong, J..

At least 55 records · Page 3Linked to original sources

bioRxiv2020

SARS-CoV-2 manipulates the SR-B1-mediated HDL uptake pathway for its entry

The recently emerged pathogenic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread rapidly, leading to a global COVID-19 pandemic. Binding of the viral spike protein (SARS-2-S) to cell surface receptor angiotensin-converting enzyme 2 (ACE2) mediates host cell infection. In the present study, we demonstrate that in addition to ACE2, the S1 subunit of SARS-2-S binds to HDL and that SARS-CoV-2 hijacks the SR-B1-mediated HDL uptake pathway to facilitate its entry. SR-B1 facilitates SARS-CoV-2 entry into permissive cells by augmenting virus attachment. MAb (monoclonal antibody)-mediated blocking of SARS-2-S-HDL binding and SR-B1 antagonists strongly inhibit HDL-enhanced SARS-CoV-2 infection. Notably, SR-B1 is co-expressed with ACE2 in human pulmonary and extrapulmonary tissues. These findings revealed a novel mechanism for SARS-CoV-2 entry and could provide a new target to treat SARS-CoV-2 infection.

microbiology↗

bioRxiv2020

scGNN: a novel graph neural network framework for single-cell RNA-Seq analyses

Single-cell RNA-sequencing (scRNA-Seq) is widely used to reveal the heterogeneity and dynamics of tissues, organisms, and complex diseases, but its analyses still suffer from multiple grand challenges, including the sequencing sparsity and complex differential patterns in gene expression. We introduce the scGNN (single-cell graph neural network) to provide a hypothesis-free deep learning framework for scRNA-Seq analyses. This framework formulates and aggregates cell-cell relationships with graph neural networks and models heterogeneous gene expression patterns using a left-truncated mixture Gaussian model. scGNN integrates three iterative multi-modal autoencoders and outperforms existing tools for gene imputation and cell clustering on four benchmark scRNA-Seq datasets. In an Alzheimers disease study with 13,214 single nuclei from postmortem brain tissues, scGNN successfully illustrated disease-related neural development and the differential mechanism. scGNN provides an effective representation of gene expression and cell-cell relationships. It is also a novel and powerful framework that can be applied to scRNA-Seq analyses.

bioinformatics↗

bioRxiv2020

Digital spatial profiling of coronary plaques from persons living with HIV reveals high levels of STING and CD163 in macrophage enriched regions

BackgroundChronic innate and adaptive immune activation may contribute to high prevalence of cardiovascular disease in persons living with HIV (PLWH). MethodsWe assessed coronary plaques from deceased PLWH (n=6) and HIV-negative (n=6) persons matched by age and gender. Formalin-fixed, paraffin-embedded 5m thick sections were processed using Movat, hematoxylin and eosin, immunohistochemical and immunofluorescence stains. Immune cell populations were measured using surface antibodies, and immune-related protein expression from macrophage rich, T-cell rich and perivascular adipose tissue regions using GeoMx(R) digital spatial profiling. ResultsCoronary plaques from PLWH and HIV-negative persons had similar plaque area and percent stenosis. Percent CD163+ cells as measured by immunohistochemical staining was significantly higher in PLWH, median 0.29% (IQR 0.11-0.90) vs. 0.01% (IQR 0.0013-0.11) in HIV-negative plaque, p = 0.02 (Figure 1A). Other surface markers of innate cells (CD68 +, p=0.18), adaptive immune cells (CD3+, p=0.39; CD4+, p=0.09; CD8+, p=0.18) and immune trafficking markers (CX3CR1+, p=0.09) within the coronary plaque trended higher in HIV-positive plaques but did not reach statistical significance. GeoMx(R) digital spatial profiling showed higher differential protein expression of CD163 (scavenger receptor for hemoglobin-haptoglobin complex), stimulator of interferon gamma (STING, a cytosolic DNA sensor), CD25 and granzyme-B in the HIV-positive compared to HIV-negative, p<0.05(Figure 1B). O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=141 SRC="FIGDIR/small/221325v1_fig1.gif" ALT="Figure 1"> View larger version (51K): org.highwire.dtl.DTLVardef@1a4757forg.highwire.dtl.DTLVardef@1e2236org.highwire.dtl.DTLVardef@582f4borg.highwire.dtl.DTLVardef@188f376_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOFigure 1.C_FLOATNO Characterization of coronary plaques. Representative coronary plaques from three HIV-positive and three HIV-negative individuals were stained with H&E and Movat stain (A). Plaque area (m2) and % plaque stenosis were measured and calculated in 6 individuals per group (B). Statistical analysis, Mann-Whitney; ns not significant C_FIG ConclusionsIncreased inflammation within the coronary plaques of PLWH is characterized by more innate and adaptive immune cells. Higher STING expression in PLWH suggests that immune response to viral antigens within the plaque might be a driver above other stimulants. STING inhibitors are available and could be investigated as a future therapeutic target in PWH if these results are replicated with a larger number of plaques. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=146 SRC="FIGDIR/small/221325v1_ufig1.gif" ALT="Figure 1"> View larger version (42K): org.highwire.dtl.DTLVardef@27fa00org.highwire.dtl.DTLVardef@8e4a65org.highwire.dtl.DTLVardef@1b65320org.highwire.dtl.DTLVardef@10b7c9a_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIImmunohistochemical and fluorescent stains combined with GeoMx(R) digital spatial profiling allowed for deep characterization of immune cells within intact coronary plaques and perivascular adipose tissue C_LIO_LICoronary plaques from HIV-positive persons had higher proportion of CD163+ immune cells compared to HIV-negative persons C_LIO_LIDifferential protein expression of immune-rich regions of interest within intact 5m sections of coronary plaques revealed higher levels of stimulator of interferon gamma (STING) in HIV-positive persons C_LI

immunology↗

bioRxiv2020

An exploratory rehearsal on AIE dots assisted NIR-II fluorescence non-human primates imaging

Superb reliability and biocompatibility equip aggregation-induced emission (AIE) dots with tremendous potential for fluorescence bioimaging. However, there is still a chronic lack of design instructions of excretable and bright AIE emitters. Here, we designed a kind of PEGylated AIE (OTPA-BBT) dots with strong absorption and extremely high NIR-II PLQY as 13.6%, and proposed the long-aliphatic-chain design blueprint contributing to their excretion from animal body. Assisted by the OTPA-BBT dots with bright fluorescence beyond 1100 nm and even 1500 nm (NIR-IIb), large-depth cerebral vasculature (beyond 600 m) as well as real-time blood flowing were monitored through-thinned-skull, and noninvasive NIR-IIb imaging with rich high-spatial-frequency information gave a precise presentation of gastrointestinal tract in marmosets. Importantly, after intravenous or oral administration, the definite excretion of OTPA-BBT dots from the body was demonstrated, which showed an influential evidence of bio-safety.

bioengineering↗

bioRxiv2020

An Arabidopsis gene expression predictor enables inference of transcriptional regulators

Gene expression regulation by transcription factors (TF) has long been studied, but no model exists yet that can accurately predict transcriptome profiles based on TF activities. We have constructed a universal predictor for Arabidopsis to predict the expression of 28192 non-TF genes using 1678 TFs. Applied to bulk RNA-Seq samples from diverse tissues, the predictor produced accurate predicted transcriptomes correlating well with actual expression, with average correlation coefficient of 0.986. Having recapitulated the quantitative relationships between TFs and target genes, the predictor further enabled downstream inference of TF regulators for genes and pathways, i.e. those involved in suberin, flavonoid, glucosinolate metabolism, lateral root, xylem, secondary cell wall development, and endoplasmic reticulum stress response. Our predictor provides an innovative approach to study transcriptional regulation.

systems biology↗

bioRxiv2020

Decoding transcriptional regulation via a human gene expression predictor

Transcription factors (TF) regulate cellular activities via controlling gene expression, but a predictive model describing how TFs quantitatively modulate human transcriptomes was lacking. We constructed a universal human gene expression predictor and utilized it to decode transcriptional regulation. Using 1613 TFs expression, the predictor reconstituted highly accurate transcriptomes for samples derived from a wide range of tissues and conditions. The predictors broad applicability indicated it had recapitulated the quantitative relationships between TFs and target genes ubiquitous across tissues. Significant interacting TF-target gene pairs were then extracted from the predictor and enabled downstream inference of TF regulators for diverse pathways involved in development, immunity, metabolism, and stress response. Thus, we present a novel approach to study human transcriptional regulation following the "understanding by modeling" principle.

systems biology↗

bioRxiv2020

Orthogonal genome-wide screenings in bat cells identify MTHFD1 as a target of broad antiviral therapy

Bats are responsible for the zoonotic transmission of several major viral diseases including the 2003 SARS outbreak and the ongoing COVID-19 pandemic. While bat genomic sequencing studies have revealed characteristic adaptations of the innate immune system, functional genomic studies are urgently needed to provide a foundation for the molecular dissection of the tolerance of viral infections in bats. Here we report the establishment and screening of genome-wide RNAi library and CRISPR library for the model megabat, Pteropus Alecto. We used the complementary RNAi and CRISPR libraries to interrogate Pteropus Alecto cells for infection with two different viruses, mumps virus and Influenza A virus, respectively. Screening results converged on the endocytosis pathway and the protein secretory pathway as required for both viral infections. Additionally, we revealed a general dependence of the C-1-tetrahydrofolate synthase gene, MTHFD1, for viral replication in bat cells as well as in human cells. MTHFD1 inhibitor carolacton potently blocked replication of several RNA viruses including SARS-CoV-2. Our studies provide a resource for systematic inquiry into the genetic underpinnings of bat biology and a potential target for developing broad spectrum antiviral therapy.

microbiology↗

bioRxiv2020

New intranuclear symbiotic bacteria from macronucleus of Paramecium putrinum -- Candidatus Gortzia yakutica

Holospora-like bacteria are obligate intracellular Alphaproteobacteria, inhabiting nuclei of Paramecium ciliates and other protists. Alphaproteobacteria have drawn significant attention, as both closest existing relatives of bacteria that gave rise to mitochondria, as well as a class of intracellular bacteria with numerous important pathogens. HLB clade includes two genera - Holospora (Hafkine 1980) and candidatus Gortzia (Boscaro 2013). These bacteria have a peculiar life cycle with two morphological forms, a strict specificity to the host species and the type of nucleus they inhabit. Here we describe a new species of HLB - candidatus Gortzia yakutica sp. nov., a symbiont from macronucleus of Paramecium putrinum, the first known HLB for this Paramecium species. The new symbiont shows morphological similarities with other HLB. The phylogenetic analysis of SSU rDNA gene places it into candidatus Gortzia clade.

microbiology↗

bioRxiv2020

LocusFocus: A web-based colocalization tool for the annotation and functional follow-up of GWAS

Genome-wide association studies (GWAS) have primarily identified trait-associated loci in the non-coding genome. Colocalization analyses of SNP-level associations from GWAS with expression quantitative trait loci (eQTL) evidence enable the generation of hypotheses about responsible mechanism, genes and tissues of origin to guide functional characterization. Here, we present a web-based colocalization browsing and testing tool named LocusFocus (https://locusfocus.research.sickkids.ca). LocusFocus formally tests colocalization using our established Simple Sum method to identify the most relevant genes and tissues for a particular GWAS locus in the presence of high linkage disequilibrium and/or allelic heterogeneity. Full documentation and source code for LocusFocus are publicly available.

genomics↗

bioRxiv2019

DNB-Based On-Chip Motif Finding (DocMF): a High-Throughput Method to Profile Different Types of Protein-DNA Interactions

Here we report a highly sensitive DNB-based on-chip Motif Finding (DocMF) system that utilizes high throughput next-generation-sequencing (NGS) chips to profile protein binding or cleaving activity. Using DocMF, we successfully identified a variety of endonuclease recognition sites and the protospacer-adjacent-motif (PAM) sequences of different CRISPR systems. Our DocMF platform can simultaneously screen both 5 and 3 PAM regions with high coverage using the same NGS library/chip. For the well-studied SpCas9, our DocMF platform identified a small proportion of noncanonical 5-NAG-3 ([~]5%) and 5-NGA-3 ([~]1.6%), in addition to its common PAMs, 5-NGG-3 ([~]89.9%). We also used the DocMF to assay two uncharacterized Cas endonucleases, VeCas9 and BvCpf1. VeCas9 PAMs were not detected by the conventional PAM depletion method. However, DocMF discovered that both VeCas9 and BvCpf1 required broader and more complicated PAM sequences for target recognition. VeCas9 preferred the R-rich motifs, whereas BvCpf1 used the T-rich PAMs. Moreover, after slightly changing the experimental protocol, we observed that dCas9, a DNA-binding protein lacking endonuclease activity, preferably binded to the previously reported PAMs 5-NGG-3. In summary, our studies demonstrate that DocMF is the first tool with the capacity to exhaustively assay both the binding and the cutting properties of different DNA-binding proteins.

molecular biology↗

bioRxiv2019

Patterned Neuronal Activities Dictate Cell Type-specific Axon Regeneration

Why closely related neuronal types differ in their axon regenerative abilities remains elusive. Here, we demonstrate gliotransmission determines such a difference in Drosophila larval sensory neurons. Axotomy activates ensheathing glia, which signal to regenerative neurons through the gliotransmitter adenosine, to mount regenerative programs including neuronal activity and Ras. Surprisingly, ensheathing glia do not signal to non-regenerative neurons. Such neuronal type-specific responses to gliotransmission result from specific expression of adenosine receptors in regenerative neurons. Disrupting gliotransmission impedes regeneration of regenerative neurons. Strikingly, reconstitution of gliotransmission in non-regenerative neurons enables them to regenerate. Furthermore, activation of an adenosine receptor ortholog in adult mice promotes both regeneration and survival of retinal ganglion cells, uncovering a conserved pro-regenerative role of adenosine receptors. Our studies demonstrate gliotransmission as a novel mechanism by which glia instruct axon regeneration, with neuronal type-specificity, and suggest targeting purinergic signaling as a new strategy for mammalian central nervous system repair. HIGHLIGHTSEnsheathing glia differentially interact with Drosophila sensory neuron types through gliotransmission Gliotransmission mounts axon regenerative programs in selective neuronal types Neuronal firing pattern but not overall excitability dictates axon regeneration outcome Adenosine receptor activation in adult mice promotes both regeneration and survival of RGCs

neuroscience↗

bioRxiv2019

Genome-wide quantitative trait loci mapping on Verticilliumw

Cotton Verticillium wilt (VW) is a devastating disease seriously affecting fiber yield and quality, and the most effective and economical prevention measure at present is selection and extension of Gossypium varieties harboring high resistant VW. However, multiple attempts to improve the VW resistance of the most widely cultivated Upland cotton have brought in little significant progress, and it seems necessary and urgent to develop Chromosome segment substitution lines (CSSLs) for merging the superior genes related with high yield and wide adaptation from G. hirsutum and VW resistance and excellent fiber quality from G. barbadense. In this study, 300 CSSLs were chosen from the developed BC5F3:5 CSSLs constructed by G. hirsutum CCRI36 and G. barbadense Hai1 to conduct quantitative trait locus (QTL) mapping on VW resistance, and a total of 53 QTLs relevant to VW disease index (DI) were identified together with the phenotypic data of 2 years investigations in two fields with two replications per year. All the QTLs were distributed on 20 chromosomes with phenotypic variation of 3.74-11.89%, of which 29 stable ones were consistent in at least two environments. Based on Meta-analysis on the 53 QTLs, 43 novel ones were identified, while 10 ones consistent to previously identified QTLs. Meanwhile, 32 QTL hotspot regions were detected, including 15 ones were novel. This study concentrates on QTL identification and screening hotspot region related with VW in the 300 CSSLs, which lay a solid platform not only for revealing the genetic and molecular mechanisms of VW resistance, but also for further fine mapping, gene cloning and molecular designing in breeding program for resistant cotton varieties.

plant biology↗

bioRxiv2019

Objects seen as scenes: neural circuitry for attending whole or parts

Depending on our goals, we pay attention to the global shape of an object or to the local shape of its parts, since its difficult to do both at once. This typically effortless process can be impaired in disease. However, it is not clear which cortical regions carry the information needed to constrain shape processing to a chosen global/local level. Here, novel stimuli were used to dissociate functional MRI responses to global and local shapes. This allowed identification of cortical regions containing information about level (independent from shape). Crucially, these regions overlapped part of the cortical network implicated in scene processing. As expected, shape information (independent of level) was mainly located in category-selective areas specialized for object- and face-processing. Regions with the same informational profile were strongly linked (as measured by functional connectivity), but were weak when the profiles diverged. Specifically, in the ventral-temporal-cortex (VTC) regions favoring level and shape were consistently separated by the mid-fusiform sulcus (MFS). These regions also had limited crosstalk despite their spatial proximity, thus defining two functional pathways within VTC. We hypothesize that object hierarchical level is processed by neural circuitry that also analyses spatial layout in scenes, contributing to the control of the spatial-scale used for shape recognition. Use of level information tolerant to shape changes could guide whole/part attentional selection but facilitate illusory shape/level conjunctions under impoverished vision. Significance statementOne daily engages hierarchically organized objects (e.g. face-eyes-eyelashes). Their perception is commonly studied with global shapes composed by of local shapes. Seeing shape at one level is easy, but difficult for both at once. How can the brain guide attention to one level? Here using novel stimuli that dissociate different levels over time and examining local patterns of brain-activity, we found that the level and shape of visual objects were represented into segregated sets of cortical regions, each connected into their own pathway. Level information was found in part of the cortical network known to process scenes. Coding of object-level independently from shape could participate in guiding sustained attention within objects, eliminating interference from irrelevant levels. It could also help produce "illusory conjunctions" (perceptual migration of a shape to the wrong level) when attention is limited. HighlightsO_LIModified Navon figures allow dissociation in time of fMRI responses for the global/local levels. C_LIO_LIShape-invariant hierarchical level information was found in scenes selective areas, whereas level-invariant shape information was found in object- and faces- selective areas. C_LIO_LILevel and shape regions were divided by the mid-fusiform sulcus (MFS) in VTC cortex, and each type of region connected into its own pathway. C_LIO_LIHaving separate level/shape pathways could facilitate selective-attention, but foster illusory conjunctions. C_LI

neuroscience↗

bioRxiv2019

Defining the microenvironment landscape of bladder cancer using highly multiplexed spatial genomic and proteomic analysis

Muscle-invasive bladder cancer (MIBC) is an aggressive disease with limited therapeutic options. PD-1 pathway targeting immunotherapies have been approved to treat advanced bladder cancer, but most patients exhibit primary resistance, suggesting that immune evasion mechanisms exist. The PPAR{gamma} pathway has been identified as a potential therapeutic target in MIBC that is associated with reduced CD8+ T-cell infiltration and increased resistance to immunotherapies. We comprehensively profiled the tumor microenvironment (TME) in formalin-fixed, paraffin-embedded (FFPE) tissues from a cohort of PPAR{gamma}high (n=13) and PPRAR{gamma}low (n=12) MIBC, integrating bulk gene expression, targeted mutation sequencing, immunohistochemistry and multiplex spatial profiling of RNA and protein expression on the GeoMx Digital Spatial Profiling (DSP) platform. Molecular subtyping was consistent between traditional methods and GeoMx profiling, and, in this cohort, we observed little evidence of spatial heterogeneity in tumor subtyping. The previously characterized T-cell exclusion phenotype of PPAR{gamma}high MIBC was recapitulated on the GeoMx platform and was further extended to show that this is a general phenomenon across immune cell types, supporting potential combination of PPAR{gamma} inhibition with ICIs. Furthermore, we found that while immune cells were excluded from PPAR{gamma}high tumors, the stromal compartment from these tumors was not significantly different than those PPAR{gamma}low tumors. By preserving spatial relationships during the GeoMx analysis, we also identify a novel association between lower immune cell expression in the tumors and higher expression of {beta}-catenin in the stroma, and differential expression of other WNT pathway members associated with PPAR{gamma} activity.\n\nOne Sentence SummaryA new method for capturing tumor-immune signaling in FFPE tissues explores how the PPARG signaling axis is associated with immune cell exclusion in bladder cancer.

cancer biology↗

bioRxiv2019

Gene modules associated with human diseases revealed by network analysis

Despite many genes associated with human diseases have been identified, disease mechanisms often remain elusive due to the lack of understanding how disease genes are connected functionally at pathways level. Within biological networks, disease genes likely map to modules whose identification facilitates etiology studies but remains challenging. We describe a systematic approach to identify disease-associated gene modules. A gene co-expression network based on the graphical Gaussian model (GGM) was constructed using the GTEx dataset and assembled into 652 gene modules. Screening these modules identified those with disease genes enrichment for obesity, cardiomyopathy, hypertension, and autism, which illuminated the molecular pathways underlying their pathogenesis. Using mammalian phenotypes derived from mouse models, potential disease candidate genes were identified from these modules. Also analyzed were epilepsy, schizophrenia, bipolar disorder, and depressive disorder, revealing shared and distinct disease modules among brain disorders. Thus, disease genes converge on modules within our GGM gene co-expression network, which provides a general framework to dissect genetic architecture of human diseases.

systems biology↗

bioRxiv2018

VIKNGS: A C++ VARIANT INTEGRATION KIT FOR NEXTGENERATION SEQUENCING ASSOCIATION ANALYSIS

MotivationIntegration of next generation sequencing data (NGS) across different research studies can improve the power of genetic association testing by increasing sample size and can obviate the need for sequencing controls. Unfortunately, if differential genotype uncertainty across studies is not accounted for, combining data sets can also produce spurious association results. The robust variance score statistic (RVS) for genetic association of rare and common variants has been shown to effectively adjust for bias caused by the differences in read depth in case-control genetic association studies when the two groups were sequenced using different experimental designs. To enable consortium research, the aggregation of several data sets for genetic association analysis of quantitative and binary traits with covariate adjustment is required, and we developed the Variant Integration Kit for NGS (VikNGS) that expands the functionality of RVS (vRVS) for this purpose.\n\nResultsVikNGS is a fast and computationally efficient cross-platform software package that provides an implementation for vRVS, as well as conventional rare and common variant genotype-based association analysis approaches. The package includes a graphical user interface that contains power simulation functionality and data visualization tools.\n\nAvailability and ImplementationThe VikNGS package can be downloaded at http://www.tcag.ca/tools/index.html\n\nDocumentation can be found at https://VikNGSdocs.readthedocs.io/en/latest/\n\nContactlisa.strug@sickkids.ca\n\nSupplementary informationSupplementary data are available at Bioinformatics online.

genetics↗

bioRxiv2018

Haplotype Analysis of the TRB Locus by TCRB Repertoire Sequencing

Polymorphism within the T cell receptor beta variable gene (TRBV) has been implicated in autoimmune disease and immuneCrelated adverse events (IRAEs) during immunotherapy. Previous efforts to evaluate TRBV polymorphism by whole genome sequencing (WGS) have been hampered by the repetitive nature of the TCRB locus. We present a novel longCamplicon TCRB repertoire sequencing approach to evaluate TRBV polymorphism from peripheral blood, which we use to identify TRBV allele haplotypes in 81 Caucasians.

immunology↗

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↗