Biology subjects

Xu, D.

Publications and source records attributed to Xu, D..

At least 217 records · Page 12Linked to original sources

bioRxiv2020

AI-aided design of novel targeted covalent inhibitors against SARS-CoV-2

The focused drug repurposing of known approved drugs (such as lopinavir/ritonavir) has been reported failed for curing SARS-CoV-2 infected patients. It is urgent to generate new chemical entities against this virus. As a key enzyme in the life-cycle of coronavirus, the 3C-like main protease (3CLpro or Mpro) is the most attractive for antiviral drug design. Based on a recently solved structure (PDB ID: 6LU7), we developed a novel advanced deep Q-learning network with the fragment-based drug design (ADQN-FBDD) for generating potential lead compounds targeting SARS-CoV-2 3CLpro. We obtained a series of derivatives from those lead compounds by our structure-based optimization policy (SBOP). All the 47 lead compounds directly from our AI-model and related derivatives based on SBOP are accessible in our molecular library at https://github.com/tbwxmu/2019-nCov. These compounds can be used as potential candidates for researchers in their development of drugs against SARS-CoV-2.

pharmacology and toxicology↗

bioRxiv2020

Functional specialization of human salivary glands and origins of proteins intrinsic to human saliva

Salivary proteins are essential for maintaining health in the oral cavity and proximal digestive tract and serve as a diagnostic window into human disease. However, their precise organ origins remain unclear. Through transcriptomic analysis of major adult and fetal salivary glands, and integration with the saliva proteome and transcriptomes of 28+ organs, we linked human saliva proteins to their source, identified salivary gland-specific genes, and uncovered fetal- and adult-specific gene repertoires. Our results also provide new insights into the degree of gene retention during maturation and suggest that functional diversity between adult gland-types is driven by specific dosage combinations of hundreds of transcriptional regulators rather than a few gland-specific factors. Finally, we demonstrate the hitherto unrecognized heterogeneity of the human acinar cell lineage. Our results pave the way for future investigations into glandular biology and pathology, as well as salivas use as a diagnostic fluid.

developmental biology↗

bioRxiv2020

The transmembrane serine protease inhibitors are potential antiviral drugs for 2019-nCoV targeting the insertion sequence-induced viral infectivity enhancement

At the end of 2019, the SARS-CoV-2 induces an ongoing outbreak of pneumonia in China1, even more spread than SARS-CoV infection2. The entry of SARS-CoV into host cells mainly depends on the cell receptor (ACE2) recognition and spike protein cleavage-induced cell membrane fusion3,4. The spike protein of SARS-CoV-2 also binds to ACE2 with a similar affinity, whereas its spike protein cleavage remains unclear5,6. Here we show that an insertion sequence in the spike protein of SARS-CoV-2 enhances the cleavage efficiency, and besides pulmonary alveoli, intestinal and esophagus epithelium were also the target tissues of SARS-CoV-2. Compared with SARS-CoV, we found a SPRR insertion in the S1/S2 protease cleavage sites of SARS-CoV-2 spike protein increasing the cleavage efficiency by the protein sequence aligment and furin score calculation. Additionally, the insertion sequence facilitates the formation of an extended loop which was more suitable for protease recognition by the homology modeling and molicular docking. Furthermore, the single-cell transcriptomes identified that ACE2 and TMPRSSs are highly coexpressed in AT2 cells of lung, along with esophageal upper epithelial cells and absorptive enterocytes. Our results provide the bioinformatics evidence for the increased spike protein cleavage of SARS-CoV-2 and indicate its potential target cells.

microbiology↗

bioRxiv2020

The digestive system is a potential route of 2019-nCov infection: a bioinformatics analysis based on single-cell transcriptomes

Since December 2019, a newly identified coronavirus (2019 novel coronavirus, 2019-nCov) is causing outbreak of pneumonia in one of largest cities, Wuhan, in Hubei province of China and has draw significant public health attention. The same as severe acute respiratory syndrome coronavirus (SARS-CoV), 2019-nCov enters into host cells via cell receptor angiotensin converting enzyme II (ACE2). In order to dissect the ACE2-expressing cell composition and proportion and explore a potential route of the 2019-nCov infection in digestive system infection, 4 datasets with single-cell transcriptomes of lung, esophagus, gastric, ileum and colon were analyzed. The data showed that ACE2 was not only highly expressed in the lung AT2 cells, esophagus upper and stratified epithelial cells but also in absorptive enterocytes from ileum and colon. These results indicated along with respiratory systems, digestive system is a potential routes for 2019-nCov infection. In conclusion, this study has provided the bioinformatics evidence of the potential route for infection of 2019-nCov in digestive system along with respiratory tract and may have significant impact for our healthy policy setting regards to prevention of 2019-nCoV infection.

microbiology↗

bioRxiv2020

Hesperetin inhibits foam cell formation in macrophages via activating LXRα signal in an AMPK dependent manner

Cholesterol efflux from macrophages is the first step of cholesterol reverse transport (RCT), whose increase inhibits cholesterol accumulation and foam cell formation to suppress atherogenesis. Liver X receptor alpha (LXR) and adenosine monophosphate activated protein kinases (AMPK) both have the pivotal role in cholesterol homeostasis. However the association between these two molecules in cell model of atherosclerosis is poorly understood. Hesperetin has been reported to possess several protective effects for cardiovascular diseases, while little is known about the role of hesperetin and its underlying mechanism on macrophage foam cell formation. In this study, we sought to investigate the potential effects of hesperetin in cholesterol efflux by using human macrophage derived foam cells, focusing on liver X receptor alpha (LXR) and adenosine monophosphate activated protein kinases (AMPK) implication. Hesperetin treatment concentration-dependently reduced foam cell formation, intracellular cholesterol level and cholesterol esterification rate, and enhanced cholesterol efflux in THP-1 macrophages. Hesperetin upregulated the protein levels of LXR and its targets including ABCA1, ABCG1 as well as SR-BI, and phosphorylated-AMPK. Meanwhile, hesperetin-induced upregulation of LXR expression was enhanced by AMPK agonist and inhibited by AMPK inhibitor. Furthermore, hesperetin increased mRNA level of LXR and its target genes, all which were depressed by AMPK1/2 small interfering RNA (siRNA) transfection. In conclusion, we founded for the first time that hesperetin could active AMPK. And this activation upregulated LXR and its targets including ABCA1, ABCG1 and SR-BI, which significantly inhibited foam cell formation and promoted cholesterol efflux in THP-1 macrophages. Our results highlight the therapeutic potential of hespretin for the possible reduction in foam cell formation. This new mechanism could contribute the anti-atherogenic effects of hesperetin.

pharmacology and toxicology↗

bioRxiv2019

A genetic map of the response to DNA damage in human cells

The response to DNA damage is critical for cellular homeostasis, tumor suppression, immunity and gametogenesis. In order to provide an unbiased and global view of the DNA damage response in human cells, we undertook 28 CRISPR/Cas9 screens against 25 genotoxic agents in the retinal pigment epithelium-1 (RPE1) cell line. These screens identified 840 genes whose loss causes either sensitivity or resistance to DNA damaging agents. Mining this dataset, we uncovered that ERCC6L2, which is mutated in a bone-marrow failure syndrome, codes for a canonical non-homologous end-joining pathway factor; that the RNA polymerase II component ELOF1 modulates the response to transcription-blocking agents and that the cytotoxicity of the G-quadruplex ligand pyridostatin involves trapping topoisomerase II on DNA. This map of the DNA damage response provides a rich resource to study this fundamental cellular system and has implications for the development and use of genotoxic agents in cancer therapy.

cancer biology↗

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

A functional cortical network for sensorimotor sequence generation

The brain generates complex sequences of movements that can be flexibly reconfigured in real-time based on sensory feedback, but how this occurs is not fully understood. We developed a novel sequence licking task in which mice directed their tongue to a target that moved through a series of locations. Mice could rapidly reconfigure the sequence online based on tactile feedback. Closed-loop optogenetics and electrophysiology revealed that tongue/jaw regions of somatosensory (S1TJ) and motor (M1TJ) cortex encoded and controlled tongue kinematics at the level of individual licks. Tongue premotor (anterolateral motor, ALM) cortex encoded intended tongue angle in a smooth manner that spanned individual licks and even whole sequences, and progress toward the reward that marked successful sequence execution. ALM activity regulated sequence initiation, but multiple cortical areas collectively controlled termination of licking. Our results define a functional cortical network for hierarchical control of sensory- and reward-guided orofacial sequence generation.

neuroscience↗

bioRxiv2019

Cell growth kinetics and accumulation of secondary metabolite of Bletilla striata Rchb.f. using cell suspension culture

Bletilla striata (Orchidaceae) is a well-recognized endangered medicinal plant due to inadequate natural reproduction with high market worth. To evaluate the cell growth kinetics and accumulation of secondary metabolites (SMs), the cell suspension culture is proved to be a valuable approach for acquiring the high yield of medicinal parts. An effective cell suspension culture for obtaining B. striata cell growth and its SMs was in vitro induction of callus from B. striata seeds. The cell growth kinetics and accumulation of SMs were analyzed using the mathematical model. Results cell growth kinetic model revealed that the growth curve of B. striata suspension cells was curved as sigmoid shape, indicating the changes of the growth curve of suspension cells. Improved Murashige and Skoog cell growth medium was the utmost favorable medium for B. striata callus formation with the highest cell growth during the stationary phase of cultivation period, the cell growth acceleration was started after 7 days and thereafter gradually decrease at 24 day and then reached to highest at 36 day of cultivation period in both dry weight and fresh weight. The coelonin concentration was peak during exponential growth stage and decreased afterward at the stationary phase in the cell suspension culture. The maximum content of coelonin (about 0.3323 mg/g cell dry weight) was observed on the 18th day of the cultivation cycle while the dactylorhin A and militarine reached highest at 24 day, and p-hydroxybenzyl alcohol at 39 day. This investigation also laid a foundation for multi-mathematical model to better describe the accumulation variation of SMs. The production of SMs had shown great specificity during cells growth and development. This research provided a well-organized way to more accumulation and production of SMs, on scale-up biosynthesis in B. striata cell suspension culture.

plant biology↗

bioRxiv2019

CD155/CD96 promotes immunosuppression in lung adenocarcinoma (LUAD)

Lung adenocarcinoma (LUAD) remains one of the leading causes of death in patients with cancer. The association of CD155 with CD96 transmits an inhibitory signal and suppresses antitumor immune response. This study investigates the effect of CD155/CD96 on immune suppression in LUAD. We demonstrate that LUAD patients with high CD155 expression suffer from immune suppression and experience a poor prognosis, which coincides with an inhibited AKT-mTOR signaling pathway in CD8 T cells and subsequently up-regulated CD96 expression. Moreover, the inhibition effect can be reversed by CD96 blocking antibody. High CD155 expression inhibited the release of IFN{gamma} from CD8 cells. Moreover, Blocking CD96 restored IFN{gamma} production in CD8 T cells and neutralized the inhibition of IFN{gamma} production in CD8 T cells mediated by CD155. Animal experiments showed that CD155-mediated LUAD growth might depend on its suppression antitumor immune response in the tumor microenvironment in PDX mice. In conclusion, our results suggest that LUAD cells suppress antitumor immune response in the tumor microenvironment through CD155/CD96. CD155/CD96 could be a potential therapeutic target for LUAD patients.\n\nAbbreviationsLUAD: lung adenocarcinoma; IFN{gamma}: interferon gamma; PDX: patient-derived xenograft; NSCLC: non-small cell lung cancer; PRR: poliovirus receptor-related; MDSCs: myeloid-derived suppressor cells; PRR: poliovirus receptor-related; STR: short tandem repeat; IRS: immunoreactive score; SI: staining intensity; PP: percentage of positive cells; RT-PCR: reverse transcription-polymerase chain reaction; PBS: phosphate-buffered saline; PBMCs: peripheral blood mononuclear cells; SDS-PAGE: sodium dodecyl sulfate-polyacrylamide gel electrophoresis; rCD155: recombinant human CD155; LUAD cells: lung adenocarcinoma cells; TILs: tumor-infiltrating lymphocytes; GzmB: granzyme B; IL-2 (Interleukin-2); TNF- : tumor necrosis factor-alpha; PI: propidium Iodide; PDX: patient-derived xenograft; TIGIT: T cell immunoreceptor with Igand ITIM domains; WBC: white blood cells; MFI: mean fluorescence intensity; HPF: high power field

cancer biology↗

bioRxiv2019

Neural Multi-Scale Self-Supervised Registration for Echocardiogram Dense Tracking

Echocardiography has become routinely used in the diagnosis of cardiomyopathy and abnormal cardiac blood flow. However, manually measuring myocardial motion and cardiac blood flow from echocar-diogram is time-consuming and error-prone. Computer algorithms that can automatically track and quantify myocardial motion and cardiac blood flow are highly sought after, but have not been very successful due to noise and high variability of echocardiography. In this work, we propose a neural multi-scale self-supervised registration (NMSR) method for automated myocardial and cardiac blood flow dense tracking. NMSR incorporates two novel components: 1) utilizing a deep neural net to parameterize the velocity field between two image frames, and 2) optimizing the parameters of the neural net in a sequential multi-scale fashion to account for large variations within the velocity field. Experiments demonstrate that NMSR yields significantly better registration accuracy than the state-of-the-art methods, such as advanced normalization tools (ANTs) and Voxel Morph, for both myocardial and cardiac blood flow dense tracking. Our approach promises to provide a fully automated method for fast and accurate analyses of echocardiograms.

bioengineering↗

bioRxiv2019

Loss-of-function tolerance of enhancers in the human genome

Previous studies have surveyed the potential impact of loss-of-function (LoF) variants and identified LoF-tolerant protein-coding genes. However, the tolerance of human genomes to losing enhancers has not yet been evaluated. Here we present the catalog of LoF-tolerant enhancers using structural variants from whole-genome sequences. Using a conservative approach, we estimate that each individual human genome possesses at least 28 LoF-tolerant enhancers on average. We assessed the properties of LoF-tolerant enhancers in a unified regulatory network constructed by integrating tissue-specific enhancers and gene-gene interactions. We find that LoF-tolerant enhancers are more tissue-specific and regulate fewer and more dispensable genes. They are enriched in immune-related cells while LoF-intolerant enhancers are enriched in kidney and brain/neuronal stem cells. We developed a supervised learning approach to predict the LoF-tolerance of enhancers, which achieved an AUROC of 96%. We predict 5,677 more enhancers would be likely tolerant to LoF and 75 enhancers that would be highly LoF-intolerant. Our predictions are supported by known set of disease enhancers and novel deletions from PacBio sequencing. The LoF-tolerance scores provided here will serve as an important reference for disease studies.

genomics↗

bioRxiv2019

A candidate causal variant underlying both higher intelligence and increased risk of bipolar disorder

Bipolar disorder is a highly heritable mental illness, but the relevant genetic variants and molecular mechanisms are largely unknown. Recent GWASs have identified an intergenic region associated with both cognitive performance and bipolar disorder. This region contains dozens of putative fetal brain-specific enhancers and is located [~]0.7 Mb upstream of the neuronal transcription factor POU3F2. We identified a candidate causal variant, rs77910749, that falls within a highly conserved putative enhancer, LC1. This human-specific variant is a single-base deletion in a PAX6 binding site and is predicted to be functional. We hypothesized that rs77910749 alters LC1 activity and hence POU3F2 expression during neurodevelopment. Indeed, transgenic reporter mice demonstrated LC1 activity in the developing cerebral cortex and amygdala. Furthermore, ex vivo reporter assays in embryonic mouse brain and human iPSC-derived cerebral organoids revealed increased enhancer activity conferred by the variant. To probe the in vivo function of LC1, we deleted the orthologous mouse region, which resulted in amygdala-specific changes in Pou3f2 expression. Lastly, humanized rs77910749 knock-in mice displayed behavioral defects in sensory gating, an amygdala-dependent endophenotype seen in patients with bipolar disorder. Our study suggests a molecular mechanism underlying the long-speculated link between enhanced cognitive performance and neuropsychiatric disease.

genetics↗

bioRxiv2018

Differential phase partition of a PICS complex is required for piRNA processing and chromosome segregation in C. elegans

Piwi-interacting RNAs (piRNAs) play significant roles in suppressing transposons and non-self nucleic acids, maintaining genome integrity, defending against viral infections, and are essential for fertility in a variety of organisms. In C. elegans, most piRNA precursors are transcribed by RNA polymerase II in the nucleus and are subjected to a number of processing and maturation steps. However, the biogenesis of piRNAs are still not fully understood. We used functional proteomics to study piRNA biogenesis in C. elegans and identified a PICS complex that is required for piRNA processing and chromosome segregation. The PICS complex contains two known piRNA biogenesis factors TOFU-6 and PID-1, and three new proteins PICS-1, TOST-1, and ERH-2, which exhibit dynamic localization among different subcellular compartments. In the germline of gravid animals, the PICS complex contains TOFU-6/PICS-1/ERH-2/PID-1 and largely concentrate at the perinuclear granule zone and engages in piRNA processing. During early embryogenesis, the TOFU-6/PICS-1/ERH-2/TOST-1 complex accumulates in the nucleus and play essential roles in chromosome segregation and cell division. Interestingly, the function of these factors in mediating chromosome segregation is independent of piRNA production. Therefore, we speculate that a differential phase partition of PICS factors may help cells to coordinate distinct cellular processes.

genetics↗

bioRxiv2018

Proteomic Profile of TGF-β1 treated Lung Fibroblasts identifies Novel Markers of Activated Fibroblasts in the Silica Exposed Rat Lung

We performed liquid chromatography-tandem mass spectrometry (LC-MS/MS) on control and TGF-{beta}1-exposed rat lung fibroblasts to identify proteins differentially expressed between cell populations. A total of 1648 proteins were found to be differentially expressed in response to TGF-{beta}1 treatment and 196 proteins were expressed at [≥] 1.2 fold relative to control. Guided by these results, we next determined whether similar changes in protein expression were detectable in the rat lung after chronic exposure to silica dust. Of the five proteins selected for further analysis, we found that levels of all proteins were markedly increased in the silica-exposed rat lung, including the proteins for the very low density lipoprotein receptor (VLDLR) and the transmembrane (type I) heparin sulfate proteoglycan called syndecan 2 (SDC2). Because VLDLR and SDC2 have not, to our knowledge, been previously linked to the pathobiology of silicosis, we next examined whether knockdown of either gene altered responses to TGF-{beta}1 in MRC-5 lung fibroblasts. Interestingly, we found knockdown of either VLDLR or SDC2 dramatically reduced collagen production to TGF-{beta}1, suggesting that both proteins might play a novel role in myofibroblast biology and pathogenesis of silica-induced pulmonary fibrosis. In summary, our findings suggest that performing LC-MS/MS on TGF-{beta}1 stimulated lung fibroblasts can uncover novel molecular targets of activated myofibroblasts in silica-exposed lung.\n\nHighlightsWe identified 196 proteins differentially expressed between control and TGF-{beta}1 treated fibroblastsby LC-MS/MS.\n\nSeveral proteins identified by LC-MS/MS were also found to be differentially expressed in whole lung tissues and isolated fibroblasts after chronic exposure to silica dust, including the very low density lipoprotein receptor (VLDLR) and the transmembrane type I heparan sulfate proteoglycan called syndecan 2\n\nKnockdown of SDC2 or VLDLR markedly inhibited collagen production in MRC-5 fibroblasts, suggesting a novel pathogenic role for these proteins in myofibroblast biology.

pharmacology and toxicology↗

bioRxiv2018

What can facial mechanoreceptors tell the mouse brain about whisking?

Haptic perception synthesizes touch with proprioception, or sense of body position. Humans and mice alike experience rich active touch of the face. Because most facial muscles lack proprioceptor endings, the sensory basis of facial proprioception remains unsolved. Facial proprioception may instead rely on mechanoreceptors that encode both touch and self-motion. In rodents, whisker mechanoreceptors provide a signal that informs the brain about whisker position. Whisking involves coordinated orofacial movements, so mechanoreceptors innervating facial regions other than whiskers could also provide information about whisking. To define all sources of sensory information about whisking available to the brain, we recorded spikes from mechanoreceptors innervating diverse parts of the face. Whisker motion was encoded best by whisker mechanoreceptors, but also by those innervating whisker pad hairy skin and supraorbital vibrissae. Redundant self-motion responses may provide the brain with a stable proprioceptive signal despite mechanical perturbations such as whisker growth and active touch.

neuroscience↗

bioRxiv2018

Reliable Multiplex Sequencing with Rare Index Mis-Assignment on DNB-Based NGS Platform

BackgroundMassively-parallel-sequencing, coupled with sample multiplexing, has made genetic tests broadly affordable. However, intractable index mis-assignments (commonly exceeds 1%) were repeatedly reported on some widely used sequencing platforms.\n\nResultsHere, we investigated this quality issue on BGI sequencers using three library preparation methods: whole genome sequencing (WGS) with PCR, PCR-free WGS, and two-step targeted PCR. BGIs sequencers utilize a unique DNB technology which uses rolling circle replication for DNA-nanoball preparation; this linear amplification is PCR free and can avoid error accumulation. We demonstrated that single index mis-assignment from free indexed oligos occurs at a rate of one in 36 million reads, suggesting virtually no index hopping during DNB creation and arraying. Furthermore, the DNB-based NGS libraries have achieved an unprecedentedly low sample-to-sample mis-assignment rate of 0.0001% to 0.0004% under recommended procedures.\n\nConclusionsSingle indexing with DNB technology provides a simple but effective method for sensitive genetic assays with large sample numbers.

genomics↗

bioRxiv2018

Validation of Prostate Cancer Risk Variants by CRISPR/Cas9 Mediated Genome Editing

GWAS have identified numerous SNPs associated with prostate cancer risk. One such SNP is rs10993994. It is located in the MSMB promoter, associates with MSMB encoded {beta}-microseminoprotein prostate secretion levels, and is associated with mRNA expression changes in MSMB and the adjacent gene NCOA4. In addition, our previous work showed a second SNP, rs7098889, is in LD with rs10993994 and associated with MSMB expression independent of rs10993994. Here, we generate a series of clones with single alleles removed by double guide RNA (gRNA) mediated CRISPR/Cas9 deletions, through which we demonstrate that each of these SNPs independently and greatly alters MSMB expression in an allele-specific manner. We further show that these SNPs have no substantial effect on the expression of NCOA4. These data demonstrate that a single SNP can have a large effect on gene expression and illustrate the importance of functional validation to deconvolute observed correlations. The method we have developed is generally applicable to test any SNP for which a relevant heterozygous cell line is available.\n\nAuthor summaryIn pursuing the underlying biological mechanism of prostate cancer pathogenesis, scientists utilized the existence of common single nucleotide polymorphisms (SNPs) in human genome as genetic markers to perform large scale genome wide association studies (GWAS) and have so far identified more than a hundred prostate cancer risk variants. Such variants provide an unbiased and systematic new venue to study the disease mechanism, and the next big challenge is to translate these genetic associations to the causal role of altered gene function in oncogenesis. The majority of these variants are waiting to be studied and lots of them may act in oncogenesis through gene expression regulation. To prove the concept, we took rs10993994 and its linked rs7098889 as an example and engineered single cell clones by allelic-specific CRISPR/Cas9 deletion to separate the effect of each allele. We observed that a single nucleotide difference would lead to surprisingly high level of MSMB gene expression change in a gene specific and tissue specific manner. Our study strongly supports the notion that differential level of gene expression caused by risk variants and their associated genetic locus play a major role in oncogenesis and also highlights the importance of studying the function of MSMB encoded {beta}-MSP in prostate cancer pathogenesis.

genetics↗