Biology subjects

Liu, G.

Publications and source records attributed to Liu, G..

At least 235 records · Page 13Linked to original sources

bioRxiv2020

neoDL: A novel neoantigen intrinsic feature-based deep learning model identifies IDH wild-type glioblastomas with the longest survival

BackgroundIDH wild-type glioblastoma (GBM) is the most aggressive tumor in the central nervous system in spite of extensive therapies. Neoantigen based personalized immune therapies achieve promising results in melanoma and lung cancer, but few neoantigen based models perform well in IDH wild-type GBM. Unlike the neoantigen load and occurrence that are well studied and often found useless, the association between neoantigen intrinsic features and prognosis remain unclear in IDH wild-type GBM. ResultsWe presented a novel neoantigen intrinsic feature-based deep learning model (neoDL) to stratify IDH wild-type GBMs into subgroups with different survivals. We first calculated a total of 2928 intrinsic features for each neoantigen and filtered out those not associated with survival, followed by applying neoDL in the TCGA data cohort. Leave one out cross validation (LOOCV) in the TCGA demonstrated that neoDL successfully classified IDH wild-type GBMs into different prognostic subgroups, which was further validated in an independent data cohorts from Asian population. Long-term survival IDH wild-type GBMs identified by neoDL were found characterized by 12 protective neoantigen intrinsic features and enriched in development and cell cycle. ConclusionsOur results provide a novel model, neoDL, that can be therapeutically exploited to identify IDH wild-type GBM with good prognosis who will most likely benefit from neoantigen based personalized immunetherapy.

bioinformatics↗

bioRxiv2020

Identification of four linear B-cell epitopes on the SARS-CoV-2 spike protein able to elicit neutralizing antibodies

SARS-CoV-2 unprecedentedly threatens the public health at worldwide level. There is an urgent need to develop an effective vaccine within a highly accelerated time. Here, we present the most comprehensive S-protein-based linear B-cell epitope candidate list by combining epitopes predicted by eight widely-used immune-informatics methods with the epitopes curated from literature published between Feb 6, 2020 and July 10, 2020. We find four top prioritized linear B-cell epitopes in the hotspot regions of S protein can specifically bind with serum antibodies from horse, mouse, and monkey inoculated with different SARS-CoV-2 vaccine candidates or a patient recovering from COVID-19. The four linear B-cell epitopes can induce neutralizing antibodies against both pseudo and live SARS-CoV-2 virus in immunized wild-type BALB/c mice. This study suggests that the four linear B-cell epitopes are potentially important candidates for serological assay or vaccine development.

microbiology↗

bioRxiv2020

Type VI secretion system killing by commensal Neisseria is influenced by the spatial dynamics of bacteria

Type VI Secretion Systems (T6SS) are widespread in bacteria and can dictate the development and organisation of polymicrobial ecosystems by mediating contact dependent killing. In Neisseria species, including Neisseria cinerea a commensal of the human respiratory tract, interbacterial contacts are mediated by Type four pili (Tfp) which promote formation of aggregates and govern the spatial dynamics of growing Neisseria microcolonies. Here we show that N. cinerea expresses a plasmid-encoded T6SS that is active and can limit growth of related pathogens. We explored the impact of Tfp expression on N. cinerea T6SS-dependent killing and show that expression of Tfp by prey strains enhances their susceptibility to T6SS, by keeping them in close proximity of T6SS-wielding attacker strains. Our findings have important implications for understanding how spatial constraints during contact-dependent antagonism can shape the evolution of microbial communities.

microbiology↗

bioRxiv2020

Characterization of the first cultured free-living representative of Candidatus Izimaplasma uncovers its unique biology

Candidatus Izimaplasma, an intermediate in the reductive evolution from Firmicutes to Mollicutes, was proposed to represent a novel class of free-living wall-less bacteria within the phylum Tenericutes found in deep-sea methane seeps. Unfortunately, the paucity of marine isolates currently available has limited further insights into their physiological and metabolic features as well as ecological roles. Here, we present a detailed description of the phenotypic traits, genomic data and central metabolisms tested in both laboratorial and deep-sea environments of the novel strain zrk13, which allows for the first time the reconstruction of the metabolic potential and lifestyle of a member of the tentatively defined Candidatus Izimaplasma. On the basis of the description of strain zrk13, the novel species and genus Xianfuyuplasma coldseepsis is proposed. Notably, DNA degradation driven by X. coldseepsis zrk13 was detected in both laboratorial and in situ conditions, strongly indicating it is indeed a key DNA degrader. Moreover, the putative genes determining degradation broadly distribute in the genomes of other Izimaplasma members. Given extracellular DNA is a particularly crucial phosphorus as well as nitrogen and carbon source for microorganisms in the seafloor, Izimaplasma bacteria are thought to be important contributors to the biogeochemical cycling in the deep ocean.

microbiology↗

bioRxiv2020

BMSCs differentiated into neurons, astrocytes and oligodendrocytesalleviatedthe inflammation and demyelination of EAE mice models

Multiple sclerosis (MS) is a complex, progressive neuroinflammatory disease associated with autoimmunity. Currently, effective therapeutic strategy was poorly found in MS. Experimental autoimmune encephalomyelitis (EAE) is widely used to study the pathogenesis of MS. Previous studies have shown that bone marrow mesenchymal stem Cells (BMSCs) transplantation could treat EAE animal models, but the mechanism was divergent. Here, we systematically evaluated whether BMSCs can differentiate into neurons, astrocytes and oligodendrocytes to alleviate the symptoms of EAE mice. We used Immunofluorescence staining to detect MAP-2 neurons marker, GFAP astrocytes marker, and MBP oligodendrocytes marker expression to evaluate whether BMSCs can differentiate. The effect of BMSCs transplantation on inflammatory cell invasion and demyelination in EAE mice were detected by Hematoxylin-Eosin (H&E) and Luxol Fast Blue (LFB) staining. Inflammatory factors expression was detected by ELISA and RT-qPCR. Our results showed that BMSCs could be induced to differentiate into neuron cells, astrocytes and oligodendrocyte in vivo and in vitro. In addition, BMSCs transplant improved the survival rate and weight, and reduced neurological function scores and disease incidence of EAE mice. Moreover, BMSCs transplant alleviated the inflammation and demyelination of EAE mice. Finally, we found that BMSCs transplantation down-regulated the expression levels of pro-inflammatory factors TNF-, IL-1{beta} and IFN-{gamma}, and up-regulated the expression levels of anti-inflammatory factors IL-10 and TGF-{beta}. In conclusion, this study found that BMSCs could alleviate the inflammatory response and demyelination in EAE mice, which may be achieved by the differentiation of BMSCs into neurons, astrocytes and oligodendrocytes in EAE mice.

neuroscience↗

bioRxiv2020

Comparative genomic analyses provide clues to capsule switch in Streptococcus suis

Streptococcus suis (S. suis) is a major bacterial pathogen in swine industry and also an emerging zoonotic agent. S. suis produces an important extracellular component, capsular polysaccharides (CPS). Based on which, dozens of serotypes have been identified. Through virulence genotyping, we uncovered the relatedness between proportions of SS2, SS3 and SS7 strains despite their differences in serotypes. Multi-locus sequence typing (MLST) was used to characterize whole S. suis population, revealing that there is capsule switch between S. suis strains. Importantly, capsule switch occurred in SS2, 3 and 7 strains belonging to CC28 and CC29, which is phylogenetically distinct from the main CC1 SS2 lineage. To further explore capsule switch in S. suis, comparative genomic analyses were performed using available S. suis complete genomes. Phylogenetic analyses suggested that SS2 strains can be divided into two clades (1 and 2), and those classified into clade 2 are colocalized with SS3 and SS7 strains, which is in accordance with above virulence genotyping and MLST analyses. Clade 2 SS2 strains presented high genetic similarity with SS3 and SS7 and shared common competence and defensive elements, but are significantly different from Clade 1 SS2 strains. Notably, although the cps locus shared by Clade 1 and 2 SS2 strains is almost the same, a specific region in cps locus of strain NSUI002 (Clade 2 SS2) can be found in SS3 cps locus, but not in Clade 1 SS2 strain. These data indicated that SS2 strains appeared in CC28 and CC29 might acquire cps locus through capsule switch, which could well explain the distinction of genetic lineages within SS2 population.

microbiology↗

bioRxiv2020

Xingnaojing injection can regulate dysbacteriosis and increase the concentration of short chain fatty acids in the feces after stroke in mice

BackgroundXingnaojing injection (XNJ) is extracted from the Chinese ancient prescription "An-Gong-Niu-Huang Pill", is widely used for stroke in China. We mainly observe the effect of XNJ (Xingnaojing) injection on the gut microbiota in stroke model mice. MethodsForty-two 7-to 8-week-old male C57 mice weighing 22-24 g were chosen for the experiment. There were 6 mice in each group; the 7 groups were the normal group (NG), the MCAO group (CG), the MCAO+XNJ group (EG), the sham surgery group (SG), the sham germ-free normal group (SGFNG), the sham germ-free+MCAO group (SGFCG), and the sham germ-free+MCAO+XNJ group (SGFEG). Two days before modeling, we abdominally administered Xingnaojing (6 mg/kg) the SGFEG and EG groups. The processing time of sustained XNJ was 5 days. Three days after modeling, 1 ~ 2 mouse feces were collected, and after a MiSeq PE library was constructed, an Illumina MiSeq PE 300 platform was used for high-throughput sequencing. After cleaning the sequencing data, the microbiome and microbiomeseq packages were used for analysis using R software (version 3.6.2). ResultsAlpha diversity analysis revealed that the diversity was not different between the CG and EG. The Simpson index was different between the SGFCG and SGFEG. XNJ increased the levels of Sutterellaceae and decreased the level of Deferribacteres and Morganella. LEfSe analysis showed that SGFCG mice were also enriched with Morganella. XNJ increased the concentrations of the SCFAs PA (propionate), VA (valerate), IBA (isobutyrate), and IVA (isovalerate) in the feces of the SGFEG group. BA (butyrate) had greater positive correlation with gut bacteria than other acids in the SGFCG, and XNJ changed this trend. KEGG analysis showed that peptidoglycan biosynthesis was most different between the CG and EG. ConclusionIschemic stroke (IS) causes dysbiosis of some specific bacteria in the gut microbiota in MCAO mice. Xingnaojing ameliorated this condition by increasing the levels of Sutterellaceae and decreasing the level of Deferribacteres and Morganella. These results are in accordance with other research on Chinese medicines for IS that affect the gut microbiota. Enrichment analysis of SCFAs revealed that XNJ improved the levels of SCFAs through an energy metabolism-related pathway.

bioinformatics↗

bioRxiv2020

Bacteroidetes contribute to the carbon and nutrient cycling of deep sea through breaking down diverse glycans

Bacteroidetes are thought to be specialized for the degradation of algae-derived ocean polysaccharides and are a major contributor to the marine carbon and nutrient cycling. Here, we first show Bacteroidetes are the second most abundant phylum bacteria in deep-sea cold seep and possess more genes associated with polysaccharides degradation than other bacteria through metagenomics methods. We further isolate a novel Bacteroidetes species, Maribellus comscasis WC007T, which can efficiently degrade numerous different polysaccharides including: cellulose, pectin, fucoidan, mannan, xylan and starch. These results are verified by transcriptomic analyses and growth assays. Notably, we find cellulose promotes abundant bacterial growth, and using transcriptomics and metabolomics we finally report on the underlying mechanisms of cellulose degradation and utilization, as well as potential contributions to the carbon cycling. Overall, our results suggest Bacteroidetes play key roles in the deep-sea carbon and nutrient cycling, likely due to their high abundance and prominent polysaccharide degradation capabilities. One Sentence SummaryBacteroidetes contribute to ocean carbon and nutrient cycle.

microbiology↗

bioRxiv2020

A deep learning framework with hybrid encoding for protein coding regions prediction in biological sequences

Protein coding regions prediction is a very important but overlooked subtask for tasks such as prediction of complete gene structure, coding/noncoding RNA. Many machine learning methods have been proposed for this problem, they first encode a biological sequence into numerical values and then feed them into a classifier for final prediction. However, encoding schemes directly influence the classifiers capability to capture coding features and how to choose a proper encoding scheme remains uncertain. Recently, we proposed a protein coding region prediction method in transcript sequences based on a bidirectional recurrent neural network with non-overlapping 3-mer feature, and achieved considerable improvement over existing methods, but there is still much room to improve the performance. First, 3-mer feature that counts the occurrence frequency of trinucleotides in a biological sequence only reflect local sequence order information between the most contiguous nucleotides, which loses almost all the global sequence order information. Second, kmer features of length k larger than three (e.g., hexamer) may also contain useful information. Based on the two points, we here present a deep learning framework with hybrid encoding for protein coding regions prediction in biological sequences, which effectively exploit global sequence order information, non-overlapping gapped kmer (gkm) features and statistical dependencies among coding labels. 3-fold cross-validation tests on human and mouse biological sequences demonstrate that our proposed method significantly outperforms existing state-of-the-art methods.

bioinformatics↗

bioRxiv2020

ISG15-dependent Activation of the RNA Sensor MDA5 and its Antagonism by the SARS-CoV-2 papain-like protease

Activation of the RIG-I-like receptors, RIG-I and MDA5, establishes an antiviral state by upregulating interferon (IFN)-stimulated genes (ISGs). Among these is ISG15 whose mechanistic roles in innate immunity still remain enigmatic. Here we report that ISGylation is essential for antiviral IFN responses mediated by the viral RNA sensor MDA5. ISG15 conjugation to the caspase activation and recruitment domains of MDA5 promotes the formation of higher-order assemblies of MDA5 and thereby triggers activation of innate immunity against a range of viruses including coronaviruses, flaviviruses and picornaviruses. The ISG15-dependent activation of MDA5 is antagonized through direct de-ISGylation mediated by the papain-like protease (PLpro) of SARS-CoV-2, a recently emerged coronavirus that causes the COVID-19 pandemic. Our work demonstrates a crucial role for ISG15 in the MDA5-mediated antiviral response, and also identifies a novel immune evasion mechanism of SARS-CoV-2, which may be targeted for the development of new antivirals and vaccines to combat COVID-19.

immunology↗

bioRxiv2020

Leukemia stemness and co-occurring mutations drive resistance to IDH inhibitors in acute myeloid leukemia

Allosteric inhibitors of mutant IDH1 or IDH2 induce terminal differentiation of the mutant leukemic blasts and provide durable clinical responses in approximately 40% of acute myeloid leukemia (AML) patients with the mutations. However, primary resistance and acquired resistance to the drugs are major clinical issues. To understand the molecular underpinnings of clinical resistance to IDH inhibitors (IDHi), we performed multipronged genomic analyses (DNA sequencing, RNA sequencing and cytosine methylation profiling) in longitudinally collected specimens from 68 IDH1- or IDH2-mutant AML patients treated with the inhibitors. The analysis revealed that leukemia stemness is a major driver of primary resistance to IDHi, whereas selection of mutations in RUNX1/CEBPA or RAS-RTK pathway genes was the main driver of acquired resistance to IDHi, along with BCOR, homologous IDH gene, and TET2. These data suggest that targeting stemness and certain high-risk co-occurring mutations may overcome resistance to IDHi in AML.

cancer biology↗

bioRxiv2020

MiRNA-223 Inhibits MouseGallstone Formation by Targeting Key Transporters in Hepatobiliary Cholesterol Secretion Pathway

BackgroudMiRNA-223 has previously been reported to play an essential role in hepatic cholesterol homeostasis by suppressing cholesterol synthesis, attenuating cholesterol uptake by hepatocyte from and promoting cholesterol efflux into the blood. However, its role in regulation of biliary cholesterol secretion and gallstone formation remains unknown. MethodsMice with conventional knockout (KO), hepatocyte-specific knockout ({Delta}Hepa) / knockdown (KD) or gain expression of miRNA-223 were included in the study and were subjected to lithogenic diet (LD) for various weeks. The gallbladders were harvested and subjected to cholesterol crystal imaging and gallstone mass measurement. Liver tissues were collected for western blotting, RT-qPCR, and immunohistochemistry staining. Levels of cholesterol, bile salt, phospholipids, and triglyceride were determined in serum, liver tissues, and bile by enzyme color reactive assays. 3 UTR reporter gene assays were used to verify the direct target genes for miRNA-223. ResultsLD-induced gallstone formation was remarkably accelerated in miRNA-223 KO, {Delta}Hepa, and KD mice with concurrent enhancement in total cholesterol levels in liver tissue and bile. Key biliary cholesterol transporters ABCG5 and ABCG8 were identified as direct targets of miRNA-223. Reversely, AAV-mediated hepatocyte-specific miRNA-223 overexpression prevented gallstone progression with reduced targets protein expression. ConclusionThe present study demonstrates a novel role of miRNA-223 in the regulation of hepatic bile cholesterol secretion pathway and gallstone formation by targeting ABCG5 and ABCG8 expression. Therefore, elevating miRNA-223 would be a potentially novel approach to overcome the sternness of cholesterol gallstone disease. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=173 SRC="FIGDIR/small/344580v1_ufig1.gif" ALT="Figure 1"> View larger version (36K): org.highwire.dtl.DTLVardef@1c418bforg.highwire.dtl.DTLVardef@134e20dorg.highwire.dtl.DTLVardef@e4e0d2org.highwire.dtl.DTLVardef@641b40_HPS_FORMAT_FIGEXP M_FIG C_FIG

pathology↗

bioRxiv2020

Subcellular relocalization and nuclear redistribution of the RNA methyltransferases TRMT1 and TRMT1L upon neuronal activation

RNA modifications are dynamic chemical entities that regulate RNA fate, and an avenue for environmental response in neuronal function. However, which RNA modifications may be playing a role in neuronal plasticity and environmental responses is largely unknown. Here we characterize the biochemical function and cellular dynamics of two human RNA methyltransferases previously associated with neurological dysfunction, TRMT1 and its homolog, TRMT1-like (TRMT1L). Using a combination of next-generation sequencing, LC-MS/MS, patient-derived cell lines and knockout mouse models, we confirm the previously reported dimethylguanosine (m 2,2 G) activity of TRMT1 in tRNAs, as well as reveal that TRMT1L, whose activity was unknown, is responsible for methylating a subset of cytosolic tRNA Ala (AGC) isoacceptors at position 26. Using a cellular in vitro model that mimics neuronal activation and long term potentiation, we find that both TRMT1 and TRMT1L change their subcellular localization upon neuronal activation. Specifically, we observe a major subcellular relocalization from mitochondria and other cytoplasmic domains (TRMT1) and nucleoli (TRMT1L) to different small punctate compartments in the nucleus, which are as yet uncharacterized. This phenomenon does not occur upon heat shock, suggesting that the relocalization of TRMT1 and TRMT1L is not a general reaction to stress, but rather a specific response to neuronal activation. Our results suggest that subcellular relocalization of RNA modification enzymes play a role in neuronal plasticity and transmission of information, presumably by addressing new targets.

molecular biology↗

bioRxiv2020

Efficient Multiplex Genome Editing Tools Identified by Protoplast Technology in Phalaenopsis

Phalaenopsis orchids are popular ornamental plants worldwide. The application of the efficient multiplex genome editing tools in Phalaenopsis, will greatly accelerate the development of orchid gene function and breeding research. In this study, we establish a fast and convenient Phalaenopsis protoplast platform for the identification of functional genome editing tools. Two multiplex genome editing tools, PTG-Cas9 (PTG, polycistronic tRNA gRNA) system and PTGm-Cas9 (PTG-Cas9 system with modified sgRNA structure) system are designed to edit PDS gene of commercial Phalaenopsis ST166 at four target sites. We find that both PTG-Cas9 and PTGm-Cas9 system are functional in Phalaenopsis, and the PTGm-Cas9 system with modified sgRNA has a higher editing efficiency than PTG-Cas9 system. Further, we design another multiplex genome editing tool, termed as DPII-Cpf1 system (dual Pol II promoter to drive the expression of Cpf1 endonuclease and crRNA), to edit PDS gene of Phalaenopsis at four target sites likewise. All the four targets are efficiently edited by DPII-Cpf1 system, and the total mutation rate is about 3 times higher than that of PTGm-Cas9 system. Taken together, using the Phalaenopsis protoplast platform, we successfully establish two efficient multiplex genome editing tools for Phalaenopsis research, PTGm-Cas9 and DPII-Cpf1. The multiplex genome editing tools established in this study have great application potentials in efficiently constructing large-scale knockout mutant libraries of orchid and speeding up orchid precise breeding.

plant biology↗

bioRxiv2020

Vitexin inhibited the invasion, metastasis, and progression of human melanoma cells by targeting STAT3 signaling pathway

In human melanoma cells, resistance to conventional chemotherapy and radiotherapy and rapid metastasis give melanoma a remarkable feature of the most aggressive and lethal. The low response rate of melanoma to existing treatment modalities is a substantial threat to patients and researchers. It is crucial to identify new therapeutic agents for the fatal malignancy melanoma. Vitexin is a flavonoid compound in many traditional Chinese medicines that exhibits antioxidant, anti-inflammatory and anti-tumour activities in many cancer cells. In our study, we elucidated the inhibitory effects of vitexin on invasion and metastasis in human melanoma A375 and C8161 cells in vitro. After vitexin treatment for 24 h or 48 h, the invasive ability and migration of melanoma cells were decreased in a dose- and time-dependent manners. In western blot analysis, we verified that vitexin inhibited the expression levels of MMP-2, MMP-9, vimentin, Slug and Twist which are known as the regulators of protein degradation and promote various cell behaviours such as migration and invasion. To further investigate the target signal that may be influenced by vitexin, immunofluorescence assay was performed to observe STAT3 localization and western blot results showed that vitexin decreased the expression of the phosphorylation of kinases that inducing STAT3 activation. Accordingly, we provide inspiring insight into the basic inhibition mechanism of vitexin, which will soon be an issue due to its scientific potential for further development as a novel anti-tumour agent for the clinical therapy of human melanoma.

cancer biology↗

bioRxiv2020

Mouse Single Pancreatic β Cell Transcriptomics Reveal Sexual Dimorphism of Transcriptomes and Identify Sex-dependent Type 2 Diabetes Altered Genes

Type 2 diabetes (T2D), characterized by malfunction of pancreatic {beta} cells, is affected by multiple cues including sex differences. Nevertheless, mechanisms of sex differences in type 2 diabetes susceptibility and pathogenesis remain unclear. Using single-cell RNA sequencing (scRNA-seq) technology, we showed that sexual dimorphism of transcriptome exists in mouse {beta} cells. Our analysis further revealed the existence of sex-dependent type 2 diabetes altered genes in high fat diet induced T2D model, suggesting divergences in pathological mechanisms of type 2 diabetes between sexes. Our results indicated that sex should be taken into consideration when treating diabetes, which was further validated by the sex-matched and sex-mismatched islet transplantation in mice. Compared to sex-matched transplants, sex-mismatched transplants showed downregulation of genes involved in the longevity regulating pathway in {beta} cells and led to impaired glucose tolerance in diabetic mice. Taken together, our findings could advance current understanding of type 2 diabetes pathogenesis with sexually dimorphic perspectives and provide new insights to the development of precision medicine.

bioinformatics↗

bioRxiv2020

A common binding motif in the ET domain of BRD3 forms polymorphic structural interfaces with host and viral proteins

The extra-terminal (ET) domain of BRD3 is conserved among BET proteins (BRD2, BRD3, BRD4), interacting with multiple host and viral protein-protein networks. Solution NMR structures of complexes formed between BRD3-ET domain with either the 79-residue murine leukemia virus integrase (IN) C-terminal domain (IN329-408), or its 22-residue IN tail peptide (TP) (IN386-407) alone, reveal similar intermolecular three-stranded {beta}-sheet formation. 15N relaxation studies reveal a 10-residue linker region (IN379-388) tethering the SH3 domain (IN329-378) to the ET-binding motif (IN389-405)-ET complex. This linker has restricted flexibility, impacting its potential range of orientations in the IN - nucleosome complex. The complex of the ET-binding peptide of host NSD3 protein (NSD3148-184) and BRD3-ET domain includes a similar three-stranded {beta}-sheet interaction, but the orientation of the {beta}-hairpin is flipped compared to the two IN : ET complexes. These studies expand our understanding of molecular recognition polymorphism in complexes of ET-binding motifs with viral and host proteins. HighlightsO_LIThe BRD3 ET domain binds to key peptide motifs of diverse host and viral proteins. C_LIO_LIThese complexes reveal conformational plasticity in molecular recognition. C_LIO_LINMR studies demonstrate restricted interdomain motion in the IN CTD / ET complex. C_LIO_LIA cost-effective approach is described for producing isotopically-labeled peptides. C_LI Etoc BlurbWe address structurally how the MLV Integrase (IN) usurps the host function of the BET protein through comparative studies of the IN : Brd3 ET complex with that of the host NSD3. MLV integration and thus its pathogenesis is driven through protein interactions of the IN : BET family.

microbiology↗

bioRxiv2020

KuLGaP: A Selective Measure for Assessing Therapy Response in Patient-Derived Xenografts

Quantifying response to drug treatment in mouse models of human cancer is important for treatment development and assignment, and yet remains a challenging task. A preferred measure to quantify this response should take into account as much of the experimental data as possible, i.e. both tumor size over time and the variation among replicates. We propose a theoretically grounded measure, KuLGaP, to compute the difference between the treatment and control arms. KuLGaP is more selective than currently existing measures, reduces the risk of false positive calls and improves translation of the lab results to clinical practice.

bioinformatics↗