Biology subjects

Lin, Y.

Publications and source records attributed to Lin, Y..

At least 379 records · Page 21Linked to original sources

bioRxiv2020

Crystallization and preliminary X-ray diffraction studies of melibiose permease

Our work presented here showed that MelB can be crystallized in the conditions as similar as that of other membrane transporter protein of known structure. To identify a rigid protein by modifying the protein structure is the critical factor for facilitating MelB crystallization. It is necessary to perform extensive crystallization screens to obtain crystals. MelB-MelB interaction in the DDM containing solution will be affect by protein preparation, which may lead to reduce in reproducibility of crystallization experiment. Using a detergent mixture is essential for improve protein contact in the crystals, then improve crystallizability. R149C MelB crystal can be obtained in DDM, but these crystals were only diffracted to about 8Å resolution limit. MelB wide type crystal also can be obtained from the condition as that of R149C mutant, but the resolution is weaker than that of mutant. Although MelB and other transporters of known structure share common feature of the crystallization, the emphasis was as much on the protein itself, as it was on detergent type or efficient screening and refinement of the crystallization conditions.Competing Interest StatementThe authors have declared no competing interest.View Full Text

cancer biology↗

bioRxiv2020

NMDA receptors control cortical axonal projections via EPHRIN-B/EPHB signaling

Callosal projections from primary somatosensory cortex (S1) are key for processing somatosensory inputs and integrating sensory-motor information. How the callosal innervation pattern in S1 is formed during early postnatal development is not clear. We found that the normal termination pattern of these callosal projections is disrupted in cortex specific NMDAR mutants. Rather than projecting selectively to the primary/secondary somatosensory cortex (S1/S2) border, axons were uniformly distributed throughout S1. In addition, the density of this projection increased over postnatal life until the mice died by P30. By combining genetic and antibody-mediated loss of function, we demonstrated that it is NR2B-containing NMDA receptors in target S1 that mediate this guidance phenotype, thus playing a central role in interhemispheric connectivity. Furthermore, we found that this function of NMDA receptors in callosal circuit formation is independent of ion channel function and instead depends on interactions with EPHRIN-B/EPHB. Thus, NMDAR cooperates with EPHRIN-B/EPHB in target S1 to control the formation callosal circuits by acting as an accessory axon guidance receptor modulating EPH-dependent repulsion.

neuroscience↗

bioRxiv2020

Alteration of Substrate-Induced Conformational Changes of Escherichia coli Melibiose Permease by Mutating Arg149

Fourier transform infrared difference spectroscopy and fluorescence spectroscopic techniques have been used to obtain information about substrate-induced structural changes of the melibiose permease mutant R149C, compared with the Cys-less, which were reconstituted into liposomes. ATR-FTIR evidences show that Na+-induced difference spectra of R149C and Cys-less are similar. However, Na+ induces some new peaks for R149C mutant permease. This means that replacement of Arg-149 by Cys may affect the structure of MelB, and then affect the binding of Na+. Melibiose-induced difference spectra of R149C in the presence of Na+ show some peaks in the amide I region not seen in Cys-less, corresponding to turns, {beta}-sheets, -helix changes. This suggests that R149C mutant permease undergo some different secondary structure changes compared to Cys-less mutant permease, when binding melibiose. Comparison of the permease intrinsic fluorescence variations of R149C and Cys-less indicate that there are similar substrate binding properties between R149C and Cys-less. When analyzing the effects of different sugars it appears that the R149C mutant is more sensitive to the sugar. All these data indicate that replacement of Arg-149 by Cys will affect Na+ and sugar binding, and enhance the selectivity and sensitivity to sugars.

biochemistry↗

bioRxiv2020

Kmer2SNP: reference-free SNP calling from raw reads based on matching

The development of DNA sequencing technologies provides the opportunity to call heterozygous SNPs for each individual. SNP calling is a fundamental problem of genetic analysis and has many applications, such as gene-disease diagnosis, drug design, and ancestry inference. Reference-based SNP calling approaches generate highly accurate results, but they face serious limitations especially when high-quality reference genomes are not available for many species. Although reference-free approaches have the potential to call SNPs without using the reference genome, they have not been widely applied on large and complex genomes because existing approaches suffer from low recall/precision or high runtime. We develop a reference-free algorithm Kmer2SNP to call SNP directly from raw reads. Kmer2SNP first computes the k-mer frequency distribution from reads and identifies potential heterozygous k-mers which only appear in one haplotype. Kmer2SNP then constructs a graph by choosing these heterozygous k-mers as vertices and connecting edges between pairs of heterozygous k-mers that might correspond to SNPs. Kmer2SNP further assigns a weight to each edge using overlapping information between heterozygous k-mers, computes a maximum weight matching and finally outputs SNPs as edges between k-mer pairs in the matching. We benchmark Kmer2SNP against reference-free methods including hybrid (assembly-based) and assembly-free methods on both simulated and real datasets. Experimental results show that Kmer2SNP achieves better SNP calling quality while being an order of magnitude faster than the state-of-the-art methods. Kmer2SNP shows the potential of calling SNPs only using k-mers from raw reads without assembly. The source code is freely available at https://github.com/yanboANU/Kmer2SNP.

bioinformatics↗

bioRxiv2020

Gene expression and chromatin accessibility during progressive EMT and MET linked to dynamic CTCF engagement

BackgroundEpithelial-mesenchymal transition (EMT) facilitates cellular movements critical for proper development; however, in a carcinoma, EMT promotes metastatic dissemination. Stable intermediate states (partial-EMT) are increasingly implicated in metastatic dissemination while reversal of EMT, termed mesenchymal-epithelial transition (MET), is increasingly implicated in metastatic colonization. To understand the partial and reversible nature of EMT, we characterized chromatin accessibility dynamics, transcriptome changes, protein expression patterns, as well as E-cadherin expression, localization, and gene-level dynamics in mammary epithelial cells undergoing stepwise reversible EMT. ResultsWhile shorter EMT induction induced internalization of E-cadherin protein, surface expression was recovered upon MET without loss of transcript or bulk protein. Conversely, a longer EMT induced stable repression of E-cadherin indicated by loss of chromatin accessibility and induced global expansion of accessible sites across the genome, facilitated by increased engagement of multiple transcription factor families, including AP-1 and SMAD. We observe enrichment for binding sites for the insulator proteins CTCF and BORIS was significantly diminished in both stemness-enriched partial-EMT and partial-MET states and determined that CTCF repression imparts alterations in some histone covalent modifications concomitant with those observed during TGF{beta}-induced EMT. ConclusionsThese findings are indicative of a major role for chromatin looping and reorganization in plasticity, stemness, and partial EMT phenotypes.

cell biology↗

bioRxiv2020

DAISM-DNN: Highly accurate cell type proportion estimation with in silico data augmentation and deep neural networks

Understanding the immune cell abundance of cancer and other disease-related tissues has an important role in guiding disease treatments. Computational cell type proportion estimation methods have been previously developed to derive such information from bulk RNA sequencing (RNA-seq) data. Unfortunately, our results show that the performance of these methods can be seriously plagued by the mismatch between training data and real-world data. To tackle this issue, we propose the DAISM-DNNXMBD1 pipeline that trains a deep neural network (DNN) with dataset-specific training data populated from a small number of calibrated samples using DAISM, a novel Data Augmentation method with an In Silico Mixing strategy. The evaluation results demonstrate that the DAISM-DNN pipeline outperforms other existing methods consistently and substantially for all the cell types under evaluation on real-world datasets.

bioinformatics↗

bioRxiv2020

Transiently structured head domains control intermediate filament assembly

Low complexity (LC) head domains 92 and 108 residues in length are, respectfully, required for assembly of neurofilament light (NFL) and desmin intermediate filaments (IFs). As studied in isolation, these IF head domains interconvert between states of conformational disorder and labile, {beta}-strand-enriched polymers. Solid state nuclear magnetic resonance (ss-NMR) spectroscopic studies of NFL and desmin head domain polymers reveal spectral patterns consistent with structural order. A combination of intein chemistry and segmental isotope labeling allowed preparation of fully assembled NFL and desmin IFs that could also be studied by ss-NMR. Assembled IFs revealed spectra overlapping with those observed for {beta}-strand-enriched polymers formed from the isolated NFL and desmin head domains. Phosphorylation and disease causing mutations reciprocally alter NFL and desmin head domain self-association, yet commonly impede IF assembly. These observations show how facultative structural assembly of LC domains via labile, {beta}-strand-enriched self-interactions may broadly influence cell morphology.

biochemistry↗

bioRxiv2020

Cross-reactive antibody response between SARS-CoV-2 and SARS-CoV infections

The World Health Organization has recently declared the ongoing outbreak of COVID-19, which is caused by a novel coronavirus SARS-CoV-2, as pandemic. There is currently a lack of knowledge in the antibody response elicited from SARS-CoV-2 infection. One major immunological question is concerning the antigenic differences between SARS-CoV-2 and SARS-CoV. We address this question by using plasma from patients infected by SARS-CoV-2 or SARS-CoV, and plasma obtained from infected or immunized mice. Our results show that while cross-reactivity in antibody binding to the spike protein is common, cross-neutralization of the live viruses is rare, indicating the presence of non-neutralizing antibody response to conserved epitopes in the spike. Whether these non-neutralizing antibody responses will lead to antibody-dependent disease enhancement needs to be addressed in the future. Overall, this study not only addresses a fundamental question regarding the antigenicity differences between SARS-CoV-2 and SARS-CoV, but also has important implications in vaccine development.

microbiology↗

bioRxiv2020

Mining Pathway Associations from Networks of Mutual Exclusivity Interactions

Study of pairwise genetic interactions such as mutual exclusivity or synthetic lethality has led to the development of targeted anticancer therapies, and mining the network of such interactions is a common approach used to obtain deeper insights into the mechanism of cancer. A number of useful graph clustering-based tools exist to mine interaction networks. These tools find subgraphs or groups of genes wherein each gene belongs to a single subgraph. However, a gene may be present in multiple groups - for instance, a gene can be involved in multiple signalling pathways. We develop a new network mining algorithm, that does not impose this constraint and can provide a novel pathway-centric view. Our approach is based on finding edge-disjoint bipartite subgraphs of highest weights in an input network of genes, where edge weights indicate the significance of the interaction and each set of nodes in every bipartite subgraph is constrained to belong to a single pathway. This problem is NP-hard and we develop an Integer Linear Program to solve this problem. We evaluate our algorithm on breast and stomach cancer data. Our algorithm mines dense between-pathway interactions that are known to play important roles in cancer and are therapeutically actionable. Our algorithm complements existing network mining tools and can be useful to study the mutational landscape of cancer and inform therapy development.

bioinformatics↗

bioRxiv2020

Integrin β3, a RACK1 interacting protein, is required for porcine reproductive and respiratory syndrome virus infection and NF-κB activation in Marc-145 cells

Porcine reproductive and respiratory syndrome virus (PRRSV) is the pathogen of porcine reproductive and respiratory syndrome (PRRS), which is one of the most economically harmful diseases in modern pig production worldwide. Receptor of activated protein C kinase 1 (RACK1) was previously shown to be indispensable for the PRRSV replication and NF-{kappa}B activation in Marc-145 cells. Here we identified a membrane protein, integrin {beta}3 (ITGB3), as a RACK1-interacting protein. PRRSV infection in Marc-145 cells upregulated the ITGB3 expression. Abrogation of ITGB3 by siRNA knockdown or antibody blocking inhibited PRRSV infection and NF-{kappa}B activation, while on the other hand, overexpression of ITGB3 enhanced PRRSV infection and NF-{kappa}B activation. Furthermore, inhibition of ITGB3 alleviated the cytopathic effects and reduced the TCID50 titer in Marc-145 cells. We also showed that RACK1 and ITGB3 were NF-{kappa}B target genes during PRRSV infection, and that they regulate each other. Our data indicate that ITGB3, presumably as a co-receptor, plays an imperative role for PRRSV infection and NF-{kappa}B activation in Marc-145 cells. PRRSV infection activates a positive feedback loop involving the activation of NF-{kappa}B and upregulation of ITGB3 and RACK1 in Marc-145 cells. The findings would advance our elaborated understanding of the molecular host-pathogen interaction mechanisms underlying PRRSV infection in swine and suggest ITGB3 and NF-{kappa}B signaling pathway as potential therapeutic targets for PRRS control. IMPORTANCEPorcine reproductive and respiratory syndrome virus (PRRSV) is one of the pathogens in pig production worldwide. Several cell surface receptors, such as heparan sulphate, sialoadhesin, vimentin and CD163, were identified to be involved in PRRSV infection in porcine alveolar macrophages (PAMs). We identified a cell surface protein, integrin {beta}3 (ITGB3), as an interacting protein with receptor of activated protein C kinase 1 (RACK1) from Marc-145 cells. ITGB3 interacts with RACK1 and facilitates PRRSV infection and NF-{kappa}B activation in Marc-145 cells, presumably as a co-receptor of CD136 or vimentin. Both ITGB3 and RACK1 were NF-{kappa}B target genes, and they regulate each other. The activation of NF-{kappa}B and the transcription of its downstream genes are beneficial for PRRSV infection/replication. The novel findings would advance our elaborated understanding of the molecular host-pathogen interaction mechanisms underlying PRRSV infection in swine and suggest ITGB3-RACK1-NF-{kappa}B axis as a potential therapeutic target for PRRS control.

microbiology↗

bioRxiv2020

Characterization of a novel NDM-5-harboring plasmid from a carbapenem-resistant Escherichia coli isolate from China

A carbapenem-resistant Escherichia coli (sequence type 5415) strain was isolated from a male patient. S1-PFGE and Southern blotting showed that the blaNDM-5 gene was located on a novel 66-kb IncFII [F2:A-:B-] plasmid. Conjugation assays revealed that the blaNDM-5-bearing plasmid was self-transferrable. Genomic sequencing and comparative analysis suggested that plasmid p2947-NDM5 likely originated from a combination of an IncFII-type backbone and the blaNDM-5 flanking genetic elements. This study highlights the genetic complexity of an NDM-5 carbapenemase and the urgent need for continuous active monitoring. IMPORTANCECarbapenem resistance due to the NDM enzyme has become a serious clinical problem in medical care and public health. We here identified a blaNDM-5-positive E. coli strain ST5414. The blaNDM-5 gene was located on a novel self-transferrable IncFII type plasmid p2947-NDM5. Genomic sequencing and comparative analysis suggested that plasmid p2947-NDM5 likely originated from a combination of an IncFII-type backbone and the blaNDM-5 flanking genetic elements. The genetic context of NDM-5 is highly similar to that of animal origins, and we speculate that the blaNDM-harboring IncFII plasmid has a potential risk of being transmitted from animals to humans and should be paid more attention. Our findings highlight the threat of NDM-5 carbapenemase circulation and the urgency of stringent surveillance and control measures.

genomics↗

bioRxiv2020

Activation of Src-family kinases orchestrate secretion of flaviviruses by targeting mature progeny virions to secretory autophagosomes

Among the various host cellular processes that are hijacked by flaviviruses, very few mechanisms have been described with regard to viral secretion. Here we investigated how flaviviruses exploit the Src family kinases (SFKs) for exit from infected cells. We isolated three members of the SFK family - Src, Fyn and Lyn - that were specifically activated during secretion of Dengue and Zika or their corresponding virus like particles (VLPs). Pharmacological inhibition or genetic depletion of the SFKs blocked virus secretion, most significantly upon Lyn-deficiency. Lyn-/- cells were severely impaired in virus release, and were rescued when reconstituted with wild-type Lyn, but not a kinase- or palmitoylation-deficient Lyn mutant. We further established that Lyn, via its palmitoylation-dependent membrane association, triggered post-Golgi virus transport in specialised Rab11 and Transferrin receptor positive organelles resembling secretory autophagosomes, and distinct from conventional exocytic vesicles. In the absence of Lyn activity or its aberrant membrane association, virions were sorted into the lysosomal pathway for degradation. This mode of export was specifically triggered by processed, and mature, but not by furin-resistant virus particles, and occurred with significantly faster kinetics than the conventional secretory pathway. Our study therefore charts a previously undiscovered Lyn-dependent exit strategy, triggered by flaviviruses in secretory autophagosomes that might enable them to evade circulating antibodies and dictate tissue tropism.

microbiology↗

bioRxiv2020

Individual variability in functional organization of the human and monkey auditory cortex

Accumulating evidence shows that auditory cortex (AC) of humans, and other primates, is involved in more complex cognitive processes than feature segregation only, which are shaped by experience-dependent plasticity and thus likely show substantial individual variability. However, thus far, individual variability of ACs has been considered a methodological impediment rather than a phenomenon of theoretical importance. Here, we examined the variability of ACs using intrinsic functional connectivity patterns in humans and macaques. Our results demonstrate that in humans, functional variability is 1) greater near the non-primary than primary ACs, 2) greater in ACs than comparable visual areas, and 3) greater in the left than right ACs. Remarkably similar modality differences and lateralization of variability were observed in macaques. These connectivity-based findings are consistent with a confirmatory task-based fMRI analysis. The quantitative proof of the exceptional variability of ACs has implications for understanding the evolution of advanced auditory functions in humans.

neuroscience↗

bioRxiv2019

Redox-mediated regulation of a labile, evolutionarily conserved cross-β structure formed by the TDP43 low complexity domain

An evolutionarily conserved low complexity (LC) domain is found within a 152 residue segment localized to the carboxyl-terminal region of the TDP43 RNA-binding protein. This TDP43 LC domain contains ten conserved methionine residues. Self-association of this domain leads to the formation of liquid-like droplets composed of labile, cross-{beta} polymers. Exposure of polymers to low concentrations of H2O2 leads to a phenomenon of droplet melting that can be reversed upon exposure of the oxidized protein to the MsrA and MsrB methionine sulfoxide reductase enzymes, thioredoxin, thioredoxin reductase and NADPH. Morphological features of the cross-{beta} polymers were revealed by a method of H2O2-mediated footprinting. Similar TDP43 LC domain footprints were observed in highly polymerized, hydrogel samples, liquid-like droplet samples, and living cells. The ability of H2O2 to impede cross-{beta} polymerization was abrogated by a prominent ALS-causing mutation that changes methionine residue 337 to valine. These observations offer potentially useful insight into the biological role of TDP43 in facilitating synapse-localized translation, as well as aberrant aggregation of the protein in neurodegenerative disease.

biochemistry↗

bioRxiv2019

Characterization of the novel clinical isolate X-4 containing a new tp0548 sequence-type

BackgroundA novel tp0548 sequence-type was identified in one clinical isolate (X-4) from a patient diagnosed with primary syphilis in Xiamen, China. To precisely define and characterize this new clinical isolate, we performed further genome-scale molecular analysis. Methodology/Principal findingsThe alignment of all published tp0548 genotypes revealed that this new genotype had a unique nucleotide substitution G->T at position 167, and the letter "ao" was assigned to the genotype. Phylogenetic analysis showed that the "ao" genotype belonged to the SS14-like clade of Treponema pallidum (TPA) strains. The genome of the X-4 isolate was then sequenced and analyzed, and the result of a multi-locus sequence analysis using a set of nine chromosomal loci showed that the X-4 isolate was clustered with a monophyletic group of TPA strains, which clearly identified the isolate as a TPA strain. Whole-genome phylogenetic analysis was subsequently conducted to corroborate the TPA strain classification of the X-4 isolate. And the isolate was genetically related to the SS14 strain, with 42 single nucleotide variations and 12 insertions/deletions. In addition, high intrastrain heterogeneity in the length of the poly G/C tracts was found in the TPAChi_0347 locus, which indicated that this gene was most likely involved in phase variation events. The first investigation of the length heterogeneity of the poly A/T tracts showed the variability of the ploy A/T was lower, and all the observed intrastrain variations fell within coding regions. Conclusions/SignificanceThe study demonstrated the X-4 isolate was a TPA isolate containing a novel tp0548 sequence-type. The identification of intrastrain genetic heterogeneity at poly G/C tracts and poly A/T tracts of the isolate could provide a snapshot of the genes that potentially involved in genotype-phenotype variations. These findings provide an unequivocal characterization for better understanding the molecular variation of this emerging isolate. Author summaryThree subspecies of Treponema pallidum (pallidum, pertenue, and endemicum) are increasingly showing overlap in terms of transmission and clinical manifestations. We recently identified a novel tp0548 genotype in the X-4 isolate, which was obtained from an adult male with genital lesions. The novel genotype contained a unique nucleotide substitution G->T at position 167 and belonged to the SS14-like clade of TPA strains, as determined by phylogenetic analysis. We conducted an in-depth exploration of the genome of the X-4 isolate using the pooled segment genome sequencing method followed by Illumina sequencing. Multi-locus sequence analysis of nine chromosomal loci demonstrated that the X-4 isolate was clustered within a monophyletic group of TPA strains, which identified the isolate as a TPA strain. Whole-genome phylogenetic analysis subsequently corroborated the TPA strain classification of the X-4 isolate and revealed that the isolate was very closely related to the SS14 strain, with 42 single nucleotide variations and 12 insertions/deletions. In addition, characterization of the intrastrain heterogeneity in the lengths of homopolymeric tracts in the X-4 isolate showed that the heterogeneity of the poly G/C tracts was greater than that of the poly A/T tracts, and high poly G/C tract diversity was observed in the TPAChi_0347 locus.

genetics↗

bioRxiv2019

Characterization of the Key Region and Phosphorylation Sites of EcaICE1 for its Molecular Interaction with EcaHOS1 Protein from Eucalyptus camaldulensis

ICE1 (inducer of CBF expression 1), a MYC-like bHLH transcriptional activator, plays an important role in plant under cold stress via regulating transcriptional expression of downstream cold-responsive genes. Ubiquitination-proteasome pathway mediated by high expression of osmotically responsive gene1 (HOS1) can effectively induce the degradation of ICE1 and decrease the expression of expression of CBFs and their downstream genes under cold stress response in Arabidopsis, but the knowledge about ubiquitination regulation of ICE1 by HOS1 is still limited in woody plants. In this study, a complete open reading frame of EcaICE1 gene and EcaHOS1 was amplified from the tissue culture seedlings of Eucalyptus camaldulensis. Yeast two-hybrid (Y2H) and BiFC assay results showed that EcaICE1 can interact with EcaHOS1 protein in the nucleus, and further Y2H assay demonstrated that the 126-185 amino acid region at the N-terminus of EcaICE1 protein was indispensable for its interaction with EcaHOS1 protein. Moreover, we found that the amino acids at positions 143, 145, 158 and 184 within the key interaction region were the potential phosphorylation sites of EcaICE1 based on bioinformatics analysis, and that only the substitution of Serine (Ser) 158 by Alanine (Ala) blocked the protein-protein interactions between EcaICE1 and EcaHOS1 by Y2H and {beta}-galactosidase assays using site-direct mutagenesis. In summary, we first reported that EcaICE1 could interact with EcaHOS1 protein in Eucalyptus, and identified Ser 158 of EcaICE1 as the key phosphorylation site for its interaction with EcaHOS1 protein.

plant biology↗

bioRxiv2019

Characterization of transcription activation domain of EcaICE1 and its interaction with EcaSIZ1 in Eucalyptus camaldulensis

SUMOylation in plants is associated with biotic and abiotic stress responses, flowering and other aspects of development, and ICE1 protein SUMOylation by SUMO E3 ligase SIZ1 plays important roles in plant cold tolerance. Here, we reported the subcellular localization of EcaICE1 and its interaction with EcaSIZ1 in Eucalyptus camaldulensis. The genes EcaICE1 and EcaSIZ1 were isolated by homologous cloning. The subcellular localization analysis showed that EcaICE1 was located in nucleus. Bimolecular fluorescence complementation (BiFC) analysis revealed that EcaICE1 could interact with EcaSIZ1 in the nucleus of Nicotiana benthamiana leaves. Moreover, yeast two-hybrid assay confirmed that the amino acid region from position 84 to 126 in EcaICE1 was critical for the strong transactivation activity of EcaICE1 and that the C terminal region from position 361 to 557 in EcaICE1 was the key region for its interaction with EcaSIZ1 by using different truncated lengths of non-transactivation activity of EcaICE1 as the bait protein. Collectively, our results showed that EcaICE1 may have a SUMOylation pathway similar to Arabidopsis thaliana.

plant biology↗

bioRxiv2019

CiteFuse enables multi-modal analysis of CITE-seq data

Multi-modal profiling of single cells represents one of the latest technological advancements in molecular biology. Among various single-cell multi-modal strategies, cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) allows simultaneous quantification of two distinct species: RNA and surface marker proteins (ADT). Here, we introduce CiteFuse, a streamlined package consisting of a suite of tools for pre-processing, modality integration, clustering, differential RNA and ADT expression analysis, ADT evaluation, ligand-receptor interaction analysis, and interactive web-based visualization of CITE-seq data. We show the capacity of CiteFuse to integrate the two data modalities and its relative advantage against data generated from single modality profiling. Furthermore, we illustrate the pre-processing steps in CiteFuse and in particular a novel doublet detection method based on a combined index of cell hashing and transcriptome data. Collectively, we demonstrate the utility and effectiveness of CiteFuse for the integrative analysis of transcriptome and epitope profiles from CITE-seq data.

bioinformatics↗