Biology subjects

Wu, B.

Publications and source records attributed to Wu, B..

At least 127 records · Page 7Linked to original sources

bioRxiv2021

Seeing the future: predictive control in neural models of ocular accommodation

Ocular accommodation is the process of adjusting the eyes crystalline lens so as to bring the retinal image into sharp focus. The major stimulus to accommodation is therefore retinal defocus, and in essence, the job of accommodative control is to send a signal to the ciliary muscle which will minimize the magnitude of defocus. In this paper, we first provide a tutorial introduction to control theory to aid vision scientists without this background. We then present a unified model of accommodative control that explains properties of the accommodative response for a wide range of accommodative stimuli. Following previous work, we conclude that most aspects of accommodation are well explained by dual integral control, with a "fast" or "phasic" integrator enabling response to rapid changes in demand, which hands over control to a "slow" or "tonic" integrator which maintains the response to steady demand. Control is complicated by the sensorimotor latencies within the system, which delay both information about defocus and the accommodation changes made in response, and by the sluggish response of the motor plant. These can be overcome by incorporating a Smith predictor, whereby the system predicts the delayed sensory consequences of its own motor actions. For the first time, we show that critically-damped dual integral control with a Smith predictor accounts for adaptation effects as well as for the gain and phase for sinusoidal oscillations in demand. In addition, we propose a novel proportional-control signal to account for the power spectrum of accommodative microfluctuations during steady fixation, which may be important in hunting for optimal focus, and for the nonlinear resonance observed for low-amplitude, high-frequency input. Complete Matlab/Simulink code implementing the model is provided at https://doi.org/10.25405/data.ncl.14945550.

neuroscience↗

bioRxiv2021

Lateral plate mesoderm cell-based organoid system for NK cell regeneration from human pluripotent stem cells

Human pluripotent stem cell (hPSC)-induced NK (iNK) cells are a promising "off-the-shelf" cell product for universal immune therapy. Conventional methods for iNK cell regeneration from hPSCs include embryonic body-formation and feeder-based expansion steps, which bring instability, time-consuming, and high costs for manufacture. In this study, we develop an embryonic body-free, organoid aggregate method for NK cell regeneration from hPSCs. In a short time window of 27-day induction, millions of hPSC input can produce over billions of iNK cells without the necessity of NK cell-expansion feeders. The iNK cells highly express classical toxic granule proteins, apoptosis-inducing ligands, as well as abundant activating and inhibitory receptors. Functionally, the iNK cells eradicate human tumor cells by mechanisms of direct cytotoxity, apoptosis, and antibody-dependent cellular cytotoxicity. This study provides a reliable scale-up method for regenerating human NK cells from hPSCs, which promotes the universal availability of NK cell products for immune therapy.

immunology↗

bioRxiv2021

TIR domains of plant immune receptors are 2',3'-cAMP/cGMP synthetases mediating cell death

2',3'-cAMP is a positional isomer of the well-established second messenger 3',5'-cAMP, but little is known on the biology of this noncanonical cyclic nucleotide monophosphate (cNMP). Toll/interleukin-1 receptor (TIR) domains of nucleotide-binding leucine-rich repeat (NLR) immune receptors have NADase function necessary but insufficient to activate plant immune responses. Here we show that plant TIR proteins, besides being NADases, act as 2',3'-cAMP/cGMP synthetases by hydrolyzing RNA/DNA. Structural data shows that a TIR domain adopts distinct oligomers with dual and exclusive enzymatic activity. Mutations specifically disrupting the synthetase activity abrogate TIR-mediated cell death in Nicotiana benthamiana, supporting an important role for these cNMPs in TIR signaling. Furthermore, the Arabidopsis negative regulator of TIR-NLR signaling, NUDT7 displays 2',3'-cAMP/cGMP but not 3',5'-cAMP/cGMP phosphodiesterase activity and suppresses cell death activity of TIRs in N. benthamiana. Our study identifies a novel family of 2',3'-cAMP/cGMP synthetase and establishes a role for the noncanonical cNMPs in plant immune responses.

plant biology↗

bioRxiv2021

High-quality genome assembly of Cinnamomum burmami (chvar. Borneol) provides insights into the natural borneol biosynthesis

Cinnamomum burmannii (chvar. Borneol) is a well-known medicinal and industrial plant cultivated in the Lingnan region of China. It is the key source from organism of natural borneol (D-borneol), one of the precious and widely used Chinese herbal medicines with a variety of medicinal effects. Here, we report a high-quality chromosome-scale genome assembly of C. burmannii (chvar. Borneol) using Pacbio single-molecule sequencing and Hi-C technology. The assembled genome size was 1.14 GB with a scaffold N50 of 94.30 Mb, while 98.77% of the assembled sequences were anchored on 12 pseudochromosomes including 41549 protein-coding genes. Genomic evolution analysis revealed C. burmannii and C. micranthum shared two Lauraceae unique ancestral whole-genome duplication (WGD) events. Likewise, comparative genomic analysis showed strong collinearity between these two species. Besides, the analysis for Long Terminal Repeat Retrotransposons (LTR-RTs) indicated the outbreak of LTR-RTs insertion made a great contribution to the size difference of genomes between C. burmannii and C. micranthum. Furthermore, the candidate genes in pathway associated with natural borneol synthesis were identified on the genome and their differential expressions were analyzed in various biological tissues. We considered that several of genes in Mevalonate (MVA) Methylerythritol Phosphate (MEP) pathways or in downstream pathway have the potential to be the key factors in the biosynthesis of D-borneol. We also constructed the genome database (CAMD; http://www.cinnamomumdatabase.com/) of Cinnamomum species for a better data utilization in the future. All these results will enrich the genomic data of Lauraceae plants and facilitate genetic improvement of this commercially important plant.

genomics↗

bioRxiv2021

New auranofin analogs with antibacterial properties against Burkholderia clinical isolates

Bacteria of the genus Burkholderia include pathogenic Burkholderia mallei, Burkholderia pseudomallei and the Burkholderia cepacia complex (Bcc). These Gram-negative pathogens have intrinsic drug resistance, which makes treatment of infections difficult. Bcc affects individuals with cystic fibrosis (CF) and the species B. cenocepacia is associated with one of the worst clinical outcomes. Following the repurposing of auranofin as an antibacterial against Gram-positive bacteria, we previously synthetized auranofin analogs with activity against Gram-negatives. In this work, we show that two auranofin analogs, MS-40S and MS-40, have antibiotic activity against Burkholderia clinical isolates. The compounds are bactericidal against B. cenocepacia and kill stationary-phase cells and persisters without selecting for multistep resistance. Caenorhabditis elegans and Galleria mellonella tolerated high concentrations of MS-40S and MS-40, demonstrating that these compounds have low toxicity in these model organisms. In summary, we show that MS-40 and MS-40S have the potential to be effective therapeutic options to treat Burkholderia infections.

microbiology↗

bioRxiv2021

Pandemic, epidemic, endemic: B cell repertoire analysis reveals unique anti-viral responses to SARS-CoV-2, Ebola and Respiratory Syncytial Virus

Immunoglobulin gene heterogeneity reflects the diversity and focus of the humoral immune response towards different infections, enabling inference of B cell development processes. Detailed compositional and lineage analysis of long read IGH repertoire sequencing, combining examples of pandemic, epidemic and endemic viral infections with control and vaccination samples, demonstrates general responses including increased use of IGHV4-39 in both EBOV and COVID-19 infection cohorts. We also show unique characteristics absent in RSV infection or yellow fever vaccine samples: EBOV survivors show unprecedented high levels of class switching events while COVID-19 repertoires from acute disease appear underdeveloped. Despite the high levels of clonal expansion in COVID-19 IgG1 repertoires there is a striking lack of evidence of germinal centre mutation and selection. Given the differences in COVID-19 morbidity and mortality with age, it is also pertinent that we find significant differences in repertoire characteristics between young and old patients. Our data supports the hypothesis that a primary viral challenge can result in a strong but immature humoral response where failures in selection of the repertoire risks off-target effects.

immunology↗

bioRxiv2021

TAS-Seq: a robust and sensitive amplification method for beads-based scRNA-seq

Single-cell RNA-sequencing (scRNA-seq) is valuable for analyzing cellular heterogeneity. Cell composition accuracy is critical for analyzing cell-cell interaction networks from scRNA-seq data. We developed terminator-assisted solid-phase cDNA amplification and sequencing (TAS-Seq) for scRNA-seq based on a terminator, terminal transferase, and nanowell/bead-based scRNA-seq platform; TAS-Seq showed high tolerance to variations in the terminal transferase reaction, which complicate the handling of existing terminal transferase-based scRNA-seq methods. In murine and human lung samples, TAS-Seq yielded scRNA-seq data that were highly correlated with flow-cytometric data, showing higher gene-detection sensitivity and more robust detection of important cell-cell interactions and expression of growth factors/interleukins in cell subsets than 10X Chromium v2 and Smart-seq2. Expanding TAS-Seq application will improve understanding and atlas construction of lung biology at the single-cell level.

genomics↗

bioRxiv2021

A survey of Chinese pig farms and human healthcare isolates reveals separate human and animal MRSA populations

There has been increasing concern that the overuse of antibiotics in livestock farming is contributing to the burden of antimicrobial resistance in people. Farmed animals in Europe and North America, particularly pigs, provide a reservoir for livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA, ST398) found in people. This study was designed to investigate the contribution of MRSA from Chinese pig farms to human infection and carriage.A collection of 603 S. aureus were isolated from 55 pig farms and 4 hospitals (MRSA= 285, 198; MSSA= 50, 70) in central China, a high pig farming density area, during 2017-2018. CC9 MRSA accounting for 93% of all farm MRSA isolates, while no was found in hospitals. ST398 isolates were found on three farms (n = 23) and three hospitals (n = 12). None of the ST398 from this study belong to the livestock clade of the LA-MRSA commonly found in Europe and North America. The hospital ST398 MRSA isolates formed a clade that was clearly separate from the farm ST398 MRSA and MSSA isolates, and all possessed human immune evasion cluster genes which were absent from all the pig farm ST398 isolates. Despite the presence of high levels of MRSA found on Chinese pig farms we found no evidence of them spilling over to the human population. Nevertheless, the ST398 MRSA obtained from human samples appear to be part of a widely distributed lineage in China. And the new animal adapted ST398 lineage that emerged in China should also be alarmed. ImportanceWe disclosed the fact that although the high MRSA positive rate in Chinese hospitals and pig farms should be alarmed, they might be two separate issues. The new CC398 clades we identified highlight that the host adaption of the MRSA lineage is kept changing. These results suggest that continued surveillance of MRSA in livestock is necessary. We found that the pig farm MRSA isolates had unique antimicrobial resistance genes while most of the hospital MRSA isolates had human immune evasion cluster genes. These features could be used to distinguish the pig farm associated S. aureus in clinical laboratories. The policies of reducing antimicrobials use in livestock were implemented in China since 2020. Our study described the situation of MRSA populations in pig farms and hospitals in Central China before 2020, which provides a potential opportunity for future studies to evaluate the effects of the policies.

microbiology↗

bioRxiv2021

Structural basis for the therapeutic advantage of dual and triple agonists at the human GIP, GLP-1 or GCG receptors

Glucose homeostasis, regulated by glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1) and glucagon (GCG) is critical to human health. Several multi-targeting agonists at GIPR, GLP-1R or GCGR, developed to maximize metabolic benefits with reduced side-effects, are in clinical trials to treat type 2 diabetes and obesity. To elucidate the molecular mechanisms by which tirzepatide, a GIPR/GLP-1R dualagonist, and peptide 20, a GIPR/GLP-1R/GCGR triagonist, manifest their superior efficacies over monoagonist such as semaglutide, we determined cryo-electron microscopy structures of tirzepatide-bound GIPR and GLP-1R as well as peptide 20-bound GIPR, GLP-1R and GCGR The structures reveal both common and unique features for the dual and triple agonism by illustrating key interactions of clinical relevance at the atomic level. Retention of glucagon function is required to achieve such an advantage over GLP-1 monotherapy. Our findings provide valuable insights into the structural basis of functional versatility and therapeutic supremacy of tirzepatide and peptide 20.

molecular biology↗

bioRxiv2021

Regeneration of humoral immunity from pluripotent stem cells by defined transcription factors

Regeneration of humoral immunity from pluripotent stem cells (PSCs) is a crucial aim in translational medicine. However, reconstitution of complete, sustained, and functional B lymphopoiesis from PSCs has not yet been developed. Here, we successfully achieved regenerative B lymphopoiesis in B-cell deficient animals transplanted with PSC-derived hematopoietic progenitors (iHPCs) guided by synergistic expression of Runx1, Hoxa9, and Lhx2. Upon transplantation, the iHPCs immediately gave rise to pro/pre-B cells in recipients bone marrow, which were able to further differentiate into the entire B cell lineages, including innate B-1a, B-1b, MZ B cells, as well as adaptive FO B cells. In responding to antigen stimuli, the regenerative B cells produced adaptive humoral immune responses, sustained a prolonged antigen-specific antibody production, and formed immune-memory. Particularly, the regenerative B cells in spleen showed developing patterns of immunoglobulin chain-switch and hyper-mutation via a cross-talk with the host T follicular helper cells, which eventually formed T cell-dependent humoral responses. This study provides de novo evidence that B lymphopoiesis can be regenerated from PSCs via a HSC-independent approach, which provides insights into treating B-cell related humoral deficiencies using PSCs as unlimited cell resource.

immunology↗

bioRxiv2021

Structures of the human cholecystokinin receptors in complex with agonists and antagonists

Cholecystokinin receptors, CCKAR and CCKBR, are important neuro-intestinal peptide hormone receptors and play a vital role in food intake and appetite regulation. Here we report three crystal structures of the human CCKAR in complex with different ligands, including one peptide agonist and two small-molecule antagonists, as well as two cryo-electron microscopy structures of CCKBR-gastrin in complex with Gi2 and Gq, respectively. These structures reveal the recognition pattern of different ligand types and the molecular basis of peptide selectivity in the cholecystokinin receptor family. By comparing receptor structures in different conformational states, a stepwise activation process of cholecystokinin receptors is proposed. Combined with pharmacological data, our results provide atomic details for differential ligand recognition and receptor activation mechanisms. These insights will facilitate the discovery of potential therapeutics targeting cholecystokinin receptors.

biophysics↗

bioRxiv2021

Structural basis for ligand recognition and G protein-coupling promiscuity of the cholecystokinin A receptor

Cholecystokinin A receptor (CCKAR) belongs to family A G protein-coupled receptors (GPCRs) and regulates nutrient homeostasis upon stimulation by cholecystokinin (CCK). It is an attractive drug target for gastrointestinal and metabolic diseases. One distinguishing feature of CCKAR is its ability to interact with sulfated ligand and to couple with divergent G protein subtypes, including Gs, Gi, and Gq. However, the basis for G protein coupling promiscuity and ligand recognition by CCKAR remain unknown. Here we present three cryo-electron microscopy (cryo-EM) structures of sulfated CCK-8 activated CCKAR in complex with Gs, Gi, and Gq heterotrimers, respectively. In these three structures, CCKAR presents a similar conformation, whereas conformational differences in "wavy hook" of G subunits and ICL3 of the receptor serve as determinants in G protein coupling selectivity. These structures together with mutagenesis data provide the framework for understanding the G protein coupling promiscuity by CCKAR and uncover the mechanism of receptor recognition by sulfated CCK-8.

biophysics↗

bioRxiv2021

A temperate Siphoviridae bacteriophage isolate from Siberian tiger enhances the virulence of Methicillin-resistant Staphylococcus aureus through distinct mechanisms

The emergence and worldwide spread of Methicillin-resistant Staphylococcus aureus (MRSA) poses a threat to human health. While bacteriophages are recognized as an effective alternative to treat infections caused by drug resistant pathogens, some bacteriophages in particular the temperate bacteriophage may also influence the virulence of the host bacteria in distinct ways. In this study, we isolated a bacteriophage vB_Saus_PHB21 from an epidermal sample of Siberian tiger (Panthera tigris altaica) using a MRSA strain SA14 as the indicator. Our following laboratory tests and whole genome sequencing analyses revealed that vB_Saus_PHB21 was a temperate bacteriophage belonging to the Siphoviridae family, and this bacteriophage did not contain any virulence genes. However, the integration of PHB21 genome into the host MRSA increased the bacterial capacities of cell adhesion, cell invasion, anti-phagocytosis and biofilm formation. Challenge of the lysogenic strain (SA14+) caused severer mortalities in both Galleria mellonella and mouse models. Mice challenged with SA14+ showed more serious organ lesions and produced higher inflammatory cytokines (IL-8, IFN-{gamma} and TNF-) compared to those challenged with SA14. In mechanism, we found the integration of PHB21 genome caused the upregulated expression of many genes encoding products involved in bacterial biofilm formation, adherence and invasion to host cells, anti-phagocytosis, and virulence. This study may provide novel knowledge of "bacteria-phage-interactions" in MRSA. IMPORTANCEThe interaction between bacteriophage and bacteria is like a "double-edged sword": phages can either kill bacteria, or they may contribute to the bacterial fitness and virulence. In general, phages have positive impacts on bacterial fitness and virulence mainly because they carry antimicrobial resistance genes (ARGs) and/or virulence factors encoding genes (VFGs) and they can spread these harmful genes to the host bacteria. However, we found those phages which do not harbor ARGs and/or VFGs may also enhance the bacterial fitness and virulence. In addition, we also found the integration of phage genomes may lead to the upregulated expression of virulence associated genes in bacteria. Our study may provide new insights to redefine the relationship between phage and bacteria, and the results may also remind a cautious way to set phage-therapy for bacterial infections, before which the safety of a phage intends to be used should be fully evaluated.

microbiology↗

bioRxiv2021

Capacity to erase gene occlusion is a defining feature distinguishing naive from primed pluripotency

Pluripotent stem cells can exist in either the naive state representing a developmental blank slate or the downstream primed state poised for differentiation. Currently, known differences between these two states are mostly phenomenological, and none can adequately explain why the two states should differ in developmental priming. Gene occlusion is a mode of epigenetic inactivation that renders genes unresponsive to their cognate transcriptional activators. It plays a crucial role in lineage restriction. Here, we report that a defining feature distinguishing the two pluripotent states lies in the ability of naive but not primed cells to erase occlusion. This "deocclusion" capacity requires Esrrb, a gene expressed only in the naive but not primed state. Notably, Esrrb silencing in the primed state is itself due to occlusion. Collectively, our data argue that the Esrrb-dependent deocclusion capacity in naive cells is key for sustaining naive pluripotency, and the loss of this capacity in the primed state via the occlusion of Esrrb poises cells for differentiation.

molecular biology↗

bioRxiv2021

ORAI1 establishes resistance to SARS-CoV-2 infection by regulating tonic type I interferon signaling

ORAI1 and STIM1 are the critical mediators of store-operated Ca2+ entry by acting as the pore subunit and an endoplasmic reticulum-resident signaling molecule, respectively. In addition to Ca2+ signaling, STIM1 is also involved in regulation of a cytosolic nucleic acid sensing pathway. Using ORAI1 and STIM1 knockout cells, we examined their contribution to the host response to SARS-CoV-2 infection. STIM1 knockout cells showed strong resistance to SARS-CoV-2 infection due to enhanced type I interferon response. On the contrary, ORAI1 knockout cells showed high susceptibility to SARS-CoV-2 infection as judged by increased expression of viral proteins and a high viral load. Mechanistically, ORAI1 knockout cells showed reduced homeostatic cytoplasmic Ca2+ concentration and severe impairment in tonic interferon signaling. Transcriptome analysis showed downregulation of multiple cellular defense mechanisms, including antiviral signaling pathways in ORAI1 knockout cells, which are likely due to reduced expression of the Ca2+-dependent transcription factors of the activator protein 1 (AP-1) family and MEF2C. Our results identify a novel role of ORAI1-mediated Ca2+ signaling in regulating the baseline type I interferon level, which is a determinant of host resistance to SARS-CoV-2 infection.

microbiology↗

bioRxiv2021

A Synthetic, Closed-Looped Gene Circuit for the Autonomous Regulation of RUNX2 Activity during Chondrogenesis

The transcription factor RUNX2 is a key regulator of chondrocyte phenotype during development, making it an ideal target for prevention of undesirable chondrocyte maturation in cartilage tissue engineering strategies. Here, we engineered an autoregulatory gene circuit (cisCXp-shRunx2) that negatively controls RUNX2 activity in chondrogenic cells via RNA interference initiated by a tunable synthetic Col10a1-like promoter (cisCXp). The cisCXp-shRunx2 gene circuit is designed based on the observation that induced RUNX2 silencing after early chondrogenesis enhances the accumulation of cartilaginous matrix in ATDC5 cells. We show that the cisCXp-shRunx2 initiates RNAi of RUNX2 in maturing chondrocytes in response to the increasing intracellular RUNX2 activity without interfering with early chondrogenesis. The induced loss of RUNX2 activity in turn negatively regulates the gene circuit itself. Moreover, the efficacy of RUNX2 suppression from cisCXp-shRunx2 can be controlled by modifying the sensitivity of cisCXp promoter. Finally, we show the efficacy of inhibiting RUNX2 in preventing matrix loss in human MSC-derived cartilage under conditions that induce chondrocyte hypertrophic differentiation, including inflammation. Overall, our results demonstrated that the negative modulation of RUNX2 activity with our autoregulatory gene circuit enhanced matrix synthesis and resists ECM degradation by reprogrammed MSC-derived chondrocytes in response to the microenvironment of the degenerative joint.

genetics↗

bioRxiv2021

Population genomics of Salmonella enterica serovar Weltevreden ST365, an emerging predominant causative agent of diarrheal disease

Salmonella enterica serovar Weltevreden is a recently emerged pathogen, and as such we lack a comprehensive knowledge of its microbiology, genomics, epidemiology and biogeography. In this study, we analyzed 174 novel S. Weltevreden isolates including 111 isolates recovered from diarrheal patients in China between 2006 and 2017. Our results demonstrate that the ST365 clone was the predominant causative agent of the diarrhea-outbreak during this period, as vast majority of the isolates recovered from diarrheal patients belonged to this sequence type (97.37%, 74/76). We also determined the ST365 clone as the predominant sequence type of S. Weltevreden from diarrheal patients globally from previously published sequences (97.51%, 196/201). In order to determine the possible antimicrobial genes and virulence factors associated with S. Weltevreden, we performed whole genome sequencing on our novel isolates. We were able to identify a range of key virulence factors associated with S. Weltevreden that are likely to be beneficial to their fitness and pathogenesis. Furthermore, we were able to isolate a novel 100.03-kb IncFII(S) type virulence plasmid that used the same replicon as pSPCV virulence plasmid. Importantly, we demonstrated through plasmid elimination a functional role for this plasmid in bacterial virulence. These findings are critical to further our knowledge of this high consequence pathogen. ImportanceSalmonella Weltevreden is a newly emerged foodborne pathogen and has caused several outbreaks of diarrheal diseases in some regions in the world. However, comprehensive knowledge of microbiology, genomics, epidemiology and biogeography of this newly emerged pathogen is still lack. In this study, we made an unexpected discovery that S. Weltevreden sequence type (ST) 365 is the causative agent in the diarrhea-outbreak in China and many other regions of the world. We also shown that this sequence type was widely recovered from animal, food, and environmental samples collected in different regions in the world. Importantly, we discovered a novel IncFII(S) type virulence plasmid commonly carried by S. Weltevreden strains of both human, animal, and food origins. These data facilitate future studies investigating the emergence of S. Weltevreden involved in diarrheal outbreaks and the global spread of S. Weltevreden strains.

microbiology↗

bioRxiv2021

Subgroup-specific gene expression profiles and mixed epistasis in chronic lymphocytic leukemia

Despite the extensive catalogue of recurrent mutations in chronic lymphocytic leukaemia (CLL), the diverse molecular driving events and the resulting range of disease phenotypes remain incompletely understood. To study the molecular heterogeneity of CLL, we performed RNA-sequencing on 184 CLL patient samples. Unsupervised analysis revealed two major independent axes of gene expression variation: the first one aligned with the mutational status of the immunoglobulin heavy variable (IGHV) genes, and concomitantly, with the three-group stratification of CLL by global DNA methylation pattern, and affected biological functions including B- and T-cell receptor signaling. The second one aligned with trisomy 12 status and affected chemokine signaling. Furthermore, we searched for differentially expressed genes associated with gene mutations and copy-number aberrations and detected strong signatures for TP53, BRAF and SF3B1, as well as for del(11)(q22.3), del(17)(p13) and del(13)(q14) beyond the dosage effect. We discovered strong non-additive effects (i.e., genetic interactions, or epistasis) of IGHV mutation status and trisomy 12 on multiple phenotypes, including the expression of 893 genes. Multiple types of epistasis were observed, including synergy, buffering, suppression and inversion. Our study reveals previously underappreciated gene expression signatures for (epi)genomic variants in CLL and the presence of epistasis between them. The findings will serve as a reference for a functional resolution of CLL molecular heterogeneity.

genomics↗