Biology subjects

Wu, X.

Publications and source records attributed to Wu, X..

At least 289 records · Page 16Linked to original sources

bioRxiv2024

VGLL2 and TEAD1 fusion proteins drive YAP/TAZ-independent transcription and tumorigenesis by engaging p300

Studies on Hippo pathway regulation of tumorigenesis largely center on YAP and TAZ, the transcriptional co-regulators of TEAD. Here, we present an oncogenic mechanism involving VGLL and TEAD fusions that is Hippo pathway-related but YAP/TAZ-independent. We characterize two recurrent fusions, VGLL2-NCOA2 and TEAD1-NCOA2, recently identified in spindle cell rhabdomyosarcoma. We demonstrate that in contrast to VGLL2 and TEAD1, the fusion proteins are strong activators of TEAD-dependent transcription, and their function does not require YAP/TAZ. Furthermore, we identify that VGLL2 and TEAD1 fusions engage specific epigenetic regulation by recruiting histone acetyltransferase p300 to control TEAD-mediated transcriptional and epigenetic landscapes. We showed that small molecule p300 inhibition can suppress fusion proteins-induced oncogenic transformation both in vitro and in vivo. Overall, our study reveals a molecular basis for VGLL involvement in cancer and provides a framework for targeting tumors carrying VGLL, TEAD, or NCOA translocations.

cancer biology↗

bioRxiv2024

FGF2 binds to the allosteric site (site 2) and activates αvβ3 integrin and FGF1 binds to site 2 but suppresses integrin activation by FGF2: a potential mechanism of anti-inflammatory action of FGF1

FGF1 is known as an anti-inflammatory and has suppresses insulin resistance. Its homologue FGF2 is pro-inflammatory. Mechanism of FGF1s anti-inflammatory action and FGF2s pro-inflammatory action are unknown. Several inflammatory cytokines (e.g., CX3CL1, CCL5, and CXCL12, and CD40L) bind to the classical ligand (RGD)-binding site (site 1) of integrin v{beta}3. In addition, they bind to the allosteric site (site 2) of v{beta}3, which is distinct from site 1, and allosterically activate v{beta}3. Site 2 is involved in inflammatory signals since inflammatory lipid mediator 5-hydroxycholesterol binds to site 2 and induces integrin activation and inflammatory signals (e.g., TNF and IL-6 secretion). We thus hypothesized that FGF1 and FGF2 bind to site 2 and affect activation status of integrins. Here we describe that FGF2 bound to site 2 and allosterically activated v{beta}3 integrin. Point mutations in the site 2-binding interface of FGF2 suppressed this activation, indicating that FGF2 binding to site 2 is required for inducing integrin activation. In contrast, FGF1 bound to site 2 but did not activate v{beta}3, and instead suppressed integrin activation induced by FGF2, indicating that FGF1 acts as an antagonist of site 2. These findings suggest that FGF1s anti-inflammatory action is mediated by blocking site 2. FGF1 has potential as an anti-inflammatory agent, but is not appropriate for long-term use since it is potent mitogen. A non-mitogenic FGF1 mutant (R50E), which is defective in binding to site 1 of v{beta}3, suppressed v{beta}3 activation by FGF2 as effectively as WT FGF1. We propose that FGF1 R50E has therapeutic potential for inflammatory diseases.

biochemistry↗

bioRxiv2024

FGF2 binds to the allosteric site (site 2) and activates integrin αIIbβ3 and FGF1 binds to site 2 but suppresses integrin activation by FGF2: A potential mechanism of anti-thrombotic action of FGF1.

It has been believed that platelet integrin IIb{beta}3 recognizes fibrinogen and several ECM proteins, and we recently showed that IIb{beta}3 binds to several inflammatory cytokines (e.g., CCL5, and CXCL12), which are stored in platelet granules. These ligands bind to the classical ligand (RGD)-binding site (site 1) of integrin IIb{beta}3. Also, they bind to the allosteric site (site 2) of IIb{beta}3, which is distinct from site 1, and allosterically activate IIb{beta}3. Site 2 is known to be involved in allosteric integrin activation and inflammatory signaling. FGF2 is also stored in platelet granules and known to be pro-thrombotic, but it is unclear if FGF2 binds to IIb{beta}3. We studied if FGF2 and its homologue FGF1 bind to IIb{beta}3 and induce allosteric activation. FGF1 (not stored in platelet granules) is known to be anti-thrombotic. Mechanism of FGF1s anti-thrombotic action is unknown. Here we describe that FGF1 and FGF2 bound to site 1 of IIb{beta}3, indicating that IIb{beta}3 is a new receptor for FGF1/2. Notably, FGF2 bound to site 2 and allosterically activated IIb{beta}3. Point mutations in the site 2-binding interface of FGF2 suppressed this activation, indicating that FGF2 binding to site 2 is required for activation (FGF2 is an agonist to site 2). In contrast, FGF1 bound to site 2 but did not activate IIb{beta}3, and instead suppressed integrin activation induced by FGF2, indicating that FGF1 acts as an antagonist of site 2. A non-mitogenic FGF1 mutant (R50E), which is defective in binding to site 1 of v{beta}3, suppressed IIb{beta}3 activation by FGF2 as effectively as WT FGF1. We propose that FGF1 R50E has therapeutic potential for anti-thrombosis.

biochemistry↗

bioRxiv2024

Identify compound-protein interaction with knowledge graph embedding of perturbation transcriptomics

The emergence of perturbation transcriptomics provides a new perspective and opportunity for drug discovery, but existing analysis methods suffer from inadequate performance and limited applicability. In this work, we present PertKGE, a method designed to improve compound-protein interaction with knowledge graph embedding of perturbation transcriptomics. PertKGE incorporates diverse regulatory elements and accounts for multi-level regulatory events within biological systems, leading to significant improvements compared to existing baselines in two critical "cold-start" settings: inferring binding targets for new compounds and conducting virtual ligand screening for new targets. We further demonstrate the pivotal role of incorporating multi- level regulatory events in alleviating dataset bias. Notably, it enables the identification of ectonucleotide pyrophosphatase/phosphodiesterase-1 as the target responsible for the unique anti- tumor immunotherapy effect of tankyrase inhibitor K-756, and the discovery of five novel hits targeting the emerging cancer therapeutic target, aldehyde dehydrogenase 1B1, with a remarkable hit rate of 10.2%. These findings highlight the potential of PertKGE to accelerate drug discovery by elucidating mechanisms of action and identifying novel therapeutic compounds.

bioinformatics↗

bioRxiv2024

Discovery of orally bioavailable SARS-CoV-2 papain-like protease inhibitor as a potential treatment for COVID-19

The RNA-dependent RNA polymerase (RdRp), 3C-like protease (3CLpro), and papain-like protease (PLpro) are pivotal components in the viral life cycle of SARS-CoV-2, presenting as promising therapeutic targets. Currently, all FDA-approved antiviral drugs against SARS-CoV-2 are RdRp or 3CLpro inhibitors. However, the mutations causing drug resistance have been observed in RdRp and 3CLpro from SARS-CoV-2, which makes it necessary to develop antivirals with novel mechanisms. Through the application of a structure-based drug design (SBDD) approach, we discovered a series of novel potent non-covalent PLpro inhibitors with remarkable in vitro potency and in vivo PK properties. The co-crystal structures of PLpro with leads revealed that the residues D164 and Q269 around the S2 site are critical for improving the inhibitors potency. The lead compound GZNL-P36 not only inhibited SARS-CoV-2 and its variants at the cellular level with EC50 ranging from 58.2 nM to 306.2 nM, but also inhibited HCoV-NL63 and HCoV-229E with EC50 of 81.6 nM and 2.66 M, respectively. Oral administration of the compound resulted in significantly improved survival and notable reductions in lung viral loads and lesions in SARS- CoV-2 infection mouse model, consistent with RNA-seq data analysis. Our results indicate that PLpro inhibitor is a promising SARS-CoV-2 therapy.

microbiology↗

bioRxiv2024

Caspase-8-mediated CYLD cleavage boots LPS-induced endotoxic shock.

Caspase-8, a pivotal protease intricately involved in various cellular signaling pathways related to cell death and inflammation, has been identified as a contributor to cytokine production during septic shock. However, the mechanisms governing this regulatory role remain enigmatic. In this study, we uncovered that mice harboring a specific mutation in CYLD at its D215 position (CyldD215A/D215A mutant mice), rendering CYLD resistant to caspase8 cleavage, exhibited marked protection against lethal endotoxic shock. Moreover, the removal of Cyld in Caspase8-/-Mlkl-/- mice restored their sensitivity to endotoxic shock, indicating Caspase8 promotes LPS-induced endotoxic shock by cleaving its substrate CYLD and maintaining CYLD stability confers resistance to endotoxic shock. Mechanistically, CYLD was found to catalyze the removal of LUBAC-mediated M1-linked ubiquitination of NF-kB p65 at K301/K303, thereby suppressing the nuclear translocation and activation of p65 for subsequent cytokines production. Notably, the cleaved N-terminal fragment of CYLD (named CP25) is secreted in a TRIF/Caspase8-dependent manner. Moreover, CP25 can be detected in the serum of septic mice, and its levels show a strong correlation with corresponding serum IL-1{beta}, suggesting its potential utility as an inflammatory biomarker. Overall, these findings highlight the significance of CYLD cleavage as a promising therapeutic target and diagnostic marker for endotoxic shock.

immunology↗

bioRxiv2024

Multiplex, multimodal mapping of variant effects in secreted proteins

Despite widespread advances in DNA sequencing, the functional consequences of most genetic variants remain poorly understood. Multiplexed Assays of Variant Effect (MAVEs) can measure the function of variants at scale, and are beginning to address this problem. However, MAVEs cannot readily be applied to the [~]10% of human genes encoding secreted proteins. We developed a flexible, scalable human cell surface display method, Multiplexed Surface Tethering of Extracellular Proteins (MultiSTEP), to measure secreted protein variant effects. We used MultiSTEP to study the consequences of missense variation in coagulation factor IX (FIX), a serine protease where genetic variation can cause hemophilia B. We combined MultiSTEP with a panel of antibodies to detect FIX secretion and post-translational modification, measuring a total of 44,816 effects for 436 synonymous variants and 8,528 of the 8,759 possible missense variants. 49.6% of possible F9 missense variants impacted secretion, post-translational modification, or both. We also identified functional constraints on secretion within the signal peptide and for nearly all variants that caused gain or loss of cysteine. Secretion scores correlated strongly with FIX levels in hemophilia B and revealed that loss of secretion variants are particularly likely to cause severe disease. Integration of the secretion and post-translational modification scores enabled reclassification of 63.1% of F9 variants of uncertain significance in the My Life, Our Future hemophilia genotyping project. Lastly, we showed that MultiSTEP can be applied to a wide variety of secreted proteins. Thus, MultiSTEP is a multiplexed, multimodal, and generalizable method for systematically assessing variant effects in secreted proteins at scale.

genomics↗

bioRxiv2024

Whole-genome resequencing revealed the Origin and Domestication of Chinese Domestic Rabbits

The evolutionary and genetic origins of Chinese indigenous rabbits (Oryctolagus cuniculus) remain largely unclear, despite being among the most recently domesticated animals. We sequenced the whole genomes of 142 individual rabbits and collected 25 resequencing accessions from the NCBI, representing six Chinese indigenous breeds, three other domesticated breeds (serving as a bridge between European wild-type and Chinese domestic populations), and two wild rabbit populations from the Iberian Peninsula and Southern France. Population and demographic analyses suggest that Chinese domestic rabbits are most likely descendants of O. c. cuniculus, native to France 800-1500 years ago. These rabbits likely first arrived in the southeast coastal areas of China through trade before spreading to inland regions. Additionally, there may be other origins for Chinese domestic rabbits. We observed considerable variation in the genetic makeup of maternal ancestry between Chinese domestic rabbits and European wild populations, with Chinese rabbits possessing unique mitochondrial haplotypes. Our analysis also highlights selective sweeps on genes affecting brain and neuronal development, which may have been under strong positive selection during domestication; genes related to starch digestion and fat metabolism, suggesting an evolutionary adaptation to digest high-starch diets; and the white coat phenotype in rabbits, resulting from selection at the melanogenesis-associated transcription factor locus. Overall, our data provide comprehensive insights into the origin and domestication of rabbits and lay the foundation for genome-based breeding.

evolutionary biology↗

bioRxiv2024

N-acetyltransferase 10-mediated mRNA N4-acetylation is Essential for the Translational Regulation During Oocyte Meiotic Maturation in Mice

Mammalian oocyte maturation is driven by the strict translational regulation of maternal mRNAs stored in the cytoplasm. However, the function and mechanism of post-transcriptional chemical modifications, especially the newly identified N4-acetylcytidine (ac4C) modification catalyzed by N-acetyltransferase 10 (NAT10), are unknown. In this study, we developed a low-input ac4C sequencing technology, ac4C LACE-seq, and mapped 8241 ac4C peaks at the whole-transcriptome level using 50 mouse oocytes at the germinal vesicle stage. We profiled the mRNA landscapes of NAT10-interactions and ac4C modifications. The NAT10-interacted and ac4C-modified transcripts are associated with high translation efficiency in oocytes. Oocyte-specific Nat10 knockout wiped out ac4C signals in oocytes and caused severe defects in meiotic maturation and female infertility. ac4C LACE-seq results indicated that Nat10 deletion led to a failure of ac4C deposition on mRNAs encoding key maternal factors, such as MSY2, ZAR1, BTG4, and cyclin B1, which regulate transcriptome stability and maternal-to-zygotic transition. Nat10-deleted oocytes showed decreased mRNA translation efficiency during meiotic maturation, partially due to the direct inhibition of ac4C sites on specific transcripts. In summary, we developed a low-input, high-sensitivity mRNA ac4C profiling approach and highlighted the important physiological function of ac4C in the precise regulation of oocyte meiotic maturation by enhancing translation efficiency.

developmental biology↗

bioRxiv2024

Detection of spatial chromatin accessibility patterns with inter-cellular correlations

Recent advances in spatial sequencing technologies enable simultaneous capture of spatial location and chromatin accessibility of cells within intact tissue slices. Identifying peaks that display spatial variation and cellular heterogeneity is the first and key analytic task for characterizing the spatial chromatin accessibility landscape of complex tissues. Here we propose an efficient and iterative model, Descartes, for spatially variable peaks identification based on the graph of inter-cellular correlations. Through the comprehensive benchmarking for spatially variable peaks identification, we demonstrate the superiority of Descartes in revealing cellular heterogeneity and capturing tissue structure. In terms of computational efficiency, Descartes also outperforms existing methods with spatial assumptions. Utilizing the graph of inter-cellular correlations, Descartes denoises and imputes data via the neighboring relationships, enhancing the precision of downstream analysis. We further demonstrate the ability of Descartes for peak module identification by using peak-peak correlations within the graph. When applied to spatial multi-omics data, Descartes show its potential to detect gene-peak interactions, offering valuable insights into the construction of gene regulatory networks.

bioinformatics↗

bioRxiv2024

Mutational Profiling of SARS-CoV-2 PLpro in human cells reveals requirements for function, structure, and drug escape

SARS-CoV-2, the causative agent of COVID-19, is responsible for the recent global pandemic and remains a major source of mortality. Papain-like protease (PLpro) is a target for SARS-CoV-2 inhibitor development, as it is not only essential for viral replication through cleavage of the viral poly-proteins pp1a and pp1ab, but also has de-ubiquitylation and de-ISGylation activities, which can affect innate immune responses. To understand the features of PLpro that dictate activity and anticipate how emerging PLpro variants will affect function, we employed Deep Mutational Scanning to evaluate the mutational effects on enzymatic activity and protein stability in mammalian cells. We confirm features of the active site and identify all mutations in neighboring residues that support or ablate activity. We characterize residues responsible for substrate binding and demonstrate that although the blocking loop is remarkably tolerant to nearly all mutations, its flexibility is important for enzymatic function. We additionally find a connected network of mutations affecting function but not structure that extends far from the active site. Using our DMS libraries we were able to identify drug-escape variants to a common PLpro inhibitor scaffold and predict that plasticity in both the S4 pocket and blocking loop sequence should be considered during the drug design process.

biochemistry↗

bioRxiv2024

Double-stranded RNA induces retinal pigment epithelium cell degeneration and inflammation

RIG-I signaling has been previously implicated as a driver of inflammation to the retinal pigment epithelium (RPE) during age-related macular degeneration (AMD). Double-stranded RNA (dsRNA) is known to initiate RIG-I signaling and lead to a type I interferon response. We show through shRNA knockdown that RIG-I is essential for initiating an interferon response in iPS-RPE in response to both synthetic dsRNA-mimetic 3p-hpRNA and the double-stranded retrotransposable element Alu. Analysis of human tissue from patients suffering from AMD show accumulation of dsRNA, peaking at the geographic atrophy (GA) stage. Using a new murine model of 3p-hpRNA subretinal challenge to RPE cells, we confirmed that accumulation of dsRNA initiates a type I interferon response, as well as RPE and photoreceptor degeneration. Although RPE response to synthetic dsRNA was acute, extensive leukocyte migration was observed. The results from this study verify the importance of RIG-I signaling in regulating inflammation in the subretinal space and implicates dsRNA accumulation as a driver of AMD pathogenesis.

cell biology↗

bioRxiv2024

DeepPrep: An accelerated, scalable, and robust pipeline for neuroimaging preprocessing empowered by deep learning

Neuroimaging has entered the era of big data. However, the advancement of preprocessing pipelines falls behind the rapid expansion of data volume, causing significant computational challenges. Here, we present DeepPrep, a pipeline empowered by deep learning and workflow manager. Evaluated on over 55,000 scans, DeepPrep demonstrates a 11-fold acceleration, exceptional scalability, and robustness compared to the current state-of-the-art pipeline, providing a promising solution to meet the scalability requirements of neuroimaging.

neuroscience↗

bioRxiv2024

GDOP: A graph convolutional network-based drug "on-target" pathway prediction algorithm

Since most compounds do not induce changes in the transcriptomic levels of their target proteins in vivo, traditional gene set enrichment analysis methods can only retrieve downstream differentially expressed genes, which offer little hints to their targets. To address this problem, we proposed a graph convolutional network-based drug "on-target" pathway prediction algorithm, GDOP, which can predict small pathways that contain target gene through the power of deep learning algorithms. Our model receives as input structural information and biological characteristics (gene expression profiles) of molecules. After being trained on the publicly available LINCS data set, GDOP showed better generalization ability, reaching an AUC-ROC of 0.89 and an averaged Top10 accuracy of 0.63 on the test set. Besides, demonstrated that GDOP was able to use RNA-Seq data as input and achieved accuracy prediction results.

bioinformatics↗

bioRxiv2024

Exploring the repository of de novo designed bifunctional antimicrobial peptides through deep learning

Antimicrobial peptides (AMPs) are attractive candidates to combat antibiotic resistance for their capability to target bio-membranes and restrict a wide range of pathogens. It is a daunting challenge to discover novel AMPs due to their sparse distributions in a vast peptide universe, especially for peptides that demonstrate potencies for both bacterial membranes and viral envelopes. Here we establish a de novo AMP design framework by bridging a deep generative module and a graph-encoding activity regressor. The generative module learns hidden grammars of AMP features and produces candidates sequentially pass antimicrobial predictor and antiviral classifiers. We discover 16 bifunctional AMPs and experimentally validated their abilities to inhibit a spectrum of pathogens in vitro and in animal models. Notably, P076 is a highly potent bactericide with the minimal inhibitory concentration of 0.21 M against multidrug-resistant A. baumannii, while P002 broadly inhibits five enveloped viruses. Our study provides feasible means to uncover sequences that simultaneously encode antimicrobial and antiviral activities, thus bolstering the function spectra of AMPs to combat a wide range of drug-resistant infections.

microbiology↗

bioRxiv2024

Interferons and tuft cell numbers are bottlenecks for persistent murine norovirus infection

Noroviruses (NoVs) are a leading cause of viral gastroenteritis. Despite global clinical relevance, our understanding of how host factors, such as antiviral cytokines interferons (IFNs), modulate NoV population dynamics is limited. Murine NoV (MNoV) is a tractable in vivo model for the study of host regulation of NoV. A persistent strain of MNoV, CR6, establishes a reservoir in intestinal tuft cells for chronic viral shedding in stool. However, the influence of host innate immunity and permissive cell numbers on viral population dynamics is an open question. We generated a pool of 20 different barcoded viruses (CR6BC) by inserting 6-nucleotide barcodes at the 3 position of the NS4 gene and used this pool as our viral inoculum for in vivo infections of different mouse lines. We found that over the course of persistent CR6 infection, shed virus was predominantly colon-derived, and viral barcode richness decreased over time irrespective of host immune status, suggesting that persistent infection involves a series of reinfection events. In mice lacking the IFN-{lambda} receptor, intestinal barcode richness was enhanced, correlating with increased viral intestinal replication. IL-4 treatment, which increases tuft cell numbers, also increased barcode richness, indicating the abundance of permissive tuft cells to be a bottleneck during CR6 infection. In mice lacking type I IFN signaling (Ifnar1-/-) or all IFN signaling (Stat1-/-), barcode diversity at extraintestinal sites was dramatically increased, implicating different IFNs as critical bottlenecks at specific tissue sites. Of interest, extraintestinal barcodes were overlapping but distinct from intestinal barcodes, indicating that disseminated virus represents a distinct viral population than that replicating in the intestine. Barcoded viruses are a valuable tool to explore the influence of host factors on viral diversity in the context of establishment and maintenance of infection as well as dissemination and have provided important insights into how NoV infection proceeds in immunocompetent and immunocompromised hosts.

microbiology↗

bioRxiv2024

Jianpi Jiedu Recipe inhibits proliferation through reactive oxygen species-induced incomplete autophagy and reduces PD-L1 expression in colon cancer

BackgroundJianpi Jiedu Recipe has been used to treat digestive tract tumors in China since ancient times, and its reliability has been proven by clinical research. Currently, the specific biological mechanism of JPJDR in treating tumors is unclear. MethodologyCCK-8 assay was used to detect cell viability. Clone formation assay and EdU assay were used to detect cell proliferation potential. DCFH-DA probe and JC-1 probe were used to detect total intracellular reactive oxygen species and mitochondrial membrane potential, respectively. Western blotting and immunofluorescence were used to detect protein expression level and subcellular localization of cells. RFP-GFP-LC3B reporter system was used to observe the type of autophagy in cells. Xenograft tumor model was used to study the therapeutic effect of JPJDR in vivo. ResultsJPJDR has a good inhibitory effect on various colorectal cancer cells and effectively reduces the proliferation ability of HT29 cells. After treatment with JPJDR, the amount of reactive oxygen species in HT29 cells increased significantly and the mitochondrial membrane potential decreased. JPJDR induced the accumulation of autophagosomes in HT29 cells and was shown to be incomplete autophagy. At the same time, JPJDR reduced the expression of PD-L1.Meanwhile, JPJDR can exert a good therapeutic effect in xenograft tumor mice. ConclusionJPJDR is a low-toxic and effective anti-tumor agent that can effectively treat colon cancer in vitro and in vivo. Its mechanism may be through inducing mitochondrial dysfunction and incomplete autophagy injury to inhibit the proliferation of colon cancer cells.

pharmacology and toxicology↗

bioRxiv2024

Critical Differential Expression Assessment for Individual Bulk RNA-Seq Projects

Finding the right balance of quality and quantity can be important, and it is essential that project quality does not drop below the level where important main conclusions are missed or misstated. We use knock-out and over-expression studies as a simplification to test recovery of a known causal gene in RNA-Seq cell line experiments. When single-end RNA-Seq reads are aligned with STAR and quantified with htseq-count, we found potential value in testing the use of the Generalized Linear Model (GLM) implementation of edgeR with robust dispersion estimation more frequently for either single-variate or multi-variate 2-group comparisons (with the possibility of defining criteria less stringent than |fold-change| > 1.5 and FDR < 0.05). When considering a limited number of patient sample comparisons with larger sample size, there might be some decreased variability between methods (except for DESeq1). However, at the same time, the ranking of the gene identified using immunohistochemistry (for ER/PR/HER2 in breast cancer samples from The Cancer Genome Atlas) showed as possible shift in performance compared to the cell line comparisons, potentially highlighting utility for standard statistical tests and/or limma-based analysis with larger sample sizes. If this continues to be true in additional studies and comparisons, then that could be consistent with the possibility that it may be important to allocate time for potential methods troubleshooting for genomics projects. Analysis of public data presented in this study does not consider all experimental designs, and presentation of downstream analysis is limited. So, any estimate from this simplification would be an underestimation of the true need for some methods testing for every project. Additionally, this set of independent cell line experiments has a limitation in being able to determine the frequency of missing a highly important gene if the problem is rare (such as 10% or lower). For example, if there was an assumption that only one method can be tested for "initial" analysis, then it is not completely clear to the extent that using edgeR-robust might perform better than DESeq2 in the cell line experiments. Importantly, we do not wish to cause undue concern, and we believe that it should often be possible to define a gene expression differential expression workflow that is suitable for some purposes for many samples. Nevertheless, at the same time, we provide a variety of measures that we believe emphasize the need to critically assess every individual project and maximize confidence in published results.

genomics↗