Biology subjects

Peng, F.

Publications and source records attributed to Peng, F..

At least 37 records · Page 2Linked to original sources

bioRxiv2023

Deletion of SMC renders FtsK essential in Corynebacterium glutamicum

Structural maintenance of chromosomes (SMC) are ubiquitously distributed proteins involved in chromosome organization. Deletion of smc causes severe growth phenotypes in many organisms. Surprisingly, smc can be deleted in Corynebacterium glutamicum, a member of the Actinomycetota phylum, without any apparent growth phenotype. Earlier work has shown that SMC in C. glutamicum is loaded in a ParB-dependent fashion to the chromosome and functions in replichore cohesion. The unexpected absence of a growth phenotype in the smc mutant prompted us to screen for unknown synthetic interactions within C. glutamicum. Therefore, we generated a high-density Tn-5 library based on wild-type and smc-deleted C. glutamicum strains. The transposon sequencing (Tn-seq) data revealed that the DNA-translocase FtsK is essential in a smc deletion strain. FtsK localized to the septa and cell poles in wild type cells, however deletion of smc resulted in a decreased polar FtsK localization. Single-particle tracking analysis further suggests that prolonged FtsK complex activity is both required and sufficient to make up for the absence of SMC, thus achieving efficient chromosome segregation in C. glutamicum. Further, single molecule dynamics of FtsK is influenced, albeit indirectly, by DNA-loaded SMC. Deletion of ParB results in an increased of both SMC and FtsK mobility. While the first change agrees with previous data that show how ParB is essential for SMC loading on DNA, the latter suggests that FtsK mobility is affected in cells with defects in chromosome organization. Based on our data we propose a simple, yet efficient mechanism for efficient DNA segregation in C. glutamicum, even in absence of SMC proteins. ImportanceFaithful DNA segregation is of fundamental importance for life. Bacteria have efficient systems to coordinate chromosome compaction, DNA segregation and cell division. A key factor in DNA compaction is the SMC-complex that is found to be essential in many bacteria. In members of the Actinomycetota smc is dispensable, but the reason for this was unclear. We show here that the divisome associated DNA-pump FtsK can compensate SMC loss and the subsequent loss in correct chromosome organization. In cells with distorted chromosomes, FtsK functions for an extended period of time at the septum, until chromosomes are segregated.

microbiology↗

bioRxiv2023

Hybrid Mimulus flowers attract a new pollinator

Hybridization is common in flowering plants and is believed to be an important force driving adaptation and speciation. The hybrid flowers often have new trait combinations, which, theoretically, could attract new pollinators. In this study, we found that the hybrids between a hummingbird-pollinated species Mimulus cardinalis and a self-pollinated species Mimulus parishii attract bumblebees (Bombus impatiens), a pollinator not attracted to either of the progenitor species. This novel attraction is explained by several floral traits in hybrids, including petal color, nectar concentration, and corolla size. We also found that the YUP locus, previously shown to be important in bee attraction in other Mimulus species, also played an important role in this novel attraction. Hybrid plants attraction to new pollinators could be an underexplored avenue for pollinator shift and speciation.

ecology↗

bioRxiv2023

Evolutionary fingerprints of EMT in pancreatic cancers

Mesenchymal plasticity has been extensively described in advanced and metastatic epithelial cancers; however, its functional role in malignant progression, metastatic dissemination and therapy response is controversial. More importantly, the role of epithelial mesenchymal transition (EMT) and cell plasticity in tumor heterogeneity, clonal selection and clonal evolution is poorly understood. Functionally, our work clarifies the contribution of EMT to malignant progression and metastasis in pancreatic cancer. We leveraged ad hoc somatic mosaic genome engineering, lineage tracing and ablation technologies and dynamic genetic reporters to trace and ablate tumor-specific lineages along the phenotypic spectrum of epithelial to mesenchymal plasticity. The experimental evidences clarify the essential contribution of mesenchymal lineages to pancreatic cancer evolution and metastatic dissemination. Spatial genomic analysis combined with single cell transcriptomic and epigenomic profiling of epithelial and mesenchymal lineages reveals that EMT promotes with the emergence of chromosomal instability (CIN). Specifically tumor lineages with mesenchymal features display highly conserved patterns of genomic evolution including complex structural genomic rearrangements and chromotriptic events. Genetic ablation of mesenchymal lineages robustly abolished these mutational processes and evolutionary patterns, as confirmed by cross species analysis of pancreatic and other human epithelial cancers. Mechanistically, we discovered that malignant cells with mesenchymal features display increased chromatin accessibility, particularly in the pericentromeric and centromeric regions, which in turn results in delayed mitosis and catastrophic cell division. Therefore, EMT favors the emergence of high-fitness tumor cells, strongly supporting the concept of a cell-state, lineage-restricted patterns of evolution, where cancer cell sub-clonal speciation is propagated to progenies only through restricted functional compartments. Restraining those evolutionary routes through genetic ablation of clones capable of mesenchymal plasticity and extinction of the derived lineages completely abrogates the malignant potential of one of the most aggressive form of human cancer.

cancer biology↗

bioRxiv2023

The Arabidopsis BUB1/MAD3 family protein BMF3 requires BUB3.3 to recruit CDC20 to kinetochores in spindle assembly checkpoint signaling

Mitosis is monitored by the spindle assembly checkpoint (SAC) which remains active until all chromosomes have their kinetochores attached to microtubules originated from opposite spindle poles. Plants produce both highly conserved and sequence-diverged SAC components, so it has been largely unknown how SAC activation leads to the assembly of these proteins at the unattached kinetochores to prevent anaphase onset in plants. In Arabidopsis thaliana, the noncanonical BUB3.3 protein was detected at kinetochores throughout mitosis, unlike MAD1 and the plant specific BUB1/MAD3 family protein BMF3 that associated with unattached chromosomes only. However, BUB3.3 was required to arrest mitotic progression when one or more chromosomes did not congress at the metaphase plate. Nevertheless, BUB3.3 was not required for the kinetochore localization of other SAC components and vice versa. BUB3.3 specifically interacted with BMF3 in a novel region containing two internal repeats that were not required for the kinetochore localization of BMF3. This interaction was important for BMF3 to recruit the CDC20 protein to the unattached kinetochores. Our results showed that the Arabidopsis BUB3.3 protein functioned in the activation of BMF3 for CDC20 recruitment, rather than the recruitment of BMF proteins as what has been found in fungi and animals, in order to arrest mitosis at prometaphase. Therefore, activated SAC resulted in BUB3.3-independent localization of BMF3 and MAD1 to kinetochores and BUB3.3-dependent licensing of BMF3 for CDC20 recruitment in A. thaliana. SIGNIFICANCE STATEMENTMitotic progression into anaphase is monitored by spindle assembly checkpoint that is poorly understood in plants. Using Arabidopsis thaliana as a reference system, we discovered a novel interaction pattern centered at the BUB1 and MAD3 protein BMF3 at kinetochores. A noncanonical isoform of the evolutionarily conserved BUB3 family protein BUB3.3 interacted with two novel internal repeats in BMF3 for recruiting the CDC20 protein to unattached kinetochores in order to inhibit its function in anaphase onset. Hence, our work sheds light on how spindle assembly checkpoint operates in flowering plants that produce the highly conserved BUB3.3 protein but highly divergent BMF proteins.

plant biology↗

bioRxiv2023

Dissociable roles of the auditory midbrain and cortex in processing the statistical features of natural sound textures

It is well established that sound texture perception takes advantage of a hierarchy of time-averaged statistical features of acoustic stimuli, but much remains unclear about how these statistical features are processed in auditory subcortical and cortical regions. Here, we compared the neural representation of sound textures in the inferior colliculus (IC), and primary and non-primary auditory cortex (AC) of anesthetized rats with texture morph stimuli which gradually add statistical features of increasingly higher order. We generated texture morphs for a representative subset of 13 sound textures, chosen to span the three principal component dimensions of a corpus of 200 natural texture recordings. For each of the 13 texture types, six different exemplar morphs were synthesized using different random seeds. All exemplars of each texture type have the same long term statistics, but they differ in their acoustic waveforms. Meanwhile, different texture types differ in statistical features as well as waveforms. An analysis of transient and ongoing multi-unit responses to our stimulus set showed that the IC units were sensitive to every type of statistical feature, albeit to a varying extent, but only a small proportion of AC units were overtly sensitive to any statistical features. Differences in texture types explained more of the variance of IC neural responses than did differences in exemplars, indicating a degree of "texture-type tuning" in the IC, but this was, perhaps surprisingly, not the case for AC responses. We also evaluated the accuracy of texture type classification from single-trial population activity and found that IC responses became more informative as more summary statistics were included in the texture morphs, while for AC population responses classification performance remained constant, and consistently lower, than for the IC. These results argue against the idea that AC plays an important role in encoding statistical features of natural sound textures.

physiology↗

bioRxiv2022

A novel nuclease is the executing part of a bacterial plasmid defense system

Cells are continuously facing the risk of taking up foreign DNA that can compromise genomic and cellular integrity. Therefore, bacteria are in a constant arms race with mobile genetic elements such as phages, transposons and plasmids. They have developed several active strategies against invading DNA molecules that can be seen as a bacterial innate immune system. Anti-phage systems are usually organized in defense islands and can consist of restriction-modification (R-M) systems, CRISPR-Cas, and abortive infection (Abi) systems. Despite recent advances in the field, much less is known about plasmid defense systems. We have recently identified the MksBEFG system in Corynebacterium glutamicum as a novel plasmid defense system which comprises homologues of the condensin system MukFEB. Here, we investigated the molecular arrangement of the MksBEFG complex. Importantly, we identified MksG as a novel nuclease that degrades plasmid DNA and is, thus, the executing part of the system. The crystal structure of MksG revealed a dimeric assembly through its DUF2220 C-terminal domains. This domain is homologous to the TOPRIM domain of the topoisomerase II family of enzymes and contains the corresponding divalent ion binding site that is essential for DNA cleavage in topoisomerases, explaining the in vitro nuclease activity of MksG. We further show that the MksBEF subunits exhibit an ATPase cycle similar to MukBEF in vitro and we reason that this reaction cycle, in combination with the nuclease activity provided by MksG, allows for processive degradation of invading plasmids. Super-resolution localization microscopy revealed that the Mks system is spatially regulated via to the polar scaffold protein DivIVA. Introduction of plasmids increases the diffusion rate and alters the localization of MksG, indicating an activation of the system in vivo.

microbiology↗

bioRxiv2022

"What" and "When" Predictions Modulate Auditory Processing in a Contextually Specific Manner

Extracting regularities from ongoing stimulus streams to form predictions is crucial for adaptive behavior. Such regularities exist in terms of the content of the stimuli (i.e., "what" it is) and their timing (i.e., "when" it will occur), both of which are known to interactively modulate sensory processing. In real-world stimulus streams, regularities also occur contextually - e.g. predictions of individual notes vs. melodic contour in music. However, it is unknown whether the brain integrates predictions in a contextually congruent manner (e.g., if slower "when" predictions selectively interact with complex "what" predictions), and whether integrating predictions of simple vs. complex features rely on dissociable neural correlates. To address these questions, our study employed "what" and "when" violations at different levels - single tones (elements) vs. tone pairs (chunks) - within the same stimulus stream, while neural activity was recorded using electroencephalogram (EEG) in participants (N=20) performing a repetition detection task. Our results reveal that "what" and "when" predictions interactively modulated stimulus-evoked response amplitude in a contextually congruent manner, but that these modulations were shared between contexts in terms of the spatiotemporal distribution of EEG signals. Effective connectivity analysis using dynamic causal modeling showed that the integration of "what" and "when" prediction selectively increased connectivity at relatively late cortical processing stages, between the superior temporal gyrus and the fronto-parietal network. Taken together, these results suggest that the brain integrates different predictions with a high degree of contextual specificity, but in a shared and distributed cortical network. Significance statementPredictions of stimulus features, present in different statistically-regular contexts in the environment, are crucial to forming adaptive behavior. However, it is unknown if the brain integrates predictions selectively according to such contextual differences. By recording human electroencephalography during experimental manipulations of time-based and content-based predictions, we found that those predictions interactively modulated neural activity in a contextually congruent manner, such that local (vs. global) time-based predictions modulated content-based predictions of sequence elements (vs. chunks). These modulations were shared between contextual levels in terms of the spatiotemporal distribution of neural activity. This suggests that the brain integrates different predictions with a high degree of contextual specificity, but in a shared and distributed cortical network.

neuroscience↗

bioRxiv2022

Wilcoxon rank-sum test still outperforms dearseq after accounting for the normalization impact in semi-synthetic RNA-seq data simulation

In this response to the correspondence by Hejblum et al. [1], we clarify the reasons why we ran the Wilcoxon rank-sum test on the semi-synthetic RNA-seq samples without normalization, and why we could only run dearseq with its built-in normalization, in our published study [2]. We also argue that no normalization should be performed on the semi-synthetic samples. Hence, for a fairer method comparison and using the updated dearseq package by Hejblum et al., we re-run the six differential expression methods (DESeq2, edgeR, limma-voom, dearseq, NOISeq, and the Wilcoxon rank-sum test) without normalizing the semi-synthetic samples, i.e., under the "No normalization" scheme in [1]. Our updated results show that the Wilcoxon rank-sum test is still the best method in terms of false discovery rate (FDR) control and power performance under all settings investigated.

bioinformatics↗

bioRxiv2022

Bumblebees retrieve only the ordinal ranking of foraging options when comparing memories obtained in distinct settings

Are animals preferences determined by absolute memories for options (e.g., reward sizes) or by their remembered ranking (better/worse)? The only studies examining this question suggest humans and starlings utilize memories for both absolute and relative information. We show that bumblebees make decisions using only memories of ordinal comparisons. After learning to discriminate pairs of different flowers by sucrose concentration, bumblebees preferred flowers (in novel pairings) with 1) higher ranking over equal absolute reward, 2) higher ranking over higher absolute reward, and 3) identical qualitative ranking but different quantitative ranking equally. Despite these suboptimal choices, bumblebees found the optimal option in an ecologically relevant foraging task. Our results illuminate a divergent mechanism of learned preferences that may have arisen from adaptations to bumblebees natural environment.

animal behavior and cognition↗

bioRxiv2022

IRONMAN interacts with OsHRZ1 and OsHRZ2 to maintain Fe homeostasis

IRONMAN is a family of small peptides which positively regulate the Fe deficiency response. However, the molecular mechanism by which OsIMA1 and OsIMA2 regulate Fe homeostasis was unclear. Here, we reveal that OsIMA1 and OsIMA2 interact with the potential Fe sensors, OsHRZ1 and OsHRZ2. OsIMA1 and OsIMA2 contain a conserved 17-amino acid C-terminal region which is responsible for the interactions with OsHRZ1 and OsHRZ2. The OsIMA1 overexpressing plants have the increased seed Fe concentration and the reduced fertility, as observed in the hrz1-2 loss-of-function mutant plants. Moreover, the expression trends of Fe deficiency inducible genes in the OsIMA1 overexpressing plants are the same to those in the hrz1-2. Co-expression assays suggest that OsHRZ1 and OsHRZ2 promote the degradation of OsIMA1 proteins. As the interaction partners of OsHRZ1, the OsPRI proteins also interact with OsHRZ2. The conserved C-terminal region of four OsPRIs contributes to the interactions with OsHRZ1 and OsHRZ2. An artificial IMA (aIMA) derived from the C-terminal of OsPRI1 can be also degraded by OsHRZ1. Moreover, the aIMA overexpressing rice plants accumulate more Fe without reduction of fertility. This work establishes the link between OsIMAs and OsHRZs, and develops a new strategy for Fe fortification in rice.

molecular biology↗

bioRxiv2022

Cohesin mutation sensitizes cancer cells to anti-PD-1 therapy through endogenous retrovirus-mediated PD-L1 upregulation

Immune checkpoint therapy shows impressive and durable clinical responses in cancer patients, but the genetic determinants that enable cancer cells to respond to anti-PD-1 therapy are still elusive. Herein, we identified that NIPBL deficiency promotes endogenous retrovirus (ERV) expression in tumour cells, which in turn inactivates CD8+ tumour-infiltrating lymphocytes (TILs) via the PD-L1/PD-1 inhibitory checkpoint pathway. Mechanistically, NIPBL deficiency impairs DNMT1 transcription, preventing DNMT1 from suppressing ERV expression in tumour cells; ERVs stimulate PD-L1 expression by inducing the STAT2-IRF9 complex, a downstream event of double-stranded RNA (dsRNA)-MAVS-IRF3 signalling, and thereby suppress CD8 TIL-mediated immunity. An anti-PD-1 monoclonal antibody achieved remarkable therapeutic effects in Nipbl-deficient syngeneic tumour models and improved host survival by eliciting an antitumour memory immune response. Cancer patients harbouring mutations of cohesin subunits and regulators plus DNMT1 had significantly better responses to anti-PD-1 therapy than their non-mutated counterparts did. Our study reveals a novel mechanism by which cohesin complex deregulation stimulates ERV expression by impairing DNMT1 expression and fosters an immunosuppressive tumour microenvironment by activating the PD-L1/PD-1 inhibitory checkpoint.

cancer biology↗

bioRxiv2022

Omission responses in field potentials but not spikes in rat auditory cortex

Non-invasive recordings of gross neural activity in humans often show responses to omitted stimuli in steady trains of identical stimuli. This has been taken as evidence for the neural coding of prediction or prediction error. However, evidence for such omission responses from invasive recordings of cellular-scale responses in animal models is scarce. Here, we sought to characterise omission responses using extracellular recordings in the auditory cortex of anaesthetised rats. We profiled omission responses across local field potentials (LFP), analogue multiunit activity (AMUA), and single/multi-unit spiking activity, using stimuli that were fixed-rate trains of acoustic noise bursts where 5% of bursts were randomly omitted. Significant omission responses were observed in LFP and AMUA signals, but not in spiking activity. These omission responses had a lower amplitude and longer latency than burst-evoked sensory responses, and omission response amplitude increased as a function of the number of preceding bursts. Contrary to theories of neural entrainment, rhythmic stimulus presentation did not increase low-frequency phase-locking of neural activity specific to the stimulus presentation rate. Together, our findings show that omission responses are observed in LFP and AMUA signals, with laminar specificity, but are not observed in spiking activity, and do not show evidence for low-frequency phase locking. This has implications for models of cortical processing that require many neurons to encode prediction error in their spike output, and may have some consistency with representation of error in dendrites electrotonically distant from the soma.

neuroscience↗

bioRxiv2022

Dissociable neural correlates of multisensory coherence and selective attention

Previous work has demonstrated that performance in an auditory selective attention task can be enhanced or impaired, depending on whether a task-irrelevant visual stimulus is temporally coherent with a target auditory stream or with a competing distractor. However, it remains unclear how audiovisual (AV) temporal coherence and auditory selective attention interact at the neurophysiological level. Here, we measured neural activity using electroencephalography (EEG) while participants performed an auditory selective attention task, detecting deviants in a target audio stream. The amplitude envelope of the two competing auditory streams changed independently, while the radius of a visual disc was manipulated to control the audiovisual coherence. Analysis of the neural responses to the sound envelope demonstrated that auditory responses were enhanced independently of the attentional condition: both target and masker stream responses were enhanced when temporally coherent with the visual stimulus. In contrast, attention enhanced the event-related response (ERP) evoked by the transient deviants, independently of AV coherence. Finally, we identified a spatiotemporal component of the ERP, likely originating from the superior temporal gyrus and the frontoparietal network, in which both attention and coherence synergistically modulated ERP amplitude. These results provide evidence for dissociable neural signatures of bottom-up (coherence) and top-down (attention) effects in the AV object formation.

neuroscience↗

bioRxiv2021

A large-sample crisis? Exaggerated false positives by popular differential expression methods

We report a surprising phenomenon about identifying differentially expressed genes (DEGs) from population-level RNA-seq data: two popular bioinformatics methods, DESeq2 and edgeR, have unexpectedly high false discovery rates (FDRs). Via permutation analysis on an immunotherapy RNA-seq dataset, we observed that DESeq2 and edgeR identified even more DEGs after samples condition labels were randomly permuted. Motivated by this, we evaluated six DEG identification methods (DESeq2, edgeR, limma-voom, NOISeq, dearseq, and the Wilcoxon rank-sum test) on population-level RNA-seq datasets. We found that the FDR control was often failed by the three popular parametric methods--DESeq2, edgeR, and limma-voom-- and the new non-parametric method dearseq. In particular, the actual FDRs of DESeq2 and edgeR sometimes exceeded 20% when the target FDR threshold was only 5%. Although NOISeq, a non-parametric method used by GTEx, controlled the FDR better than the other four methods did, its power was much lower than that of the Wilcoxon rank-sum test, a classic nonparametric test that consistently controlled the FDR and achieved good power in our evaluation. Based on these results, for population-level RNA-seq studies, we recommend the Wilcoxon rank-sum test.

bioinformatics↗

bioRxiv2021

Evolution of a costly immunity to cestode parasites is a pyrrhic victory

Parasites impose fitness costs on their hosts. Biologists therefore tend to assume that natural selection favors infection-resistant hosts. Yet, when the immune response itself is costly, theory suggests selection may instead favor loss of resistance. Immune costs are rarely documented in nature, and there are few examples of adaptive loss of resistance. Here, we show that when marine threespine stickleback colonized freshwater lakes they gained resistance to the freshwater-associated tapeworm, Schistocephalus solidus. Extensive peritoneal fibrosis and inflammation contribute to suppression of cestode growth and viability, but also impose a substantial cost of reduced fecundity. Combining genetic mapping and population genomics, we find that the immune differences between tolerant and resistant populations arise from opposing selection in both populations acting, respectively, to reduce and increase resistance consistent with divergent optimization. One Sentence SummaryRecently-evolved freshwater populations of stickleback frequently evolve increased resistance to tapeworms, involving extensive fibrosis that suppresses parasite growth; because this fibrosis greatly reduces fish fecundity, in some freshwater populations selection has favored an infection-tolerant strategy with fibrosis suppression.

evolutionary biology↗

bioRxiv2021

ProXs drive the formation of membraneless organelles in plants

Membraneless organelles (MLOs) are non-membranous structures inside cells that organize cellular space and processes. The recent discovery that MLOs can be assembled via liquid-liquid phase separation (LLPS) advanced our understanding of these structures. However, the proteins that are capable of forming MLOs are largely unknown, especially in plants. In this study, we developed a method to identify proteins that we referred as ProXs (Proteins enriched by b-isoX) in Arabidopsis. Heterologous expression in yeast cells showed that most ProXs were capable of forming MLOs autonomously. We applied this method to several model and crop species including early and higher plants. This allowed us to generate an atlas of ProXs for studying plant MLOs. Analysis of ProXs from different species revealed high degree of conservation, supporting that they play important roles in cellular functions and are positively selected during evolution. Our method will be a valuable tool to characterize novel MLOs from desired cells and the data generated in present study will be instrumental for the plant research community to investigate MLO biology.

plant biology↗

bioRxiv2021

Notch-Induced Endoplasmic Reticulum-Associated Degradation Governs Thymocyte β-Selection

Signals from the pre-T cell receptor and Notch coordinately instruct {beta}-selection of CD4-CD8- double negative (DN) thymocytes to generate {beta} T cells in the thymus. However, how these signals ensure a high-fidelity proteome and safeguard the clonal diversification of the pre- selection TCR repertoire given the considerable translational activity imposed by {beta}-selection is largely unknown. Here, we identify the endoplasmic reticulum (ER)-associated degradation (ERAD) machinery as a critical proteostasis checkpoint during {beta}-selection. Expression of the SEL1L-HRD1 complex, the most conserved branch of ERAD, is directly regulated by the transcriptional activity of the Notch intracellular domain. Deletion of Sel1l impaired DN3 to DN4 thymocyte transition and severely impaired {beta} T cell development. Mechanistically, Sel1l deficiency induced unresolved ER stress that triggered thymocyte apoptosis through the PERK pathway. Accordingly, genetically inactivating PERK rescued T cell development from Sel1l- deficient thymocytes. Our study reveals a critical developmental signal controlled proteostasis mechanism that enforces T cell development to ensure a healthy adaptive immunity.

immunology↗

bioRxiv2021

An NCCN-IPI based immune-related gene prognostic model for diffuse large B-cell lymphoma

BackgroundInternational Prognostic Index (IPI) was widely used to better discriminate prognosis of patients with diffuse large B-cell lymphoma (DLBCL). However, there is a significant need to identify novel valuable biomarkers in the context of targeted therapies, such as immune checkpoint blockade (ICB) therapy. MethodsGene expression data and clinical information of DLBCL were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets. 371 immune-related hub genes in DLBCL patients with different IPI levels were identified by weighted gene co-expression network analysis (WGCNA), and 8 genes were selected to construct an IPI-based immune prognostic model (IPI-IPM). Afterward, the genetic, somatic mutational and molecular profiles of IPI-IPM subgroups were analyzed, as well as the potential clinical response of ICB in different IPI-IPM subgroups. ResultsThe IPI-IPM was constructed based on the expression of CMBL, TLCD3B, SYNDIG1, ESM1, EPHA3, HUNK, PTX3 and IL12A, where high-risk patients had shorter overall survival (OS) than low-risk patients, consistent with the results in the GEO cohorts. The comprehensive results showed that high IPI-IPM risk scores were correlated with immune-related signaling pathways, high KMT2D and CD79B mutation rates, as well as up-regulation of inhibitory immune checkpoints including PD-L1, BTLA and SIGLEC7, indicating more potential response to ICB therapy. ConclusionThe IPI-IPM has independent prognostic significance for DLBCL patients, which provides an immunological perspective to elucidate the mechanisms on tumor progression, also sheds a light on developing immunotherapy for DLBCL.

bioinformatics↗