Biology subjects

Zheng, C.

Publications and source records attributed to Zheng, C..

At least 109 records · Page 6Linked to original sources

bioRxiv2022

ReDisX: a Continuous Max Flow-based framework to redefine the diagnosis of diseases based on identified patterns of genomic signatures

Diseases originate at the molecular-genetic layer, manifest through altered biochemical homeostasis, and develop symptoms later. Hence symptomatic diagnosis is inadequate to explain the underlying molecular-genetic abnormality and individual genomic disparities. The current trends include molecular-genetic information relying on algorithms to recognize the disease subtypes through gene expressions. Despite their disposition toward disease-specific heterogeneity and cross-disease homogeneity, a gap still exists to describe the extent of homogeneity within the heterogeneous subpopulation of different diseases. They are limited to obtaining the holistic sense of the whole genome-based diagnosis resulting in inaccurate diagnosis and subsequent management. To fill those gaps, we proposed ReDisX framework, a scalable machine learning algorithm that uniquely classifies patients based on their genomic signatures. It was deployed to re-categorizes the patients with rheumatoid arthritis and coronary artery disease. It reveals heterogeneous subpopulations within a disease and homogenous subpopulations across different diseases. Besides, it identifies GZMB as a subpopulation-differentiation marker that plausibly serves as a prominent indicator for GZMB-targeted drug repurposing. The ReDisX framework offers a novel strategy to redefine disease diagnosis through characterizing personalized genomic signatures. It may rejuvenate the landscape of precision and personalized diagnosis, and a clue to drug repurposing.

bioinformatics↗

bioRxiv2022

Differential gene expression profiling reveals potential biomarkers and pharmacological compounds against SARS-CoV-2: insights from machine learning and bioinformatics approaches

SARS-CoV-2 continues to spread and evolve worldwide, despite intense efforts to develop multiple vaccines and therapeutic options against COVID-19. Moreover, the precise role of SARS-CoV-2 in the pathophysiology of the nasopharyngeal tract (NT) is still unfathomable. Therefore, we used the machine learning methods to analyze 22 RNA-seq datasets from COVID-19 patients (n=8), recovered individuals (n=7), and healthy individuals (n=7) to find disease-related differentially expressed genes (DEGs). In comparison to healthy controls, we found 1960 and 153 DEG signatures in COVID-19 patients and recovered individuals, respectively. We compared dysregulated DEGs to detect critical pathways and gene ontology (GO) connected to COVID-19 comorbidities. In COVID-19 patients, the DEG- miRNA and DEG-transcription factors (TFs) interactions network analysis revealed that E2F1, MAX, EGR1, YY1, and SRF were the most highly expressed TFs, whereas hsa-miR-19b, hsa-miR-495, hsa-miR-340, hsa-miR-101, and hsa-miR-19a were the overexpressed miRNAs. Three chemical agents (Valproic Acid, Alfatoxin B1, and Cyclosporine) were abundant in COVID-19 patients and recovered individuals. Mental retardation, mental deficit, intellectual disability, muscle hypotonia, micrognathism, and cleft palate were the significant diseases associated with COVID-19 by sharing DEGs. Finally, we detected DEGs impacted by SARS-CoV-2 infection and mediated by TFs and miRNA expression, indicating that SARS-CoV-2 infection may contribute to various comorbidities. These pathogenetic findings can provide some crucial insights into the complex interplay between COVID-19 and the recovery stage and support its importance in the therapeutic development strategy to combat against COVID-19 pandemic. IMPORTANCEDespite it has now been over two years since the beginning of the COVID-19 pandemic, many crucial questions about SARS-CoV-2 infection and the different COVID-19 symptoms it causes remain unresolved. An intriguing question about COVID-19 is how SARS-CoV-2 interplays with the host during infection and how SARS-CoV-2 infection can cause so many disease symptoms. Our analysis of three different datasets (COVID-19, recovered, and healthy) revealed significantly higher DEGs in COVID-19 patients than recovered humans and healthy controls. Some of these DEGs were found to be co-expressed in both COVID-19 patients. They recovered humans supporting the notion that DEGs level is directly correlated with the viral load, disease progression, and different comorbidities. The protein-protein interaction consisting of 24 nodes and 72 edges recognized eight hub-nodes as potential hub-proteins (i.e., RPL4, RPS4X, RPL19, RPS12, RPL19, EIF3E, MT-CYB, and MT-ATP6). Protein-chemical interaction analysis identified three chemical agents (e.g., Valproic Acid, Alfatoxin B1, and Cyclosporine) enriched in COVID-19 patients and recovered individuals. Mental retardation, mental deficiency, intellectual disability, muscle hypotonia, micrognathism, and cleft palate were the significant diseases associated with COVID-19 by sharing DEGs.

bioinformatics↗

bioRxiv2022

Drug design and repurposing with a sequence-to-drug paradigm

Drug development based on target proteins has been a successful approach in recent decades. A conventional structure-based drug design pipeline is a complex, human-engineered pipeline with multiple independently optimized steps. Advances in end-to-end differentiable learning suggest the potential benefits of similarly reformulating drug design. Here, we proposed a new sequence-to-drug paradigm that discovers drug-like small-molecule modulators directly from protein sequences and validated this concept for the first time in three stages. First, we designed TransformerCPI2.0 as a core tool for the sequence-to-drug paradigm, which exhibited competitive performance with conventional structure-based drug design approaches. Second, we validated the binding knowledge that TransformerCPI2.0 has learned. Third, we applied a sequence-to-drug paradigm to discover new hits for E3 ubiquitin-protein ligases: speckle-type POZ protein (SPOP), ring finger protein 130 (RNF130) which does not have a 3D structure, and repurposed proton pump inhibitors (PPIs) for ADP-ribosylation factor 1 (ARF1). This first proof of concept shows that the sequence-to-drug paradigm is a promising direction for drug development.

molecular biology↗

bioRxiv2022

Dynamic evolution of recently duplicated genes in Caenorhabditis elegans

As a major origin of evolutionary novelties, gene duplication is a widespread phenomenon across species. However, the evolutionary force that determines the fate of duplicate genes is still under debate. Here, we studied the functional evolution of duplicate genes at both macroevolution and microevolution scales using the genomic sequences of eleven Caenorhabditis species and 773 C. elegans wild isolates. We found that compared to older duplicate genes and single-copy genes, recently duplicated gene copies showed rapid turnover, large genetic diversity, and signs of balancing and positive selection within the species. Young duplicate genes have low basal expression restricted to a few tissues but show highly responsive expression towards pathogenic infections. Recently duplicated genes are enriched in chemosensory perception, protein degradation, and innate immunity, implicating their functions in enhancing adaptability to external perturbations. Importantly, we found that young duplicate genes are rarely essential, while old duplicate genes have the same level of essentiality as singletons, suggesting that essentiality develops over a long time. Together, our work in C. elegans demonstrates that natural selection shapes the dynamic evolutionary trajectory of duplicate genes. SignificanceThe "evolution by gene duplication" theory suggests that gene duplications provide the genetic materials for mutation and selection to act upon, expand the repertoire of molecular functions, and enable evolutionary novelty. Although various models were proposed to describe the fate of duplicate genes, empirical evidence for these models is limited. We analyzed gene duplications in eleven nematode Caenorhabditis species and studied the intraspecific variation of these duplicate genes among C. elegans wild strains. We found that compared to older duplicate gens and single-copy genes, recently duplicated genes show rapid turnover, large genetic diversity, and strong signs of balancing and positive selection but rarely develop essential functions. Our results describe the evolutionary trajectory of duplicate genes shaped by natural selection.

evolutionary biology↗

bioRxiv2022

A snapshot of the root phenotyping landscape in 2021

Root phenotyping describes methods for measuring root properties, or traits. While root phenotyping can be challenging, it is advancing quickly. In order for the field to move forward, it is essential to understand the current state and challenges of root phenotyping, as well as the pressing needs of the root biology community. In this letter, we present and discuss the results of a survey that was created and disseminated by members of the Graduate Student and Postdoc Ambassador Program at the 11th symposium of the International Society of Root Research. This survey aimed to (1) provide an overview of the objectives, biological models and methodological approaches used in root phenotyping studies, and (2) identify the main limitations currently faced by plant scientists with regard to root phenotyping. Our survey highlighted that (1) monocotyledonous crops dominate the root phenotyping landscape, (2) root phenotyping is mainly used to quantify morphological and architectural root traits, (3) 2D root scanning/imaging is the most widely used root phenotyping technique, (4) time-consuming tasks are an important barrier to root phenotyping, (5) there is a need for standardised, high-throughput methods to sample and phenotype roots, particularly under field conditions, and to improve our understanding of trait-function relationships.

scientific communication and education↗

bioRxiv2022

Assembly and comparative analysis of the complete mitochondrial genome of three Macadamia species (M. integrifolia, M. ternifolia and M. tetraphylla)

BackgroundMacadamia is a true dicotyledonous plant that thrives in a mild, humid, low wind environment. It is cultivated and traded internationally due to its high-quality nuts thus, has significant development prospects and scientific research value. However, information on the genetic resources of Macadamia spp. remains scanty. ResultsThe mitochondria (mt) genomes of three economically important Macadamia species, Macadamia integrifolia, M. ternifolia and M. tetraphylla, were assembled through the Illumina sequencing platform. The results showed that each species has 71 genes, including 42 protein-coding genes, 26 tRNAs, and 3 rRNAs. Repeated sequence analysis, RNA editing site prediction, and analysis of genes migrating from chloroplast (cp) to mt were performed in the mt genomes of the three Macadamia species. Phylogenetic analysis based on the mt genome of the three Macadamia species and 35 other species was conducted to reveal the evolution and taxonomic status of Macadamia. Furthermore, the characteristics of the plant mt genome, including genome size and GC content, were studied through comparison with 36 other plant species. The final non-synonymous (Ka) and synonymous (Ks) substitution analysis showed that most of the protein-coding genes in the mt genome underwent negative selections, indicating their importance in the mt genome. ConclusionThe findings of this study provide a better understanding of the Macadamia genome and will inform future research on the genus.

genomics↗

bioRxiv2022

FRET monitoring of transcription factor activities in living bacteria

Bacteria adapt to the constantly changing environments largely by transcriptional regulation through the activities of various transcription factors (TFs). However, techniques that monitor the in situ TF-promoter interactions in living bacteria are lacking. Herein, we developed a whole-cell TF-promoter binding assay based on the intermolecular Forster resonance energy transfer (FRET) between a fluorescent unnatural amino acid CouA which is genetically encoded into defined sites in TFs and the live cell fluorescent nucleic acid stain SYTO 9. We show that this new FRET pair monitors the intricate TF-promoter interactions elicited by various types of signal transduction systems with specificity and sensitivity. Furthermore, the assay is applicable to identify novel modulators of the regulatory systems of interest and monitor TF activities in bacteria colonized in C. elegans. In conclusion, we established a tractable and sensitive TF-promoter binding assay in living bacteria which not only complements currently available approaches for DNA-protein interactions but also provides novel opportunities for functional annotation of bacterial signal transduction systems and studies of the bacteria-host interface.

molecular biology↗

bioRxiv2021

Determination of nuclear position by the arrangement of actin filaments using deep generative networks

The cell nucleus is a dynamic structure that changes locales during cellular processes such as proliferation, differentiation, or migration1, and its mispositioning is a hallmark of several disorders2,3. As with most mechanobiological activities of adherent cells, the repositioning and anchoring of the nucleus are presumed to be associated with the organization of the cytoskeleton, the network of protein filaments providing structural integrity to the cells4. However, this correlation between cytoskeleton organization and nuclear position has not, to date, been demonstrated, as it would require the parameterization of the extraordinarily intricate cytoskeletal fiber arrangements. Here, we show that this parameterization and demonstration can be achieved outside the limits of human conceptualization, using generative network and raw microscope images, relying on machine-driven interpretation and selection of parameterizable features. The developed transformer-based architecture was able to generate high-quality, completed images of more than 8,000 cells, using only information on actin filaments, predicting the presence of a nucleus and its exact localization in more than 70 per cent of instances. Our results demonstrate one of the most basic principles of mechanobiology with a remarkable level of significance. They also highlight the role of deep learning as a powerful tool in biology beyond data augmentation and analysis, capable of interpreting--unconstrained by the principles of human reasoning--complex biological systems from qualitative data.

bioinformatics↗

bioRxiv2021

Little heterosis found in Diploid Hybrid Potato

Hybrid potato breeding has become a novel alternative to con-ventional potato breeding allowing breeders to overcome intractable barriers (e.g. tetrasomic inheritance, masked deleterious alleles, obligate clonal propagation) with the benefit of seed-based propagule, flexible population design, and the potential of hybrid vigour. Until now, however, no formal inquiry has adequately examined the relevant genetic components for complex traits in hybrid potato populations. In this present study, we use a two-step modelling approach to estimate the relevant variance components to assess the magnitude of the general and specific combining abilities (GCA and SCA, respectively) in diploid hybrid potato (DHP). SCA effects were identified for all yield components studied here warranting evidence of non-additive genetic effects in hybrid potato yield. However, the estimated GCA effects were on average two times larger than their respective SCA quantile across all yield phenotypes. Tuber number GCAs and SCAs were found to be highly correlated with total yields genetic components. Tuber volume appearing under-selected in this population. The prominence of additive effects found for all traits presents evidence that breeders can perform hybrid potato evaluation using the mid-parent value alone. Heterotic vigour stands be useful in bolstering simpler traits but this will be very dependent on the target market of a population. This study represents the first diallel analysis of its kind in diploid potato using material derived from a commercial hybrid breeding programme.

genetics↗

bioRxiv2021

Regulation of drought tolerance in Arabidopsis involves PLATZ4-mediated transcriptional suppression of PIP2;8

PLATZ transcription factors play important roles in plant growth, development, and biotic and abiotic stress responses. However, how PLATZ regulates plant drought tolerance and ABA sensitivity remains largely unknown. Here, we show that PLATZ4 increases drought tolerance and ABA sensitivity in Arabidopsis thaliana by suppressing the expression of PIP2;8, DEG3, At1g33840 and At3g01345, while upregulating the expression of PR1, ABI3, ABI4 and ABI5. Moreover, PLATZ4 directly binds A/T-rich sequences within the PIP2;8 promoter but not ABI3, ABI4 and ABI5 promoters. Consistent with this, PIP2;8 acts epistatically to PLATZ4. Furthermore, the aquaporin activity of PIP2;8 was confirmed in Xenopus laevis oocytes and yeast cells in response to osmotic stress. Analysis of water loss of seedlings overexpressing PIP2;8 or lacking PIP2;8 function indicated that PIP2;8-mediated water flow is particularly active in response to drought stress in planta. Accordingly, stomatal closure was enhanced in pip2;8 mutants but reduced in PIP2;8-overexpressing plants. In platz4 mutant and PLATZ4-overexpressing plants, water loss and stomatal closure changed oppositely to those in pip2;8 mutants and PIP2;8-overexpressing plants, respectively. In addition, the interaction between PLATZ4 and AITR6 was confirmed by several assays, and the binding of PIP2;8 promoter by PLATZ4 was strengthened by an interaction with AITR6. Collectively, our findings reveal that PLATZ4 interacts with AITR6 to increase ABA sensitivity and drought tolerance in Arabidopsis by upregulating expression of PR1, ABI3, ABI4 and ABI5 while inhibiting the expression of PIP2;8 and associated genes. One sentence summaryPLATZ4 interacted with AITR6 to increase drought tolerance and ABA sensitivity in Arabidopsis thaliana by directly bind A/T-rich sequences within the plasma membrane aquaporin (PIP)2;8 promoter.

plant biology↗

bioRxiv2021

Development of a flexible split prime editor using truncated reverse transcriptase

Prime Editor (PE) has tremendous promise for gene therapy. However, it remains a challenge to deliver PE (>6.3 kb) in vivo. Although PE can be split into two fragments and delivered using dual adeno-associated viruses (AAVs), choice of split sites within Cas9 - which affects editing efficiency - is limited due to the large size of PE. Furthermore, the potential effect of overexpressing RT in mammalian cells is largely unknown. Here, we developed a compact PE with complete deletion of the RNase H domain of reverse transcriptase (RT), which showed comparable editing to full-length PE. Using compact PE, we tested the effect of 4 different Cas9 split sites and found that the Glu 573 split site supports robust editing (up to 93% of full-length PE). The compact PE, but not PE2, abolished its binding to eRF1 and showed minimal effect on stop codon readthrough, which therefore might reduce the effects on protein biosynthesis. This study identifies a safe and efficient compact PE2 that enables flexible split-PE design to facilitate efficient delivery in vivo and advance the utility of prime editing.

genetics↗

bioRxiv2021

MicroRNA-202 prevents precocious spermatogonial differentiation and meiotic initiation during mouse spermatogenesis

Spermatogonial differentiation and meiotic initiation during spermatogenesis are tightly regulated by a number of genes including those coding enzymes for miRNA biogenesis. However, whether and how single miRNAs regulate these processes remain unclear. Here, we report that miR-202, a member of the let-7 family, prevents precocious spermatogonial differentiation and meiotic initiation in spermatogenesis by regulating the timely expression of many genes including those for other key regulators. In miR-202 knockout (KO) mice, the undifferentiated spermatogonial pool is reduced, ultimately causing agametic seminiferous tubules. SYCP3, STRA8 and DMRT6 are expressed earlier in KO mice than in wild-type (WT) littermates, and Dmrt6 mRNA is a direct target of miR-202-5p. Moreover, the precocious spermatogonial differentiation and meiotic initiation were also observed in KO spermatogonial stem cells when cultured and induced in vitro, and could be rescued by the knockdown of Dmrt6. Therefore, we have not only shown that miR-202 is a novel regulator of meiotic initiation but also added a new module to the underlying regulatory network. Summary statementA single miRNA, miR-202, prevents precocious differentiation and meiotic initiation during spermatogenesis. miR-202, DMRT6 and STRA8 act together as a novel module in the regulatory network of meiotic initiation.

developmental biology↗

bioRxiv2021

A metabolically stable PET tracer for imaging synaptic vesicle protein 2A: Synthesis and preclinical characterization of SDM-16

PurposeTo investigate the synaptic vesicle glycoprotein 2A (SV2A) expression in the whole central nervous system and peripheral tissues, a metabolically stable SV2A radiotracer is desirable to minimize a potential confounding effect of radiometabolites. The aim of this study was to develop and evaluate a metabolically stable SV2A radiotracer, [18F]SDM-16, in nonhuman primate brains. MethodsThe racemic SDM-16 (4-(3,5-difluorophenyl)-1-((2-methyl-1H-imidazol-1-yl)methyl)pyrrolidin-2-one) was synthesized and assayed for in vitro SV2A binding affinity. We synthesized the enantiopure [18F]SDM-16 using the corresponding arylstannane precursor. Nonhuman primate brain PET was performed on a FOCUS 220 system. Arterial blood was drawn for metabolite analysis and construction of plasma input function. Regional time-activity curves (TACs) were evaluated with the one-tissue compartment (1TC) model to obtain the volume of distribution (VT). Binding potential (BPND) was calculated using either the nondisplaceable volume of distribution (VND) or the centrum semiovale (CS) as the reference region. ResultsRacemic SDM-16 was synthesized in 3 steps with 44% overall yield and has high affinity (Ki = 3.7 nM) to human SV2A. [18F]SDM-16 was prepared in greater than 99% radiochemical and enantiomeric purity. This radiotracer displayed high specific binding in brain and was metabolically more stable than other SV2A PET tracers. The plasma free fraction (fP) of [18F]SDM-16 was 69%, which was higher than those of [11C]UCB-J (46%), [18F]SynVesT-1 (43%), [18F]SynVesT-2 (41%), and [18F]UCB-H (43%). The TACs were well described with the 1TC. The averaged test-retest variability (TRV) was -9{+/-}8%, and averaged absolute TRV (aTRV) was 10{+/-}7% for all analyzed brain regions. ConclusionWe have successfully synthesized a metabolically stable and high affinity SV2A PET tracer, [18F]SDM-16, which showed high specific and reversible binding in the NHP brain. [18F]SDM-16 may have potential application in the visualization and quantification of SV2A beyond the brain.

neuroscience↗

bioRxiv2021

The cardiac STAT3 intercalated disc specific expression in tail suspension rat

BackgroundThe cardiovascular system is significantly agitated by loss of gravity. In microgravity, the body fluids shift toward the thoracic cavity, induced the heart becomes more spherical. This further increased the cardiac preload with an increasing of transmural central venous pressure, affects the right heart ventricles to tolerating the enhanced preload on the right ventricular wall. MethodIn this study we investigated the rat right ventricle remodeling in simulating persistent microgravity by using tail-suspension model, examined the remolding of the heart and the specific STAT3 expression in right heart myocardium. ResultThe results indicated that microgravity induced heart remodeling included a significant increasing of the ventricular weight in the left. However, the right ventricle was not increased significantly in the microgravity simulation rats. The histological study demonstrated that the outstanding development on right ventricular wall which included the gap junction remodeling and STAT3 signaling protein specific accumulation in the right ventricles. ConclusionThe results existed that the right cardiac ventricle has a distinctive remodeling process during microgravity simulation which was not the muscular hypertrophy and relative weight increasing, but manifested the STAT3 accumulation and the electrical gap junction remodeling. The effect of microgravity induced right ventricle remodeling and the STAT3 specific accumulation can be used for multi-purpose research.

physiology↗

bioRxiv2021

Chromatin-interacting transposon RNAs linking to the core trans-inhibition circuitry for embryonic stem cell identity

Transposable DNA sequences constitute more than half of the human and mouse genomes. A large number of non-coding RNAs, named as transposon RNAs, are derived from these transposable elements. The cis-regulatory function of transposable DNA elements, such as LINE-1 and Alu has been largely explored. But the biological roles of transposon RNAs arent well understood. Here, investigations of RNA-chromatin interactions provide us with comprehensive evidence that specific families of transposon RNAs play roles in trans-regulation linking to the core inhibition circuitry for embryonic stem cell identity. Alternative modes of the RNA-DNA hybrid duplex and protein-recruited RNA scaffold are required for the regulatory activities of transposon RNAs. LINE-1 RNAs co-locating with KAP1 form a negative feedback loop stabilizing the transcription of LINE-1 DNA elements via RNA-DNA hybrids. In another way LINE-1 RNAs, together with the reprogramming three factors and Polycomb repressive complexes, participate in the inhibition on dozens of differentiation-relative genes.

genomics↗

bioRxiv2021

MicroRNA-202 safeguards meiotic progression by preventing premature degradation of REC8 mediated by separase

MicroRNAs (miRNAs) are believed to play important roles in mammalian spermatogenesis but the in vivo functions of single miRNAs in this highly complex developmental process remain unclear. Here, we reported that miR-202, a member of the let-7 family, played an important role in mouse spermatogenesis by phenotypic evaluation of miR-202 knockout (KO) mice. In miR-202 KO mice, germ cells underwent apoptosis. Multiple processes in meiosis I including synapsis and crossover formation were disrupted, and inter-sister chromatid synapses were detected. More importantly, we found that upon miR-202 KO, meiotic-specific cohesin protein REC8 was prematurely cleaved by precociously activated separase, whose mRNA was a direct target of miR-202-3p. Our findings identify miR-202 as a novel regulator of meiosis and contribute to the list of miRNAs that play specific and important roles in developmental processes.

developmental biology↗

bioRxiv2021

Genome-wide screen identifies curli amyloid fibril as a bacterial component promoting host neurodegeneration

Growing evidence indicate that gut microbiota play a critical role in regulating the progression of neurodegenerative diseases, such as Parkinsons disease (PD). The molecular mechanism underlying such microbe-host interaction is unclear. In this study, by feeding C. elegans expressing human -syn with E. coli knockout mutants, we conducted a genome-wide screen to identify bacterial genes that promote host neurodegeneration. The screen yielded 38 genes that fall into several genetic pathways, including curli formation, lipopolysaccharide assembly, adenosylcobalamin biosynthesis among others. We then focused on the curli amyloid fibril and found that genetically deleting or pharmacologically inhibiting the curli major subunit CsgA in E. coli reduced -syn-induced neuronal death, restored mitochondrial health, and improved neuronal functions. CsgA secreted by the bacteria colocalized with -syn inside neurons and promoted -syn aggregation through cross-seeding. Similarly, curli also promoted neurodegeneration in C. elegans models of AD, ALS, and HD and in human neuroblastoma cells.

neuroscience↗

bioRxiv2021

Mood and reward dynamics in human adolescent brain electrophysiology

Despite its omnipresence in everyday interactions and its importance for mental health, mood and its neuronal underpinnings are poorly understood. Computational models can help identify parameters affecting self-reported mood during mood induction tasks. Here we test if computationally modelled dynamics of self-reported mood during monetary gambling can be used to identify trial-by-trial variations in neuronal activity. To this end, we shifted mood in healthy (N=24) and depressed (N=30) adolescents by delivering individually tailored reward prediction errors whilst recording magnetoencephalography (MEG) data. Following a pre-registered analysis, we hypothesize that expectation (defined by previous reward outcomes) would be predictive of beta-gamma oscillatory power (25-40Hz), a frequency shown to modulate to reward feedback. We also hypothesize that trial variations in the evoked response to the presentation of gambling options and in source localized responses to reward feedback. Through our multilevel statistical analysis, we found confirmatory evidence that beta-gamma power is positively related to reward expectation during mood shifts, with possible localized sources in the posterior cingulate cortex. We also confirmed reward prediction error to be predictive of trial-level variations in the response of the paracentral lobule and expectation to have an effect on the cerebellum after presentation of gambling options. To our knowledge, this is the first study to relate fluctuations in mood on a minute timescale to variations in neural oscillations with noninvasive electrophysiology. Significance StatementBrain mechanisms underlying mood and its relationship with changes in reward contingencies in the environment are still elusive but could have a strong impact on our understanding and treatment of debilitating mood disorders. Building on a previously proposed computational mood model we use multilevel statistical models to find relationship between trial-by-trial variations in model components of mood and neural responses to rewards measured with non-invasive electrophysiology (MEG). Through confirmatory analysis we show that it is possible to observe relationships between trial variations in neural responses and computational parameters describing mood dynamics. Identifying the dynamics of mood and the neural processes it affects could pave the way for more effective neuromodulation treatments.

neuroscience↗