Biology subjects

Lyu, Y.

Publications and source records attributed to Lyu, Y..

At least 37 records · Page 2Linked to original sources

bioRxiv2023

Transfer of disulfide bond formation modules via yeast artificial chromosomes promotes the expression of heterologous proteins in Kluyveromyces marxianus

Kluyveromyces marxianus is a food-safe yeast with great potential for producing heterologous proteins. Improving the yield in K. marxianus remains a challenge, while incorporating large-scale functional modules poses a technical obstacle in engineering. To address these issues, linear and circular yeast artificial chromosomes of K. marxianus (KmYACs) were constructed and loaded with disulfide bond formation modules from Pichia pastoris or K. marxianus. These modules contained up to 7 genes with a maximum size of 15 kb. KmYACs carried telomeres either from K. marxianus or Tetrahymena. KmYACs were transferred successfully into K. marxianus and stably propagated without affecting the normal growth of the host, regardless of the type of telomeres and configurations of KmYACs. KmYACs increased the overall expressions of disulfide bond formation genes and significantly enhanced the yield of various heterologous proteins. In high-density fermentation, the use of KmYACs resulted in a glucoamylase yield of 16.8 g/L, the highest reported level to date in K. marxianus. Transcriptomic and metabolomic analysis of cells containing KmYACs suggested increased FAD biosynthesis, enhanced flux entering the TCA cycle and a preferred demand for lysine and arginine as features of cells overexpressing heterologous proteins. Consistently, supplementing lysine or arginine further improved the yield. Therefore, KmYAC provides a powerful platform for manipulating large modules with enormous potential for industrial applications and fundamental research. Transferring the disulfide bond formation module via YACs proves to be an efficient strategy for improving the yield of heterologous proteins, and this strategy may be applied to optimize other microbial cell factories. Impact StatementIn this study, yeast artificial chromosomes of K. marxianus (KmYACs) were constructed and successfully incorporating modules for large-scale disulfide bond formation. KmYACs were stably propagated in K. marxianus without compromising the normal growth of the host, irrespective of the selection of telomeres (either Tetrahymena or K. marxianus) and configuration (either linear or circular). KmYACs notably enhanced the expressions of various heterologous proteins, with further yield improvement by supplementing lysine or arginine in the medium. Our findings affirm KmYAC as a robust and versatile platform for transferring large-scale function modules, demonstrating immense potential for both industrial applications and fundamental research.

synthetic biology↗

bioRxiv2023

An automated archival single-nucleus total RNA sequencing platform mapping integrative and retrospective cell atlas of gliomas

Single-cell RNA sequencing (scRNA-seq) has dramatically transformed biomedical research within laboratory settings. It has been extensively employed to investigate the heterogeneity and plasticity of glioma, the most prevalent brain tumor. However, the clinical diagnosis and treatment of glioma remain complex and challenging, highlighting the need for comprehensive cancer research. Currently available scRNA-seq platforms are insufficient to fulfill the demands posed by large-scale clinical applications. Here, we present an automated high-throughput single-nucleus total RNA sequencing platform, known as AAsnRandom-seq. This platform integrates automated single-nucleus isolation and droplet barcoding systems with the random primer-based scRNA-seq chemistry, designed to accommodate a diverse range of sample types. The performance and versatility of AAsnRandom-seq are validated using over one hundred clinical FFPE and frozen samples. AAsnRandom-seq was applied to archival FFPE samples of various glioma subtypes, including rare clinical samples, and matched primary-recurrent glioblastomas (GBMs), delving into the comprehensive molecular characteristic of glioma at single-cell level. Abundant non-coding RNAs (ncRNAs) with distinct expression profiles within different glioma clusters are detected. Promising recurrence-related targets and pathways are identified from the matched primary-recurrent GBMs. AAsnRandom-seq holds significant application value on large-scale integrative and retrospective clinical research using archived specimens.

bioengineering↗

bioRxiv2023

optiPRM: A targeted immunopeptidomics LC-MS workflow with ultra-high sensitivity for the detection of mutation-derived tumor neoepitopes from limited input material

Personalized cancer immunotherapies such as vaccines and T cell receptor (TCR)-transgenic T cells rely on the presentation of tumor-specific peptides by human leukocyte antigen (HLA) class I molecules to cytotoxic T cells. Such neoepitopes can for example arise from somatic mutations and their identification is crucial for the rational design of new therapeutic interventions. For their detection by liquid chromatography mass spectrometry (LC-MS), we have developed a parameter optimization workflow to tune targeted assays for maximum detection sensitivity on a per peptide basis, termed optiPRM. Optimization of collision energy using optiPRM allows for improved detection of low abundant peptides that are very hard to detect using standard parameters. Applying this to immunopeptidomics, we detected a neoepitope in a patient-derived xenograft (PDX) from as little as 2.5x106 cells input. Application of the workflow on small patient tumor samples allowed for the detection of five mutation-derived neoepitopes in three patients. One neoepitope was confirmed to be recognized by patient T cells. In conclusion, we here present optiPRM, a targeted MS workflow reaching ultra-high sensitivity by per peptide parameter optimization, which allowed for the identification of actionable neoepitopes from sample sizes usually available in the clinic.

immunology↗

bioRxiv2023

Hostile attribution bias shapes neural synchrony in the left ventromedial prefrontal cortexduring ambiguous social narratives

Hostile attribution bias refers to the tendency to interpret social situations as intentionally hostile. While previous research has focused on its developmental origins and behavioral consequences, the underlying neural mechanisms remain underexplored. Here, we employed functional near infrared spectroscopy (fNIRS) to investigate the neural correlates of hostile attribution bias. While undergoing fNIRS, participants listened to and provided attribution ratings for 21 hypothetical scenarios where a characters actions resulted in a negative outcome for the listener. Ratings of hostile intentions were averaged to obtain a measure of hostile attribution bias. Using intersubject-representational similarity analysis, we found that participants with similar levels of hostile attribution bias exhibited higher levels of neural synchrony during narrative listening, suggesting shared interpretations of the scenarios. This effect was localized to the left ventromedial prefrontal cortex (VMPFC), and was particularly prominent in scenarios where the characters intentions were highly ambiguous. We then grouped participants into high and low bias groups based on a median split of their hostile attribution bias scores. A similarity-based classifier trained on the neural data classified participants as having high or low bias with 76% accuracy, indicating that the neural time courses during narrative listening was systematically different between the two groups. Furthermore, hostile attribution bias correlated negatively with attributional complexity, a measure of ones tendency to consider multifaceted causes when explaining behavior. Our study sheds light on the neural mechanisms underlying hostile attribution bias and highlights the potential of using fNIRS to develop non-intrusive and cost-effective neural markers of this socio-cognitive bias. Significance StatementInferring the intentions from behavior is crucial for adaptive social functioning. A predisposition towards interpreting intentions as hostile is a significant predictor of interpersonal conflict and aggressive tendencies. Using fNIRS, we found that individual differences in hostile attribution bias shaped neural synchrony in the VMPFC while processing real-world social situations. Additionally, we were able to distinguish between participants with high and low hostile attribution bias from neural activity time courses. These results reveal how subjective interpretations of social situations are influenced by hostile attribution bias and reflected in the temporal dynamics of the VMPFC. Our findings lay the groundwork for future studies aimed at understanding the neurobiological basis of socio-cognitive biases, as well as interventions aimed at mitigating these biases.

neuroscience↗

bioRxiv2023

Histone H3 serotonylation dynamics in dorsal raphe nucleus contribute to stress-induced gene expression and behavior

BackgroundMajor depressive disorder (MDD), along with related mood disorders, is a debilitating illness that affects millions of individuals worldwide. While chronic stress increases incidence levels of mood disorders, stress-mediated disruptions in brain function that precipitate these illnesses remain elusive. Serotonin-associated antidepressants (ADs) remain the first line of therapy for many with depressive symptoms, yet low remission rates and delays between treatment and symptomatic alleviation have prompted skepticism regarding precise roles for serotonin in the precipitation of mood disorders. Our group recently demonstrated that serotonin epigenetically modifies histone proteins (H3K4me3Q5ser) to regulate transcriptional permissiveness in brain. However, this phenomenon has not yet been explored following stress and/or AD exposures. MethodsWe employed a combination of genome-wide and biochemical analyses in dorsal raphe nucleus (DRN) of male and female mice exposed to chronic social defeat stress to examine the impact of stress exposures on H3K4me3Q5ser dynamics, as well as associations between the mark and stress-induced gene expression. We additionally assessed stress-induced regulation of H3K4me3Q5ser following AD exposures, and employed viral-mediated gene therapy to reduce H3K4me3Q5ser levels in DRN and examine the impact on stress-associated gene expression and behavior. ResultsWe found that H3K4me3Q5ser plays important roles in stress-mediated transcriptional plasticity. Chronically stressed mice displayed dysregulated H3K4me3Q5ser dynamics in DRN, with both AD- and viral-mediated disruption of these dynamics proving sufficient to rescue stress-mediated gene expression and behavior. ConclusionsThese findings establish a neurotransmission-independent role for serotonin in stress-/AD-associated transcriptional and behavioral plasticity in DRN.

neuroscience↗

bioRxiv2023

Widespread readthrough events in plants reveal unprecedented plasticity of stop codons

Stop codon readthrough (SCR), the decoding of a stop codon as a sense codon by the ribosome, has important biological implications but remains largely uncharacterized in plants. Here, we identified 1,009 SCR events in two monocots (maize, rice) and two dicots (soybean, Arabidopsis) using a proteogenomic strategy with 80 customized databases. SCR transcripts were mostly significantly shorter and had fewer components than non-SCR transcripts in two monocot plants, although these differences were not as significant in the dicots. Mass spectrometry evidence revealed that all three stop codons involved in SCR events could be recoded as 20 standard amino acids, some of which were also supported by suppressor transfer RNA analysis. In addition, we observed multiple functional signals in the C-terminal extensions of 34 maize SCR proteins, and characterized the structural and subcellular localization changes in the extended protein of BASIC TRANSCRIPTION FACTOR 3. Overall, our study not only demonstrates that SCR events are widespread in plants but also reveals the unprecedented recoding plasticity of stop codons, which provides important new insights into the flexibility of genetic decoding.

plant biology↗

bioRxiv2023

Flexible and site-specific manipulation of histones in live animals

Recent advances in protein engineering have provided a wealth of methods that allow for the site-specific manipulation of proteins in vitro and in cells. However, the efforts to expand these toolkits for use in live animals has been limited. Here, we report a new method for the semi-synthesis of site-specifically modified and chemically defined proteins in live animals. Importantly, we illustrate the usefulness of this methodology in the context of a challenging, chromatin bound N-terminal histone tail within rodent postmitotic neurons located in ventral striatum (Nucleus Accumbens/NAc). This approach provides the field with a precise and broadly applicable methodology for manipulating histones in vivo, thereby serving as a unique template towards examining chromatin phenomena that may mediate transcriptomic and physiological plasticity within mammals.

biochemistry↗

bioRxiv2023

CDK4/6 inhibition enhances SHP2 inhibitor efficacy and is dependent upon restoration of RB function in malignant peripheral nerve sheath tumors

Malignant peripheral nerve sheath tumors (MPNST) are highly aggressive soft tissue sarcomas with limited treatment options, and novel effective therapeutic strategies are desperately needed. We observe anti-proliferative efficacy of genetic depletion or pharmacological inhibition using the clinically available SHP2 inhibitor (SHP2i) TNO155. Our studies into the signaling response to SHP2i reveal that resistance to TNO155 is partially mediated by reduced RB function, and we therefore test the addition of a CDK4/6 inhibitor (CDK4/6i) to enhance RB activity and improve TNO155 efficacy. In combination, TNO155 attenuates the adaptive response to CDK4/6i, potentiates its anti-proliferative effects, and converges on enhancement of RB activity, with greater suppression of cell cycle and inhibitor-of-apoptosis proteins, leading to deeper and more durable anti-tumor activity in in vitro and in vivo patient-derived models of MPNST, relative to either single agent. Overall, our study provides timely evidence to support the clinical advancement of this combination strategy in patients with MPNST and other tumors driven by loss of NF1.

cancer biology↗

bioRxiv2023

Low level of antioxidant capacity biomarkers but not target overexpression predicts vulnerability to ROS-inducing drugs

Despite a strong rationale for why cancer cells are susceptible to redox-targeting drugs, such drugs often face tumor resistance or dose-limiting toxicity in preclinical and clinical studies. An important reason is the lack of specific biomarkers to better select susceptible cancer entities and stratify patients. Using a large panel of lung cancer cell lines, we identified a set of "antioxidant-capacity" biomarkers (ACB), which were tightly repressed, partly by STAT3 and STAT5A/B in sensitive cells, rendering them susceptible to multiple redox-targeting and ferroptosis-inducing drugs. Contrary to expectation, constitutively low ACB expression was not associated with an increased steady state level of reactive oxygen species (ROS) but a high level of nitric oxide, which is required to sustain high replication rates. Using ACBs, we identified cancer entities with a high percentage of patients with favorable ACB expression pattern, making it likely that more responders to ROS-inducing drugs could be stratified for clinical trials.

cancer biology↗

bioRxiv2022

Increased public health threat of avian-origin H3N2 influenza virus during evolution in dogs

Influenza A viruses in animal reservoirs repeatedly cross species barrier to infect humans. Once an animal-borne virus with novel antigenicity acquired the efficient human to human transmissibility, it will become epidemic in the population. Dogs are the closest animal companions to humans and canine respiratory tract expresses both SA2,3-(avian type) and 2,6-Gal (human type) receptors. However, the role of dogs in the ecology of influenza viruses is unclear. H3N2 avian influenza viruses transmitted to dogs around 2006 and have formed stable lineages. The long-term epidemic of avian-origin H3N2 virus in canine offers the best models to investigate the effect of dogs on the evolution of influenza viruses. Here, we carried out a systematic and comparative identification of the biological characteristics of H3N2 canine influenza viruses (CIVs) isolated in the worldwide over 10 years. We found that during the adaptation of H3N2 CIVs to dogs, H3N2 CIVs became to recognize the human-like SA2,6-Gal receptor, gradually increased HA acid stability and replication ability in human airway epithelial cells, and acquired a 100% transmission rate via respiratory droplet in ferret model, which were essential hallmarks of being adapted to humans. We also identified that the frequency of substitutions related to human adaptation has gradually increased in H3N2 CIVs, and determined four cumulative molecular changes responsible for the increased airborne transmission ability in ferrets. Our results suggested that canine may serve as an intermediate for the adaptation of avian influenza virus to human. Continuous surveillance coordinated with risk assessment for CIVs is necessary.

microbiology↗

bioRxiv2022

Integrated single-cell sequencing analysis reveals peripheral immune landscape across the human lifespan

Systematic understanding of immune dynamics across the entire human lifespan at single-cell resolution is currently lacking. Here, we performed single-cell RNA sequencing (scRNA-seq) and single-cell T cell receptor (TCR)/B cell receptor (BCR) sequencing (scTCR/BCR-seq) on over 380,000 peripheral blood mononuclear cells collected from 45 healthy participants aged 0 to over 90 years. We revealed that the functions of T cell subsets were most susceptible to senescence among all PBMCs, featured by increased NF-{kappa}B signaling and IFN-{gamma} responses pathways, while reduced telomere maintenance and energy metabolism. We subsequently explored the rewiring of cell-cell interactions among different immune cells across the lifespan and revealed the major alteration of immune checkpoints in T cells within the cellular interaction networks. By combined analysis of scRNA-seq and scTCR-seq, we revealed that 1) GNLY+ CD8 Effector T cells exhibited a high clonal expansion with distinct functional signatures in children and the elderly; 2) Naive CD4+ T and naive CD8+ T cells displayed different aging patterns in both transcriptomes and immune repertoires; and 3) CD8+ MAIT cells showed a higher cell abundance and clonal diversity in adolescents. Furthermore, we identified a unique cytotoxic B cell subset enriched in children by scRNA-seq and scBCR-seq analysis and experimental validations. In summary, our work provided valuable insights and rich resources for understanding the development and aging of the human immune system across the lifespan.

immunology↗

bioRxiv2022

Ubiquitin-based pathway acts inside chloroplasts to regulate photosynthesis

Photosynthesis is the energetic basis for most life on Earth, and in plants it operates inside double-membrane-bound organelles called chloroplasts. The photosynthetic apparatus comprises numerous proteins encoded by the nuclear and organellar genomes. Maintenance of this apparatus requires the action of internal chloroplast proteases, but a role for the nucleocytosolic ubiquitin-proteasome system (UPS) was not expected owing to the barrier presented by the double-membrane envelope. Here, we show that photosynthesis proteins (including those encoded internally by chloroplast genes) are ubiquitinated, and processed via the CHLORAD pathway: they are degraded by the 26S proteasome following CDC48-dependent retrotranslocation to the cytosol. This demonstrates that the reach of the UPS extends to the interior of endosymbiotically-derived chloroplasts, where it acts to regulate one of the most fundamental processes of life. One Sentence SummaryThe ubiquitin-proteasome system targets proteins inside chloroplasts, including chloroplast-encoded photosynthesis subunits.

plant biology↗

bioRxiv2022

Hetero-oligomerization of TDP-43 carboxy-terminal fragments with cellular proteins contributes to proteotoxicity

Carboxy terminal fragments (CTFs) of TDP-43 contain an intrinsically disordered region (IDR) and form cytoplasmic condensates containing amyloid fibrils. Such condensates are toxic and associated with pathogenicity in amyotrophic lateral sclerosis. However, the molecular details of how the domain of TDP-43 CTFs leads to condensation and cytotoxicity remain elusive. Here, we show that truncated RNA/DNA-recognition motif (RRM) at the N-terminus of TDP-43 CTFs leads to the structural transition of the IDR, whereas the IDR itself of TDP-43 CTFs is difficult to assemble even if they are proximate intermolecularly. Hetero-oligomers of TDP-43 CTFs that have recruited other proteins are more toxic than homo-oligomers, implicating loss-of-function of the endogenous proteins by such oligomers is associated with cytotoxicity. Furthermore, such toxicity of TDP-43 CTFs was cell-nonautonomously affected in the nematodes. Therefore, misfolding and oligomeric characteristics of the truncated RRM at the N-terminus of TDP-43 CTFs define their condensation properties and toxicity.

molecular biology↗

bioRxiv2022

MuSiC2: cell type deconvolution for multi-condition bulk RNA-seq data

Cell type composition of intact bulk tissues can vary across samples. Deciphering cell type composition and its changes during disease progression is an important step towards understanding disease pathogenesis. To infer cell type composition, existing cell type deconvolution methods for bulk RNA-seq data often require matched single-cell RNA-seq (scRNA-seq) data, generated from samples with similar clinical conditions, as reference. However, due to the difficulty of obtaining scRNA-seq data in diseased samples, only limited scRNA-seq data in matched disease conditions are available. Using scRNA-seq reference to deconvolve bulk RNA-seq data from samples with different disease conditions may lead to biased estimation of cell type proportions. To overcome this limitation, we propose an iterative estimation procedure, MuSiC2, which is an extension of MuSiC [1], to perform deconvolution analysis of bulk RNA-seq data generated from samples with multiple clinical conditions where at least one condition is different from that of the scRNA-seq reference. Extensive benchmark evaluations indicated that MuSiC2 improved the accuracy of cell type proportion estimates of bulk RNA-seq samples under different conditions as compared to the traditional MuSiC [1] deconvolution. MuSiC2 was applied to two bulk RNA-seq datasets for deconvolution analysis, including one from human pancreatic islets and the other from human retina. We show that MuSiC2 improves current deconvolution methods and provides more accurate cell type proportion estimates when the bulk and single-cell reference differ in clinical conditions. We believe the condition-specific cell type composition estimates from MuSiC2 will facilitate downstream analysis and help identify cellular targets of human diseases.

genomics↗

bioRxiv2022

Ex vivo to in vivo model of malignant peripheral nerve sheath tumors for precision oncology

Malignant peripheral nerve sheath tumors (MPNST) are aggressive soft tissue sarcomas that often develop in patients with neurofibromatosis type 1 (NF1-MPNST), but can occur sporadically. Through a multi-institution collaboration, we have developed 13 NF1-associated MPNST patient-derived xenografts (PDX). Genomic analysis of the PDX-tumor pairs identified somatic mutations in NF1 (61%), SUZ12 (61%), EED (15%), and TP53 (15%), and chromosome 8 (Chr8) gain (77%), consistent with published data. Pre-clinical models that capture this molecular heterogeneity are needed to identify and prioritize effective drug candidates for clinical translation. Here, we describe the successful development of a medium-throughput ex vivo 3D microtissue model with several advantages over 2D cell line growth, which can be utilized to predict drug response in vivo. Herein, we present proof-of-principle of this PDX-to-microtissue system, using four genomically representative MPNST and three drugs. This work highlights the development of a novel ex vivo to in vivo preclinical platform in MPNST that successfully captures the genomic diversity observed in patients and represents a resource to identify future therapeutic strategies.

cancer biology↗

bioRxiv2022

Melanosomes degrade lipofuscin and precursors that are derived from photoreceptor membrane turnover in the retinal pigment epithelium--an explanation for the origin of the melanolipofuscin granule

The accumulation of the age pigment lipofuscin within the retinal pigment epithelium (RPE) is one the most remarkable changes observed in association with age-related macular degeneration (AMD) and Stargardt disease. Both aging and pathological processes lead to the accumulation of melanolipofuscin (MLF) granules, which have been reported to reflect the onset of AMD more accurately than lipofuscin. The underlying mechanism by which MLF forms is still not understood. We investigate the potential role that melanin plays in the degradation of lipofuscin and MLF in pigmented Abca4-/- mice following treatment with several NO generating drugs. Abca4-/- mice are generally used as models for lipofuscin-related eye diseases. We also induced melanogenesis in albino Abca4-/- mice via the over-expression of tyrosinase, the key enzyme involved in melanogenesis. We compared the ultrastructure of lipofuscinogensis in the RPE of pigmented and albino Abca4-/- mice. Fluorescence microscopy was employed for the quantification of lipofuscin. We found high amounts of unique thin (3-4 nm) lamellar membranes (TLMs) that were left over from the degradation of photoreceptor disc membranes by high-resolution electron microscopy. Accumulated TLMs were significantly more frequent in the RPE cells of the albinos than the pigmented mice, indicating that melanin plays a role in removing TLMs. The intravitreal injection of several NO generating drugs was found to reduce the amount of autofluorescent lipofuscin in the cytoplasm of RPE cells, particularly the MLF granules of pigmented Abca4-/- mice. No effect was observed in terms of lipofuscin removal in NO-exposed albino Abca4-/- mice. However, transfection with tyrosinase led to a reduction in the lipofuscin levels of artificially pigmented RPE cells in albino Abca4-/- mice following the formation of melanin. The results show for the first time that melanin plays an important, if not a key, role in the degradation of lipofuscin in RPE cells.

neuroscience↗

bioRxiv2021

SHERRY2: A method for rapid and sensitive single cell RNA-seq

Prevalent single cell transcriptomic profiling (scRNA-seq) mechods are mainly based on synthesis and enrichment of full-length double-stranded complementary DNA. These approaches are challenging to generate accurate quantification of transcripts when their abundance is low or their full-length amplifications are difficult. Based on our previous finding that Tn5 transposase can directly cut-and-tag DNA/RNA hetero-duplexes, we present SHERRY2, a specifically optimized protocol for scRNA-seq without second strand cDNA synthesis. SHERRY2 is free of pre-amplification and eliminates the sequence-dependent bias. In comparison with other widely-used scRNA-seq methods, SHERRY2 exhibits significantly higher sensitivity and accuracy even for single nuclei. Besides, SHERRY2 is simple and robust, and can be easily scaled up to high-throughput experiments. When testing single lymphocytes and neuron nuclei, SHERRY2 not only obtained accurate countings of transcription factors and long non-coding RNAs, but also provided bias-free results that enriched genes in specific cellular components or functions, which outperformed other protocols. With a few thousand cells sequenced by SHERRY2, we confirmed expression and dynamics of Myc in different cell types of germinal centers, which were previously only revealed by gene-specific amplification methods. SHERRY2 is able to provide high sensitivity, high accuracy, and high throughput for those applications that require high number of genes identified in each cell. It can reveal the subtle transcriptomic difference between cells and facilitate important biological discoveries.

genomics↗

bioRxiv2021

Trial-by-trial fluctuations in amygdala activity track motivational enhancement of desirable sensory evidence during perceptual decision-making

People are biased towards seeing outcomes that they are motivated to see. For example, sports fans often perceive the same ambiguous foul in favor of the team they support. Here, we test the hypothesis that motivational biases in perceptual decision-making arise from amygdala-dependent biases in sensory processing. Human participants were rewarded for correctly categorizing an ambiguous image into one of two categories while undergoing fMRI. On each trial, we used a financial bonus to motivate participants to see one category over another. The reward maximizing strategy was to perform the categorizations accurately, but participants were biased towards categorizing the images as the category we motivated them to see. Heightened amygdala activity was associated with motivation consistent categorizations, and tracked trial-by-trial enhancement of neural activity in sensory cortices that was specific to the desirable category. Analyses using a drift diffusion model provide converging evidence that trial-by-trial amygdala activity was associated with stronger biases in the accumulation of sensory evidence. Prior work examining biases in perceptual decision-making have focused on the role of frontoparietal regions. Our work highlights an important contribution of the amygdala. When people are motivated to see one outcome over another, the amygdala biases perceptual decisions towards those outcomes.

neuroscience↗