Biology subjects

Kulkarni, A.

Publications and source records attributed to Kulkarni, A..

At least 73 records · Page 4Linked to original sources

bioRxiv2021

Acoustic Force Spectroscopy Reveals Subtle Differences in Cellulose Unbinding Behavior of Carbohydrate-Binding Modules

To rationally engineer more efficient cellulolytic enzymes for cellulosic biomass deconstruction into sugars for biofuels production, it is necessary to better understand the complex enzyme-substrate interfacial interactions. Carbohydrate binding modules (CBM) are often associated with microbial surface-tethered cellulosomal or freely secreted cellulase enzymes to increase substrate accessibility. However, it is not well known how CBM recognize, bind, and dissociate from polysaccharide surfaces to facilitate efficient cellulolytic activity due to the lack of mechanistic understanding of CBM-substrate interactions. Our work outlines a general approach to methodically study the unbinding behavior of CBMs from model polysaccharide surfaces using single-molecule force spectroscopy. Here, we apply acoustic force spectroscopy (AFS) to probe a Clostridium thermocellum cellulosomal scaffoldin protein (CBM3a) and measure its dissociation from nanocellulose surfaces at physiologically relevant, low force loading rates. An automated microfluidic setup and methodology for uniform deposition of insoluble polysaccharides on the AFS chip surfaces is demonstrated. The rupture forces of wild-type CBM3a, and its Y67A mutant, unbinding from nanocellulose surface suggests distinct CBM binding conformations that can also explain the improved cellulolytic activity of cellulase tethered to CBM. Applying established dynamic force spectroscopy theory, the single-molecule unbinding rate at zero force is extrapolated and found to agree well with bulk equilibrium unbinding rates estimated independently using quartz crystal microbalance with dissipation monitoring. However, our results highlight the limitations of applying classical theory to explain the highly multivalent CBM-cellulose interactions seen at higher cellulose-CBM bond rupture forces (>15pN). Significance StatementCellulases are multi-modular enzymes produced by numerous microbes that catalyze cellulose hydrolysis into glucose. These enzymes play an important role in global carbon cycling as well as cellulosic biofuels production. CBMs are essential components of cellulolytic enzymes involved in facilitating hydrolysis of polysaccharides by tethered catalytic domains (CD). The subtle interplay between CBM binding and CD activity is poorly understood particularly for heterogeneous reactions at solid-liquid interfaces. Here, we report a highly multiplexed single-molecule force spectroscopy method to study CBM dissociation from cellulose to infer the molecular mechanism governing substrate recognition and dissociation. This approach can be broadly applied to study multivalent protein-polysaccharide binding interactions relevant to other carbohydrates such as starch, chitin, or hyaluronan to engineer efficient biocatalysts.

biochemistry↗

bioRxiv2021

Using Deep Learning to Count Monarch Butterflies in Dense Clusters

Monarch butterflies display one of the most fascinating migration patterns of all species, traveling over 3000 miles from their North American breeding grounds to reach overwintering sites in Central Mexico. Recent studies have suggested that monarchs have experienced an alarming decline in population size due to a combination of deforestation, loss of native milkweed and nectaring plants, and climate change. An issue that conservation efforts face is the lack of principled mechanisms to accurately estimate and count the population size of monarchs. This difficulty occurs due to their small size and existence in dense overwintering clusters in forests. We create an open-source tool to aid conservationists estimate the count of monarch butterflies from images automatically. To the best of our knowledge, our approach, based on deep convolutional neural networks, is the first automated application that can count small insects like monarch butterflies in dense clusters. We demonstrate that our approach achieves high accuracy in counting the number of butterflies even in the presence of occlusion. We also release an open-source dataset containing high resolution images of monarch butterflies along with human annotations for each butterflys position. Our open-source implementation can be readily used by scientists to estimate monarch numbers in overwintering clusters and could also be adapted for use in other clustering species.

bioengineering↗

bioRxiv2021

Gain-of-function cardiomyopathic mutations in RBM20 rewire splicing regulation and re-distribute ribonucleoprotein aggregates within processing bodies

RNA binding motif protein 20 (RBM20) is a key regulator of alternative splicing in the heart, and its mutation leads to malignant dilated cardiomyopathy (DCM). To understand the mechanism of RBM20-associated DCM, we engineered isogenic human induced pluripotent stem cells (iPSCs) with heterozygous or homozygous DCM-associated missense mutations in RBM20 (R636S) as well as RBM20 knockout (KO) iPSCs. iPSC-derived engineered heart tissues made from these cell lines recapitulated contractile dysfunction of RBM20-associated DCM and revealed greater dysfunction with missense mutations than KO. Analysis of RBM20 RNA binding by eCLIP revealed a gain-of-function preference of mutant RBM20 for 3' UTR sequences that are shared with amyotrophic lateral sclerosis (ALS) and processing-body associated RNA binding proteins (FUS, DDX6). Deep RNA sequencing revealed that the RBM20 R636S mutant has unique gene, splicing, polyadenylation and circular RNA defects that differ from RBM20 KO, impacting distinct cardiac signaling pathways. Splicing defects specific to KO or R636S mutations were supported by data from R636S gene-edited pig hearts and eCLIP. Super-resolution microscopy verified that mutant RBM20 maintains limited nuclear localization potential; rather, the mutant protein associates with cytoplasmic processing bodies (DDX6) under basal conditions, and with stress granules (G3BP1) following acute stress. Taken together, our results highlight a novel pathogenic mechanism in cardiac disease through splicing-dependent and -independent pathways that are likely to mediate differential contractile phenotypes and stress-associated heart pathology.

cell biology↗

bioRxiv2021

Multiple Sites on SARS-CoV-2 Spike Protein are Susceptible to Proteolysis by Cathepsins B, K, L, S, and V

SARS-CoV-2 is the coronavirus responsible for the COVID-19 pandemic. Proteases are central to the infection process of SARS-CoV-2. Cleavage of the spike protein on the viruss capsid causes the conformational change that leads to membrane fusion and viral entry into the target cell. Since inhibition of one protease, even the dominant protease like TMPRSS2, may not be sufficient to block SARS-CoV-2 entry into cells, other proteases that may play an activating role and hydrolyze the spike protein must be identified. We identified amino acid sequences in all regions of spike protein, including the S1/S2 region critical for activation and viral entry, that are susceptible to cleavage by furin and cathepsins B, K, L, S, and V using PACMANS, a computational platform that identifies and ranks preferred sites of proteolytic cleavage on substrates, and verified with molecular docking analysis and immunoblotting to determine if binding of these proteases can occur on the spike protein that were identified as possible cleavage sites. Together, this study highlights cathepsins B, K, L, S, and V for consideration in SARS-CoV-2 infection and presents methodologies by which other proteases can be screened to determine a role in viral entry. This highlights additional proteases to be considered in COVID-19 studies, particularly regarding exacerbated damage in inflammatory preconditions where these proteases are generally upregulated.

bioengineering↗

bioRxiv2021

12-Lipoxygenase Governs the Innate Immune Pathogenesis of Islet Inflammation and Autoimmune Diabetes

Macrophages and related myeloid cells are innate immune cells that participate in the early islet inflammation of type 1 diabetes (T1D). The inflammatory signals and antigen presentation by these cells may be inducers of the adaptive immune response that is the hallmark of T1D. The enzyme 12-lipoxygenase (12-LOX) catalyzes the formation of pro-inflammatory eicosanoids from membrane-derived phospholipids, but its role and mechanisms in the pathogenesis of islet inflammation have not been elucidated. Leveraging a model of T1D-like islet inflammation in zebrafish, we show here that macrophages contribute significantly to the loss of {beta}-cells and the subsequent development of hyperglycemia. Depletion or inhibition of 12-LOX in this model resulted in significantly reduced macrophage infiltration into islets with preservation of {beta}-cell mass. In mice, we deleted the gene encoding 12-LOX (Alox15) in the myeloid lineage in the non-obese diabetic (NOD) model of T1D. Myeloid cell-specific Alox15 knockout NOD mice demonstrated reduced insulitis and T-cell responses, preserved {beta} cell mass, and almost complete protection from the development of T1D. A critical effect of 12-LOX depletion appeared secondary to a defect in myeloid cell migration, a function required for immune surveillance and tissue injury responses. This effect on migration appeared to be secondary to the loss of the chemokine receptor CXCR3. Transgenic expression of the gene encoding CXCR3 rescued the migrator defect in zebrafish 12-LOX morphants. Taken together, our results reveal a formative role for innate immune myeloid cells in the early pathogenesis of T1D and identify 12-LOX as a necessary enzyme to promote their pro-diabetogenic phenotype in the context of autoimmunity.

immunology↗

bioRxiv2020

Transcription factors Aryl hydrocarbon receptor and TGF-inducible early gene are involved in an axis modulating immune response in mosquitoes

Immune homeostasis ensures effective pathogen defense and avoids overactivity, which is achieved through an orchestrated transcriptional network. Here we demonstrate that mosquito AhR and TIEG mediate a transcriptional axis to modulate the immune response. The AhR agonist compromised the immunity with reduced survival upon the challenge with bacterium Serratia fonticola, while the AhR antagonists enhanced the immunity with increased survival. The phenotype of pharmacological immune enhancement was corroborated genetically by the AhR gene silencing. The transcriptome comparison following AhR manipulations highlighted a set of AhR regulated genes, from which transcription factor TIEG, the ortholog of Kruppel-like factor 10, was chosen for further study. TIEG was required for the AhR mediated immune modulation. Silencing TIEG increased survival and reversed the immune suppression mediated by agonist-activated AhR. Among the transcriptomes, there were genes sharing co-expression patterns in the cohorts with AhR manipulation pharmacologically or genetically. Moreover, the mosquitoes with silenced TIEG and AhR shared ~68% altered genes upon infection. Together, the data suggest TIEG is downstream of AhR, acting as a major transcription factor mediating the immune modulation. The TIEG targets include genes involved in sugar metabolism and circadian rhythms, both processes are critical for immune homeostasis. In the naive mosquitoes, the AhR-TIEG axis prevents the adverse effect of the overactivated IMD pathway created by silencing the inhibitor Caspar. In summary, AhR and TIEG constitute a transcriptional axis that mediates a gene network critical for maintaining immune homeostasis. SignificanceImmune homeostasis is sustained by various parameters involving different transcriptional regulatory networks. Such knowledge in mosquitoes remains scarce. Here, using AhR manipulation and transcriptome interrogation, we demonstrate that AhR and TIEG (a KLF10 ortholog) constitute a transcriptional axis to mediate immune modulation using an antibacterial immune model in the malaria vector Anopheles gambiae. AhR is a ligand-activated transcription factor that senses environmental signals and transcribes relevant genes to modulate immune responses. TIEG/KLF10, conserved from invertebrates to mammals, mediates various transcriptional networks. Our data show that the AhR-TIEG axis controls the genes involving in sugar sensing and circadian rhythms in the infection context. This finding warrants further study to elucidate the transcriptional control of metabolic and circadian behind immune homeostasis.

immunology↗

bioRxiv2020

Adaptation of codon and amino acid use for translational functions in highly expressed cricket genes

BackgroundFor multicellular organisms, much remains unknown about the dynamics of synonymous codon and amino acid use in highly expressed genes, including whether their use varies with expression in different tissue types and sexes. Moreover, specific codons and amino acids may have translational functions in highly transcribed genes, that largely depend on their relationships to tRNA gene copies in the genome. However, these relationships and putative functions are poorly understood, particularly in multicellular systems. ResultsHere, we rigorously studied codon and amino acid use in highly expressed genes from reproductive and nervous system tissues (male and female gonad, somatic reproductive system, brain, ventral nerve cord, and male accessory glands) in the cricket Gryllus bimaculatus. We report an optimal codon, defined as the codon preferentially used in highly expressed genes, for each of the 18 amino acids with synonymous codons in this organism. The optimal codons were largely shaped by selection, and their identities were mostly shared among tissue types and both sexes. However, the frequency of optimal codons was highest in gonadal genes. Concordant with translational selection, a majority of the optimal codons had abundant matching tRNA gene copies in the genome, but sometimes obligately required wobble tRNAs. We suggest the latter may comprise a mechanism for slowing translation of abundant transcripts, particularly for cell-cycle genes. Non-optimal codons, defined as those least commonly used in highly transcribed genes, intriguingly often had abundant tRNAs, and had elevated use in a subset of genes with specialized functions (gametic and apoptosis genes), suggesting their use promotes the upregulation of particular mRNAs. In terms of amino acids, we found evidence suggesting that amino acid frequency, tRNA gene copy number, and amino acid biosynthetic costs (size/complexity) had all interdependently evolved in this insect model, potentially for translational optimization. ConclusionsCollectively, the results strongly suggest that codon use in highly expressed genes, including optimal, wobble, and non-optimal codons, and their tRNAs abundances, as well as amino acid use, have been adapted for various functional roles in translation within this cricket. The effects of expression in different tissue types and the two sexes are discussed.

genomics↗

bioRxiv2020

Expression of Tim-3 drives naive Treg to an effector-like state with enhanced suppressive activity

Regulatory T cells (Treg) are critical mediators of self-tolerance but can also limit effective anti-tumor immunity. We and others previously reported that 40-60% percent of Treg-infiltrating head and neck cancer (HNC) and other tumors highly express Tim-3, compared with about 5% in lymphoid organs. Tumor-infiltrating Tim-3+ Treg also have enhanced suppressive function and display a more effector-like phenotype. Using a novel mouse model with cell type-specific Tim-3 expression, we show here that expression of Tim-3 by Treg is sufficient to drive Treg to a more effector-like phenotype, resulting in enhanced suppressive activity and increased tumor growth. These findings may help to reconcile previous reports that some Tim-3 antibodies enhance T cell responses in vivo, while expression of Tim-3 has a cell-intrinsic ability to enhance TCR signaling and T cell activation. Thus, we propose that Tim-3 regulates anti-tumor immunity at least in part through enhancement of Treg function. To our knowledge, this is the first example in which expression of a single co-stimulatory molecule is sufficient to drive differentiation of Treg in this manner.

immunology↗

bioRxiv2020

FOXP1 negatively regulates intrinsic excitability in D2 striatal projection neurons by promoting inwardly rectifying and leak potassium currents

Heterozygous loss-of-function mutations in the transcription factor FOXP1 are strongly associated with autism. Dopamine receptor 2 expressing (D2) striatal projection neurons (SPNs) in heterozygous Foxp1 (Foxp1+/-) mice have higher intrinsic excitability. To understand the mechanisms underlying this alteration, we examined SPNs with cell-type specific homozygous Foxp1 deletion to study cell-autonomous regulation by Foxp1. As in Foxp1+/- mice, D2 SPNs had increased intrinsic excitability with homozygous Foxp1 deletion. This effect involved postnatal mechanisms. The hyperexcitability was mainly due to down-regulation of two classes of potassium currents: inwardly rectifying (KIR) and leak (KLeak). Single-cell RNA sequencing data from D2 SPNs with Foxp1 deletion indicated the down-regulation of transcripts of candidate ion channels that may underlie these currents: Kcnj2 and Kcnj4 for KIR and Kcnk2 for KLeak. This Foxp1-dependent regulation was neuron-type specific since these same currents and transcripts were either unchanged, or very little changed, in D1 SPNs with cell-specific Foxp1 deletion. Our data are consistent with a model where FOXP1 negatively regulates the excitability of D2 SPNs through KIR and KLeak by transcriptionally activating their corresponding transcripts. This, in turn, provides a novel example of how a transcription factor may regulate multiple genes to impact neuronal electrophysiological function that depends on the integration of multiple current types - and do this in a cell-specific fashion. Our findings provide initial clues to altered neuronal function and possible therapeutic strategies not only for FOXP1-associated autism but also for other autism forms associated with transcription factor dysfunction.

neuroscience↗

bioRxiv2020

Sex-biased genes expressed in the cricket brain evolve rapidly

Sex-biased gene expression, particularly sex-biased expression in the gonad, has been linked to rates of protein sequence evolution (nonsynonymous to synonymous substitutions, dN/dS) in animals. However, in insects, sex-biased expression studies remain centered on a few holometabolous species, and moreover, other major tissue types such as the brain remain underexplored. Here, we studied sex-biased gene expression and protein evolution in a hemimetabolous insect, the cricket Gryllus bimaculatus. We generated novel male and female RNA-seq data for two sexual tissue types, the gonad and somatic reproductive system, and for two core components of the nervous system, the brain and ventral nerve cord. From a genome-wide analysis, we report several core findings. Firstly, testis-biased genes had accelerated evolution, as compared to ovary-biased and unbiased genes, which was associated with positive selection events. Secondly, while sex-biased brain genes were much less common than for the gonad, they exhibited a striking tendency for rapid protein evolution, an effect that was stronger for the female than male brain. Further, some sex-biased brain genes were linked to sexual functions and mating behaviors, which we suggest may have accelerated their evolution via sexual selection. Thirdly, a tendency for narrow cross-tissue expression breadth, suggesting low pleiotropy, was observed for sex-biased brain genes, suggesting relaxed purifying selection, which we speculate may allow enhanced freedom to evolve adaptive protein functional changes. The findings of rapid evolution of testis-biased genes and male and female-biased brain genes are discussed with respect to pleiotropy, positive selection, and the mating biology of this cricket.

evolutionary biology↗

bioRxiv2020

Synchronization, stochasticity and phase waves in neuronal networks with spatially-structured connectivity

Oscillations in the beta/low gamma range (10-45 Hz) are recorded in diverse neural structures. They have successfully been modeled as sparsely synchronized oscillations arising from reciprocal interactions between randomly connected excitatory (E) pyramidal cells and local interneurons (I). The synchronization of spatially distant oscillatory spiking E-I modules has been well studied in the rate model framework but less so for modules of spiking neurons. Here, we first show that previously proposed modifications of rate models provide a quantitative description of spiking E-I modules of Exponential Integrate-and-Fire (EIF) neurons. This allows us to analyze the dynamical regimes of sparsely synchronized oscillatory E-I modules connected by long-range excitatory interactions, for two modules, as well as for a chain of such modules. For modules with a large number of neurons (> 105), we obtain results similar to previously obtained ones based on the classic deterministic Wilson-Cowan rate model, with the added bonus that the results quantitatively describe simulations of spiking EIF neurons. However, for modules with a moderate (~ 104) number of neurons, stochastic variations in the spike emission of neurons are important and need to be taken into account. On the one hand, they modify the oscillations in a way that tends to promote synchronization between different modules. On the other hand, independent fluctuations on different modules tend to disrupt synchronization. The correlations between distant oscillatory modules can be described by stochastic equations for the oscillator phases that have been intensely studied in other contexts. On shorter distances, we develop a description that also takes into account amplitude modes and that quantitatively accounts for our simulation data. Stochastic dephasing of neighboring modules produces transient phase gradients and the transient appearance of phase waves. We propose that these stochastically-induced phase waves provide an explanative framework for the observations of traveling waves in the cortex during beta oscillations.

neuroscience↗

bioRxiv2020

An essential role for MEF2C in the cortical response to loss of sleep

Neuronal activity and gene expression in response to the loss of sleep can provide a window into the enigma of sleep function. Sleep loss is associated with brain differential gene expression, an increase in pyramidal cell mEPSC frequency and amplitude, and a characteristic rebound and resolution of slow wave sleep-slow wave activity (SWS-SWA). However, the molecular mechanism(s) mediating the sleep loss response are not well understood. We show that sleep-loss regulates MEF2C phosphorylation, a key mechanism regulating MEF2C transcriptional activity, and that MEF2C function in postnatal excitatory forebrain neurons is required for the biological events in response to sleep loss. These include altered gene expression, the increase and recovery of synaptic strength, and the rebound and resolution of SWS-SWA, which implicate MEF2C as an essential regulator of sleep function. One Sentence SummaryMEF2C is critical to the response to sleep loss.

neuroscience↗

bioRxiv2020

Subthreshold repertoire and threshold dynamics of midbrain dopamine neuron firing in vivo.

The firing pattern of ventral midbrain dopamine neurons is controlled by afferent and intrinsic activity to generate prediction error signals that are essential for reward-based learning. Given the absence of intracellular in vivo recordings in the last three decades, the subthreshold membrane potential events that cause changes in dopamine neuron firing patterns remain unknown. By establishing stable in vivo whole-cell recordings of >100 spontaneously active midbrain dopamine neurons in anaesthetized mice, we identified the repertoire of subthreshold membrane potential signatures associated with distinct in vivo firing patterns. We demonstrate that dopamine neuron in vivo activity deviates from a single spike pacemaker pattern by eliciting transient increases in firing rate generated by at least two diametrically opposing biophysical mechanisms: a transient depolarization resulting in high frequency plateau bursts associated with a reactive, depolarizing shift in action potential threshold; and a prolonged hyperpolarization preceding slower rebound bursts characterized by a predictive, hyperpolarizing shift in action potential threshold. Our findings therefore illustrate a framework for the biophysical implementation of prediction error and sensory cue coding in dopamine neurons by tuning action potential threshold dynamics.

neuroscience↗

bioRxiv2020

Functional Identification of Specialized Basal Ganglia Circuits that Regulate Vocal Motor Sequences

Disruption of the transcription factor FoxP2, which is enriched in the basal ganglia, impair vocal development in humans and songbirds. The basal ganglia are essential for the selection and sequencing of motor actions, but the circuit mechanisms governing accurate sequencing of learned vocalizations are unknown. Here, we show expression of FoxP2 in the basal ganglia is vital for the fluent initiation and termination of birdsong, and the maintenance of song syllable sequencing in adulthood. Knockdown of FoxP2 imbalances dopamine receptor expression across striatal direct-like and indirect-like pathways, suggesting a role of dopaminergic signaling in regulating vocal-motor sequencing. Confirming this prediction, we show that phasic dopamine activation, and not inhibition, during singing drives repetition of song syllables, thus also impairing fluent initiation and termination of birdsong. These findings demonstrate discrete circuit origins for the dysfluent repetition of vocal elements, a phenotype commonly observed in speech disorders.

neuroscience↗

bioRxiv2020

Disparities in information on Long-Acting Reversible Contraceptives available to college students on student health center websites in USA

Long Acting Reversible Contraceptive (LARC) methods are among the most effective birth control approaches for adolescent and young adults yet information on these methods is not widespread. We examine LARC information provided by Student Health Centers (SHC) websites from Universities across the USA to document disparities in access to information on these important contraception methods for college students. We find that compared to EC, Condoms, (plus Pap smear as control), LARC is mentioned less frequently than the others and 73% of schools have no LARC content on their SHC websites. There is no standardization in how the sexual and reproductive health information is organized on SHC websites, which might hinder access. When LARC information does exist, readability and accessibility vary. Universities having high rates of the student body who are African American or female are less likely to provide LARC information on their SHC website and universities situated in more rural settings are less likely to post LARC information on their websites.

scientific communication and education↗

bioRxiv2019

Highly diverse Asgard archaea participate in organic matter degradation in coastal sediments

Asgard is an archaeal superphylum that might hold the key to understand the origin of eukaryotes, but its diversity and ecological roles remain poorly understood. Here, we reconstructed 15 metagenomic-assembled genomes (MAGs) from coastal sediments covering most known Asgard archaea and a novel group, which is proposed as a new Asgard phylum named as the "Gerdarchaeota". Genomic analyses predict that Gerdarchaeota are facultative anaerobes in utilizing both organic and inorganic carbon. Unlike their closest relatives Heimdallarchaeota, Gerdarchaeota have genes encoding for cellulase and enzymes involving in the tetrahydromethanopterin-based Wood-Ljungdahl pathway. Transcriptomic evidence showed that all known Asgard archaea are capable of degrading organic matter, including peptides, amino acids and fatty acids, in different ecological niches in sediments. Overall, this study broadens the diversity of the mysterious Asgard archaea and provides evidence for their ecological roles in coastal sediments.

microbiology↗

bioRxiv2019

A simple device to immobilize protists for electrophysiology and microinjection

We present a simple device to mechanically immobilize motile cells such as ciliates and flagellates. It can be used in particular for intracellular electrophysiology and microinjection. A transparent filter with holes smaller than the specimen is stretched over an outlet. A flow is induced by either a peristaltic pump or a depressurized tank, mechanically entraining cells to the bottom, where they immobilize against the filter. The cells swim again freely as soon as the flow is stopped. We demonstrate the device by recording action potentials in Paramecium and injecting a fluorescent dye in the cytosol.

microbiology↗

bioRxiv2019

The genomic underpinnings of oscillatory biomarkers supporting successful memory encoding in humans

In humans, brain oscillations are thought to support critical features of memory formation such as coordination of activity across regions, consolidation, and temporal ordering of events. However, understanding the molecular mechanisms underlining this activity in humans remains a major challenge. Here, we measured memory-sensitive oscillations using direct intracranial electroencephalography recordings from the temporal cortex of patients performing an episodic memory task. By then employing transcriptomics on the resected tissue from the same patients, we linked gene expression with brain oscillations, identifying genes correlated with oscillatory signatures of memory formation across six frequency bands. A co-expression analysis isolated biomarker-specific modules associated with neuropsychiatric disorders as well as ion channel activity. Using single-nuclei transcriptomic data from this resected tissue, we further revealed that biomarker-specific modules are enriched for both excitatory and inhibitory neurons. This unprecedented dataset of patient-specific brain oscillations coupled to genomics unlocks new insights into the genetic mechanisms that support memory encoding. By linking brain expression of these genes to oscillatory patterns, our data help overcome limitations of phenotypic methods to uncover genetic links to memory performance.

genomics↗