Biology subjects

Song, Y.

Publications and source records attributed to Song, Y..

At least 181 records · Page 10Linked to original sources

bioRxiv2024

Tracing neurodiverse disruptions underlying emotional episodic memory to diagnosis-specific network of emotional regulation in psychiatric disorders

BackgroundAffective symptoms are a prevalent psychopathological feature in various psychiatric disorders. However, the underlying neurobiological mechanisms are complex and not yet fully understood. MethodsWe used normative modelling to establish a reference for neurofunctional activation of functional magnetic resonance imaging based on an emotional episodic memory task, which is frequently used to study affective symptoms in psychiatric disorders. This normative reference was derived from a large dataset of healthy individuals (n = 409), and used to evaluate individualized functional alterations by calculating deviations from this reference in a clinical dataset of 328 participants, which included 168 healthy controls and patients with major depressive disorder (MDD, n = 56), bipolar disorder (BD, n = 31), and schizophrenia (SZ, n = 73). The neurofunctional deviations were mapped to emotional networks with specific emotional functions and used to predict affective symptoms in different mental disorders. The microscale cellular signatures underlying macroscale variations were identified using imaging transcriptomic analysis, and associated with affective symptoms. ResultsWe observed distinct patterns of cross-scale neural alterations linked to affective symptoms in three psychiatric disorders. Macroscale neural dysfunctions in distinct disorders were embedded into non-overlapping emotional networks and significantly associated with affective symptoms. The oligodendrocytes may mediate the network-specific impairments, and microglia for MDD, astrocytes for BD, and excitatory neurons for SZ as replicable cell-type correlates of affective symptoms. ConclusionsThese findings have potential implications for the understanding of unique neuropathological patterns of affective symptoms in distinct psychiatric disorders and improving individualized treatment response.

neuroscience↗

bioRxiv2024

Evolution of iGluR ligand specificity, polyamine regulation, and ion selectivity inferred from a placozoan Epsilon receptor

Epsilon ionotropic glutamate receptors (iGluRs) belong to a recently described sub-family of metazoan receptors that is distinct from the AMPA, Kainate, Delta, and Phi (i.e., AKDF) sub-family, the NMDA sub-family, and the Lambda subfamily. Here, we sought to better understand the evolutionary and functional properties of Epsilon receptors by focusing on homologues from the basal invertebrate Trichoplax adhaerens (phylum Placozoa). We provide an updated species-guided phylogeny of eukaryotic iGluRs, and a comprehensive phylogeny of placozoan receptors uncovering marked diversification of Epsilon receptors within three conserved subclades, and four invariable subclades of AKDF receptors. Detailed functional characterization of the T. adhaerens Epsilon receptor GluE1A revealed robust activation by glycine, alanine, serine, and valine, but not glutamate. Through combined of structural modeling and mutation experiments, we used GluE1A to test the hypothesis that only a small set of amino acids in the ligand binding domain determine ligand selectivity. Mutation of just three amino acids converted GluE1A selectivity to glutamate, resulted in nascent sensitivity to AMPA, and increased sensitivity to the AMPA/Kainate receptor blocker CNQX. Lastly, combined modeling and mutation experiments revealed that an atypical serine residue in the pore NQR site of GluE1A, along with an aspartate four amino acids downstream, confers sensitivity to voltage-dependent polyamine block, while the serine alone diminishes both polyamine block and Ca2+ permeation compared to asparagine and glutamine residues of AMPA and Kainate receptors. Altogether, we demonstrate conserved molecular determinants for polyamine regulation between Epsilon and AKDF receptors, and evidence that natural variations in NQR residues have important implications for ion permeation and regulation by polyamines.

neuroscience↗

bioRxiv2024

Context-aware comparison of cell type gene expression across species

The cross-species comparison of expression profiles uncovers functional similarities and differences between cell types and helps refining their evolutionary relationships. Current analysis strategies typically follow the ortholog conjecture, which posits that the expression of orthologous genes is most similar between species. However, the extent to which this holds true at different evolutionary distances is unknown. Here, we systematically explore the ortholog conjecture in comparative scRNA-seq data. We devise a robust analytical framework, GeneSpectra, to classify genes by expression specificity and distribution across cell types. Our analysis reveals that genes expressed ubiquitously across nearly all cell types exhibit strong conservation of this pattern across species, as do genes with high expression specificity. In contrast, genes within intermediate specificity fluctuate between classes. As expected, ortholog expression becomes more divergent with increased species distance. We also find an overall correlation between similarity in expression profiles and sequence conservation. Finally, our results allow identifying gene classes with highest probability of expression pattern conservation that are most useful for cell type alignment between species. Calibrating reliance on the ortholog conjecture for individual genes, we thus provide a comprehensive framework for the comparative analysis of single cell data.

bioinformatics↗

bioRxiv2024

Metabolite T2 relaxation times decrease across the adult lifespan in a large multi-site cohort

PurposeRelaxation correction is crucial for accurately estimating metabolite concentrations measured using in vivo magnetic resonance spectroscopy (MRS). However, the majority of MRS quantification routines assume that relaxation values remain constant across the lifespan, despite prior evidence of T2 changes with aging for multiple of the major metabolites. Here, we comprehensively investigate correlations between T2 and age in a large, multi-site cohort. MethodsWe recruited approximately 10 male and 10 female participants from each decade of life: 18-29, 30-39, 40-49, 50-59, and 60+ years old (n=101 total). We collected PRESS data at 8 TEs (30, 50, 74, 101, 135, 179, 241, and 350 ms) from voxels placed in white-matter-rich centrum semiovale (CSO) and gray-matter-rich posterior cingulate cortex (PCC). We quantified metabolite amplitudes using Osprey and fit exponential decay curves to estimate T2. ResultsOlder age was correlated with shorter T2 for tNAA, tCr3.0, tCr3.9, tCho, Glx, and tissue water in CSO and PCC; rs = -0.21 to -0.65, all p<0.05, FDR-corrected for multiple comparisons. These associations remained statistically significant when controlling for cortical atrophy. T2 values did not differ across the adult lifespan for mI. By region, T2 values were longer in the CSO for tNAA, tCr3.0, tCr3.9, Glx, and tissue water and longer in the PCC for tCho and mI. ConclusionThese findings underscore the importance of considering metabolite T2 changes with aging in MRS quantification. We suggest that future 3T work utilize the equations presented here to estimate age-specific T2 values instead of relying on uniform default values.

neuroscience↗

bioRxiv2024

Molecular basis of Ad5-nCoV Vaccine-Induced Immunogenicity

In response to coronavirus disease 2019 (COVID-19), numerous vaccines have been developed to protect against SARS-CoV-2 infection. Ad5-nCoV (Convidecia) is a vaccine listed for emergency use by the WHO and has been administrated to millions of people globally. It comprises a series of human adenovirus 5 (Ad5) replication-incompetent vectored vaccines that transduce the spike protein (S) gene of various SARS-CoV-2 strains. Despite promising clinical data demonstrating its safety and effectiveness, the underlying molecular mechanism of its high immunogenicity and incidence of adverse reactions remains less understood. Here we combined cryo-ET, fluorescence microscopy and mass spectrometry to characterize the in situ structures, density and site-specific glycan compositions of the Ad5-nCoV_Wu and Ad5-nCoV_O vaccine-induced S antigens, which encode the unmodified SARS-CoV-2 Wuhan-Hu-1 S gene and optimized Omicron S gene, respectively. We found that the vaccine-induced S are structurally intact, antigenic and densely distributed on the cell membrane. Compared to Ad5-nCoV_Wu induced S, the Ad5-nCoV_O induced S demonstrate significantly better stability and is less likely to induce syncytia among inoculated cells. Our work demonstrated that Ad5-nCoV is a prominent platform for antigen induction and cryo-ET can be a useful technique for vaccine characterization and development.

biophysics↗

bioRxiv2024

H2A.Z deposition at meiotic prophase I underlies homologous recombination and pachytene genome activation during male meiosis

Accurate meiotic progression is important for gamete formation and the generation of genetic diversity. However, little is known about the identity of chromatin regulators that underlie mammalian meiosis in vivo. Here, we identify the multifaceted functions of the chromatin remodeler ZNHIT1 in governing meiosis. The expression of Znhit1 gradually increases during the meiotic prophase, and Znhit1 knockout in spermatocytes results in arrested pachytene development, impaired DNA double-strand break repair, and defective homologous recombination. Single-cell RNA sequencing and transcriptome analysis reveal that Znhit1 loss dysregulates meiotic transcriptional programs at the pachytene stage. Chromatin immunoprecipitation data show that ZNHIT1 is needed for the incorporation of the histone variant H2A.Z into pachytene chromatin. Moreover, we found that H2A.Z cooperates with the transcription factor A-MYB to co-bind DNA elements and control gene activity. Our findings provide insights into the regulatory mechanisms governing meiotic progression and highlight ZNHIT1 as a critical regulator of meiotic progression.

developmental biology↗

bioRxiv2024

Peptidergic neurons with extensive branching orchestrate the internal states and energy balance of male Drosophila melanogaster.

Neuropeptide SIFamide (SIFa) neurons in Drosophila melanogaster have been characterized by their exceptionally elaborate arborization patterns, which extend from the brain into the ventral nerve cord (VNC). SIFa neurons are equipped to receive signals that integrate both internal physiological cues and external environmental stimuli. These signals enable the neurons to regulate energy balance, sleep patterns, metabolic status, and circadian timing. These peptidergic neurons are instrumental in orchestrating the animals internal states and refining its behavioral responses, yet the precise molecular underpinnings of this process remain elusive. Here we demonstrate that SIFa neurons coordinate a range of behavioral responses by selectively integrating inputs and outputs in a context-dependent manner. These neurons engage in a feedback loop with sNPF neurons in the ventral nerve cord, modifying behaviors such as long mating duration (LMD) and shorter mating duration (SMD). Furthermore, SIFa neurons receive essential inputs from neuropeptides Dsk, sNPF, and dilp2, which regulate interval timing behaviors. Activating SIFa neurons leads to reduced mating duration and increased food intake, while deactivating them reduces food intake. Overall, these findings demonstrate the importance of SIFa neurons in absorbing inputs and turning them into behavioral outputs, shedding light on animals intricate behavioral orchestration.

neuroscience↗

bioRxiv2024

Long-range neuropeptide relay as a central-peripheral communication mechanism for the context-dependent modulation of interval timing behaviors.

Neuropeptides play crucial roles in regulating context-dependent behaviors, but the underlying mechanisms remain elusive. We investigate the role of the neuropeptide SIFa and its receptor SIFaR in regulating two distinct mating duration behaviors in male Drosophila: Longer-Mating-Duration (LMD) and Shorter-Mating-Duration (SMD). We found that SIFaR expression in specific neurons is required for both LMD and SMD behaviors. Social context and sexual experience lead to synaptic reorganization between SIFa and SIFaR neurons, altering internal states of brain. We revealed that the SIFa-SIFaR/Crz-CrzR neuropeptide relay pathway is essential for generating distinct interval timing behaviors, with Crz neurons being responsive to the activity of SIFa neurons. Additionally, CrzR expression in non-neuronal cells is critical for regulating LMD and SMD behaviors. Our study provides insights into how neuropeptides and their receptors modulate context-dependent behaviors through synaptic plasticity and calcium signaling, with implications for understanding the neural circuitry underlying interval timing and neuropeptidergic system modulation of behavioral adaptations.

neuroscience↗

bioRxiv2024

Biophysical mapping of TREM2-ligand interactions reveals shared surfaces for engagement of multiple AD ligands

TREM2 is a signaling receptor expressed on microglia that has emerged as an important potential drug target for Alzheimers disease and other neurodegenerative diseases. While a number of TREM2 signaling ligands have been identified, little is known regarding the structural details of how it engages them. To better understand this, we created a protein library of 28 different TREM2 variants and 11 different sTREM2 variants that could be used to map interactions with various ligands using biolayer interferometry (BLI). The variants are located in previously identified putative binding surfaces on TREM2 called the hydrophobic site, basic site, and site 2. We found that mutations to the hydrophobic site ablated binding to apoE4, oAb42, and TDP-43. Competition binding experiments further supported that apoE4 and oAb42 share overlapping binding sites on TREM2. In contrast, binding to IL-34 was mediated by the basic site at a surface centering on R76. Competition binding experiments validated a unique site for IL-34, showing little to no competition with either oAb42 or apoE4. Altogether, our results suggest that TREM2 utilizes the hydrophobic site (consisting of CDR1, CDR2, and CDR3) as a common site to engage multiple ligands, and further implies that pharmaceutical strategies targeting this surface might be effective to modulate TREM2 functions.

biophysics↗

bioRxiv2024

A single-cell atlas characterizes dysregulation of the bone marrow immune microenvironment associated with outcomes in multiple myeloma

Multiple Myeloma (MM) remains incurable despite advances in treatment options. Although tumor subtypes and specific DNA abnormalities are linked to worse prognosis, the impact of immune dysfunction on disease emergence and/or treatment sensitivity remains unclear. We established a harmonized consortium to generate an Immune Atlas of MM aimed at informing disease etiology, risk stratification, and potential therapeutic strategies. We generated a transcriptome profile of 1,149,344 single cells from the bone marrow of 263 newly diagnosed patients enrolled in the CoMMpass study and characterized immune and hematopoietic cell populations. Associating cell abundances and gene expression with disease progression revealed the presence of a proinflammatory immune senescence-associated secretory phenotype in rapidly progressing patients. Furthermore, signaling analyses suggested active intercellular communication involving APRIL-BCMA, potentially promoting tumor growth and survival. Finally, we demonstrate that integrating immune cell levels with genetic information can significantly improve patient stratification.

genomics↗

bioRxiv2024

Propiconazole and Tianfengsu Regulated the Growth, Flavor, and Nutrition of Brassica rapa by Brassinosteroid Pathway

Propiconazole (PCZ) and Tianfengsu (TFS) are widely used plant growth regulators in vegetable production for improving crop growth, quality, and flavor. This study investigated the effects of PCZ and TFS, applied individually or in combination, on the growth, development, flavor quality, and nutritional components of choy sum (Brassica rapa) and Arabidopsis thaliana, as well as the underlying molecular mechanisms. The results showed that PCZ inhibited the growth of choy sum and Arabidopsis but enhanced the accumulation of flavor compounds such as soluble sugars, proteins, and vitamin C. In contrast, TFS promoted plant growth and increased the content of nutritional components, including chlorophyll and unsaturated fatty acids. Notably, the combined application of PCZ and TFS significantly improved overall plant quality, achieving the optimal balance of flavor and nutritional value while maintaining high yield. Transcriptomic analysis revealed the molecular mechanisms of PCZ and TFS in differentially regulating the expression of brassinosteroid (BR) signaling and downstream metabolism-related genes. Weighted gene co-expression network analysis (WGCNA) further identified key gene modules and hub genes controlling flavor metabolism in choy sum. This study elucidates the synergistic mechanisms of PCZ and TFS in regulating vegetable growth and quality formation, providing valuable insights for the safe production of high-quality choy sum and the development of novel plant growth regulators or elite varieties. HIGHLIGHTSO_LIPCZ and TFS treatments differentially modulate choy sum growth and development by regulating the BR pathway, with PCZ inhibiting while TFS promoting growth. C_LIO_LIPCZ enhances the accumulation of soluble sugars, soluble proteins, and vitamin C, while TFS increases photosynthetic pigments and unsaturated fatty acids, synergistically improving the flavor and nutritional quality of choy sum. C_LIO_LITranscriptomic analysis and WGCNA uncover key genes and modules controlling flavor metabolism in choy sum, providing potential targets for developing novel plant growth regulators or breeding elite varieties C_LI

plant biology↗

bioRxiv2024

Revealing the taxonomy and functional potential of urban soil microbiomes

Urbanization is a leading cause of global biodiversity loss, but its impact on soil microorganisms and biogeochemistry remain uncertain. Although all urban soil microbiomes are influenced by common anthropogenic processes, we lack generalizable patterns in how urbanization impacts the composition and functional potential of the global soil microbiome. These patterns are vital for grasping cities roles in biogeochemical processes and managing urban land expansion. We re-analyze soil metagenomic sequences from the Global Urban Soil Environment Ecology Network (GLUSEEN) to identify coordinated changes in microbial taxonomy and functionality and to pinpoint core taxa and metabolisms across five global cities spanning ecoregions and management regimes. Our findings reveal greater spatial variability in microbial taxonomy compared to functional potential, indicating that common anthropogenic processes might shape the genetic potential of diverse taxa. We identify 111 gene annotations that represent core urban soil functions, present in all cities but rare (<5%) in reference soils. Across low-to-high urban land use gradients; nitrogen, trace/heavy metal, glycerol, and fructose/fructan metabolic processes are linked with highly urbanized areas. Core urban microbial taxa - defined by overrepresentation in urban land uses compared to reference soils - included diverse soil bacteria and a more constrained set of methane- and nitrogen-cycling archaea. Overall, our work aids in deriving testable hypotheses and in modeling the feedbacks between growing metropolitan areas and the processes impacting global environmental change.

microbiology↗

bioRxiv2024

The Ccm3-GckIII signaling axis regulates Rab11-dependent recycling to the apical compartment

Kinase cascades underlie many signaling pathways and are key regulators of development and morphogenesis. We have characterized a Hippo-like kinase cascade consisting of Thousand and One kinase (Tao), Germinal Center Kinase III (GckIII/Wheezy), and Tricornered (Trc) that plays an essential role in morphogenesis of tracheal terminal cell tubes in Drosophila. In this cascade, GckIII is the central kinase and is thought to act together with its binding partner, Cerebral Cavernous Malformations 3 (Ccm3). As suggested by its name, Drosophila Ccm3 is the ortholog of a human vascular disease gene. As such, defining the Ccm3 pathway is critical to understanding both normal development and disease. Here we generate and characterize a null allele of Ccm3 in Drosophila. We uncover a maternal contribution of Ccm3 to embryonic development, show that maternal/zygotic null embryos have defective multicellular tracheal tubes, and that tracheal terminal cells derived from zygotic clones that also lack maternal Ccm3, show fully penetrant tube dilation defects identical to those we previously described for other pathway genes. We show that wildtype Ccm3 colocalizes with p-GckIII during early embryogenesis, and that in larval terminal cells, is found in the nucleus as well as associated with the apical membrane. We further demonstrate that Mouse protein 25 (Mo25), known to encode a protein that binds and stabilizes GckIII proteins in the active conformation, is required to prevent Ccm3-like tube dilations, showing that Mo25 and Ccm3, together with Tao, are required to fully activate GckIII, which directly phosphorylates and activates Tricornered (Trc). We show that this Ccm3 signaling cassette operates in other epithelial tissues such as the wing, and in non-epithelial tissues such as motor neurons. Lastly, we define a role of Ccm3-GckIII signaling in the distribution of active Rab11, leading us to propose that persistent local Rab11 activity results in elevated recycling of membrane and apical determinants to the apical domain, and consequent dilation of tubes. We validate this model by showing that loss of Rab11 activity ameliorates the tube dilation defects of pathway mutants.

developmental biology↗

bioRxiv2024

Seed tuber microbiome is a predictor of next-season potato vigor

Potato vigor, an important agronomic trait, is heavily influenced by the field of seed tuber production. Soil microbiota vary significantly between fields, impacting plant health and crop yield. Our study demonstrates that seed potato vigor can be predicted based on microbiota associated with seed tuber eyes, the dormant buds that grow out in the next season. By combining time-resolved drone-imaging of potato crop development with microbiome sequencing of seed tuber eyes from 6 varieties produced in 240 fields, we established correlations between microbiome fingerprints and potato vigor parameters. Employing Random Forest algorithms, we developed a predictive "Potato-Microbiome Informed" model, revealing variety-specific relationships between seed tuber microbiome composition and next seasons potato vigor in trial fields. The model accurately predicted vigor of seed tubers to which the model was naive and pinpointed key microbial indicators of potato vigor. By connecting variety-specific microbiome fingerprints to crop performance in the field, we pave the way for microbiome-informed breeding strategies.

microbiology↗

bioRxiv2024

Viscoelastic Extracellular Matrix Enhances Epigenetic Remodeling and Cellular Plasticity

Extracellular matrices of living tissues exhibit viscoelastic properties, yet how these properties regulate chromatin and the epigenome remains unclear. Here, we show that viscoelastic substrates induce changes in nuclear architecture and epigenome, with more pronounced effects on softer surfaces. Fibroblasts on viscoelastic substrates display larger nuclei, lower chromatin compaction, and differential expression of distinct sets of genes related to the cytoskeleton and nuclear function compared to those on purely elastic surfaces. Slow-relaxing viscoelastic substrates reduce lamin A/C expression and enhance nuclear remodeling. These structural changes are accompanied by a global increase in euchromatin marks and local increase in chromatin accessibility at cis-regulatory elements associated with neuronal and pluripotent genes. Consequently, viscoelastic substrates improve the reprogramming efficiency from fibroblasts into neurons and induced pluripotent stem cells. Collectively, our findings unravel the roles of matrix viscoelasticity in epigenetic regulation and cell reprogramming, with implications for designing smart materials for cell fate engineering.

cell biology↗

bioRxiv2024

msCNVS: medium throughput single cell copy number variation sequencing with barcoded library construction free of preamplification toward clinical implementation

Single cell copy number variation sequencing (scCNV-seq) is valuable for genomic analysis of a variety of health and disease systems, yet the available methods either depend on either preamplification of the whole genome of each cell, special devices or untracable, which hinder scCNV-seq practice in clinics. Here we provide scalable multiplex scCNV-seq (msCNVS) that allows direct medium-throughput library construction for single cells, which are barcoded individually with Tn5 transposome in a microplate and immediately pooled for downstream processes, elevating the efficiency by orders of magnitude. An algorithm is developed on the distribution of segmented normalized read count density to identify the major peaks associating with integer copy numbers, further improving the accuracy for objective CNV calling. Here msCNVS faithfully distinguishes the unique CNV patterns of 5 cell lines. The individual msCNVS profiles of 70 individual K562 cells highly correlate with the profile of K562 bulk cells (R=0.90-0.98), and the triplicates of HeLa3 bulk cells correlated nearly perfect (R=0.99). The msCNVS CNV profiles of primary cell cultures of amniotic fluid are confirmed by G-banding karyotype analysis and chromosomal microarray analysis. Additionally, the coverage uniformity of msCNVS is superior to that of MDA and MALBAC and approaches what eMDA and DOP-PCR achieves. Furthermore, msCNVS detects CNV deletions in 2 stunted, abnormal blastocysts, one with CNV mosaicism, and uncovered variants of CNVs in circulated tumor cells, cancerous pleural effusion cells, and patient-derived xenograft nuclei. Thus, msCNVS promises a robust, reliable and highly efficient approach to genomic testing of precious and rare cells like those typically obtained in reproductive and cancer clinics. One-Sentence SummaryBy early pooling of multiple single cells individually barcoded with Tn5 transposome, msCNVS enables efficient CNV profiling of rare clinic samples

genomics↗

bioRxiv2024

GenoTools: An Open-Source Python Package for Efficient Genotype Data Quality Control and Analysis

GenoTools, a Python package, streamlines population genetics research by integrating ancestry estimation, quality control (QC), and genome-wide association studies (GWAS) capabilities into efficient pipelines. By tracking samples, variants, and quality-specific measures throughout fully customizable pipelines, users can easily manage genetics data for large and small studies. GenoTools "Ancestry" module renders highly accurate predictions, allowing for high-quality ancestry-specific studies, and enables custom ancestry model training and serialization, specified to the users genotyping or sequencing platform. As the genotype processing engine that powers several large initiatives, including the NIHs Center for Alzheimers and Related Dementias (CARD) and the Global Parkinsons Genetics Program (GP2). GenoTools was used to process and analyze the UK Biobank and major Alzheimers Disease (AD) and Parkinsons Disease (PD) datasets with over 400,000 genotypes from arrays and 5000 sequences and has led to novel discoveries in diverse populations. It has provided replicable ancestry predictions, implemented rigorous QC, and conducted genetic ancestry-specific GWAS to identify systematic errors or biases through a single command. GenoTools is a customizable tool that enables users to efficiently analyze and scale genotype data with reproducible and scalable ancestry, QC, and GWAS pipelines.

genomics↗

bioRxiv2024

How do Large Language Models understand Genes and Cells

Researching genes and their interactions is crucial for deciphering the fundamental laws of biological activity, advancing disease treatment, drug discovery and so on. Large language Models (LLMs), with their profound text comprehension and generation capabilities, have made significant strides across various natural science fields. However, their application in cell biology remains notably scarce. To alleviate this issue, in this paper, we selects seven mainstream LLMs and evaluates their performance across a range of problem scenarios. Our findings indicate that LLMs possess a certain level of understanding of genes and cells, and hold potential for solving real-world problems. Moreover, we have improved the current method of textual representation of cells, enhancing the LLMs ability to tackle cell annotation tasks. We encourage cell biology researchers to leverage LLMs for problem-solving while also being mindful of some challenges associated with their use. We release our code and data at https://github.com/epang-ucas/Evaluate_LLMs_to_Genes. CCS ConceptsApplied computing [->] Recognition of genes and regulatory elements; Bioinformatics; Computational genomics; Computational transcriptomics. ACM Reference FormatChen Fang, Yidong Wang, Yunze Song, Qingqing Long, Wang Lu, Linghui Chen, Pengfei Wang, Guihai Feng, Yuanchun Zhou, and Xin Li. 2024. How do Large Language Models understand Genes and Cells. 1, 1 (March 2024), 14 pages. https://doi.org/10.1145/nnnnnnn.nnnnnnn

bioinformatics↗