Biology subjects

Lu, Z.

Publications and source records attributed to Lu, Z..

At least 127 records · Page 7Linked to original sources

bioRxiv2024

Chromosome-level Subgenome-aware de novo Assembly of Saccharomyces bayanus Provides Insight into Genome Divergence after Hybridization

Interspecies hybridization is prevalent in various eukaryotic lineages and plays important roles in phenotypic diversification, adaption, and speciation. To better understand the changes that occurred in the different subgenomes of a hybrid species and how they facilitated adaptation, we completed chromosome-level de novo assemblies of all 16 pairs chromosomes for a recently formed hybrid yeast, Saccharomyces bayanus strain CBS380 (IFO11022), using Nanopore MinION long-read sequencing. Characterization of S. bayanus subgenomes and comparative analysis with the genomes of its parent species, S. uvarum and S. eubayanus, provide several new insights into understanding genome evolution after a relatively recent hybridization. For instance, multiple recombination events between the two subgenomes have been observed in each chromosome, followed by loss of heterozygosity (LOH) in most chromosomes in nine chromosome pairs. In addition to maintaining nearly all gene content and synteny from its parental genomes, S. bayanus has acquired many genes from other yeast species, primarily through the introgression of S. cerevisiae, such as those involved in the maltose metabolism. In addition, the patterns of recombination and LOH suggest an allotetraploid origin of S. bayanus. The gene acquisition and rapid LOH in the hybrid genome probably facilitated its adaption to maltose brewing environments and mitigated the maladaptive effect of hybridization.

evolutionary biology↗

bioRxiv2024

A Panoramic View of Cell Population Dynamics in Mammalian Aging

To elucidate the aging-associated cellular population dynamics throughout the body, here we present PanSci, a single-cell transcriptome atlas profiling over 20 million cells from 623 mouse tissue samples, encompassing a range of organs across different life stages, sexes, and genotypes. This comprehensive dataset allowed us to identify more than 3,000 unique cellular states and catalog over 200 distinct aging-associated cell populations experiencing significant depletion or expansion. Our panoramic analysis uncovered temporally structured, organ- and lineage-specific shifts of cellular dynamics during lifespan progression. Moreover, we investigated aging-associated alterations in immune cell populations, revealing both widespread shifts and organ-specific changes. We further explored the regulatory roles of the immune system on aging and pinpointed specific age-related cell population expansions that are lymphocyte-dependent. The breadth and depth of our cell-omics methodology not only enhance our comprehension of cellular aging but also lay the groundwork for exploring the complex regulatory networks among varied cell types in the context of aging and aging-associated diseases. One Sentence SummaryPanSci, a single-cell transcriptome atlas of over 20 million cells throughout the mouse lifespan, unveils the temporal architecture of aging-associated cellular population dynamics, organ-specific immune cell shifts, and the lymphocytes role in organismal aging.

genomics↗

bioRxiv2024

MaizeCODE reveals bi-directionally expressed enhancers that harbor molecular signatures of maize domestication.

Modern maize was domesticated from Teosinte parviglumis, with subsequent introgressions from Teosinte mexicana, yielding increased kernel row number, loss of the hard fruit case and dissociation from the cob upon maturity, as well as fewer tillers. Molecular approaches have identified several transcription factors involved in the development of these traits, yet revealed that a complex regulatory network is at play. MaizeCODE deploys ENCODE strategies to catalog regulatory regions in the maize genome, generating histone modification and transcription factor ChIP-seq in parallel with transcriptomics datasets in 5 tissues of 3 inbred lines which span the phenotypic diversity of maize, as well as the teosinte inbred TIL11. Integrated analysis of these datasets resulted in the identification of a comprehensive set of regulatory regions in each inbred, and notably of distal enhancers which were differentiated from gene bodies by their lack of H3K4me1. Many of these distal enhancers expressed non- coding enhancer RNAs bi-directionally, reminiscent of "super enhancers" in animal genomes. We show that pollen grains are the most differentiated tissue at the transcriptomic level, and share features with endosperm that may be related to McClintocks chromosome breakage- fusion-bridge cycle. Conversely, ears have the least conservation between maize and teosinte, both in gene expression and within regulatory regions, reflecting conspicuous morphological differences selected during domestication. The identification of molecular signatures of domestication in transcriptional regulatory regions provides a framework for directed breeding strategies in maize.

plant biology↗

bioRxiv2024

The evolution of 5'UTR length was shaped by natural selection for its functional impact on gene expression

Transcription start site (TSS) marks the first DNA nucleotide of a gene transcribed into RNA. Accumulating evidence suggests that alternative TSS usage (ATU) is widespread across eukaryotes, in response to environmental changes and tissue-specific needs. However, how ATU is coordinated with changes in gene transcription activity and whether it represents a regulated process or merely transcription initiation errors, remains unclear. To address these questions, we conducted integrative analyses of high-resolution TSS maps and translation efficiency data from multiple eukaryotic organisms. Our results reveal that most ATU events co-occur with differential gene expression and that the direction of ATU is largely consistent with changes in transcription levels. These findings suggest that ATU likely works in concert with transcriptional activity to fine-tune protein production, modulating translation efficiency and mRNA stability through alterations in 5'UTR sequence and structural features. Given its functional importance, the evolution of TSS locations may have been shaped by natural selection, leading to heterogeneous 5'UTR lengths in genes with distinct expression demands. This study offers new insights into the complexity of gene regulation and provides a plausible explanation for the highly variable 5'UTR landscape observed within and among eukaryotic genes.

genomics↗

bioRxiv2024

Marine phytoplankton and heterotrophic bacteria rapidly adapt to future pCO2 conditions in experimental co-cultures

The CO2 content of Earths atmosphere is rapidly increasing due to human consumption of fossil fuels. Models based on short-term culture experiments predict that major changes will occur in marine phytoplankton communities in the future ocean, but these models rarely consider how the evolutionary potential of phytoplankton or interactions within marine microbial communities may influence these changes. Here we experimentally evolved representatives of four phytoplankton functional types (silicifiers, calcifiers, coastal cyanobacteria, and oligotrophic cyanobacteria) in co-culture with a heterotrophic bacterium, Alteromonas, under either present-day or predicted future pCO2 conditions. Growth rates of cyanobacteria generally increased under both conditions, and the growth defects observed in ancestral Prochlorococcus cultures at elevated pCO2 and in axenic culture were diminished after evolution, possibly due to regulatory mutations in antioxidant genes. Except for Prochlorococcus, mutational profiles suggested phytoplankton experienced primarily purifying selection, but most Alteromonas lineages showed evidence of directional selection, especially when co-cultured with eukaryotic phytoplankton, where evolution appeared to favor a broad metabolic switch from growth on small organic acids to catabolism of more complex carbon substrates. Evolved Alteromonas were also poorer "helpers" for Prochlorococcus, supporting the assertion that the interaction between Prochlorococcus and heterotrophic bacteria is not a true mutualism but rather a competitive interaction stabilized by Black Queen processes. This work provides new insights on how phytoplankton will respond to anthropogenic change and on the evolutionary mechanisms governing the structure and function of marine microbial communities.

evolutionary biology↗

bioRxiv2024

Diversity, Origin and Evolution of the ESCRT Systems

Endosomal Sorting Complexes Required for Transport (ESCRT) play key roles in protein sorting between membrane-bounded compartments of eukaryotic cells. Homologs of many ESCRT components are identifiable in various groups of archaea, especially in Asgardarchaeota, the archaeal phylum that is currently considered to include the closest relatives of eukaryotes, but not in bacteria. We performed a comprehensive search for ESCRT protein homologs in archaea and reconstructed ESCRT evolution using the phylogenetic tree of Vps4 ATPase (ESCRT IV) as a scaffold, using sensitive protein sequence analysis and comparison of structural models to identify previously unknown ESCRT proteins. Several distinct groups of ESCRT systems in archaea outside of Asgard were identified, including proteins structurally similar to ESCRT-I and ESCRT-II, and several other domains involved in protein sorting in eukaryotes, suggesting an early origin of these components. Additionally, distant homologs of CdvA proteins were identified in Thermoproteales which are likely components of the uncharacterized cell division system in these archaea. We propose an evolutionary scenario for the origin of eukaryotic and Asgard ESCRT complexes from ancestral building blocks, namely, the Vps4 ATPase, ESCRT-III components, wH (winged helix-turn-helix fold) and possibly also coiled-coil, and Vps28-like domains. The Last Archaeal Common Ancestor likely encompassed a complex ESCRT system that was involved in protein sorting. Subsequent evolution involved either simplification, as in the TACK superphylum, where ESCRT was co-opted for cell division, or complexification as in Asgardarchaeota. In Asgardarchaeota, the connection between ESCRT and the ubiquitin system that was previously considered a eukaryotic signature was already established. ImportanceAll eukaryotic cells possess complex intracellular membrane organization. ESCRT (Endosomal Sorting Complexes Required for Transport) plays a central role in membrane remodeling which is essential for cellular functionality in eukaryotes. Recently, it has been shown that Asgard archaea, the archaeal phylum that includes the closest known relatives of eukaryotes, encode homologs of many components of the ESCRT systems. We employed protein sequence and structure comparisons to reconstruct the evolution of ESCRT systems in archaea and identified several previously unknown homologs of ESCRT subunits, some of which can be predicted to participate in cell division. The results of this reconstruction indicate that the Last Archaeal Common ancestor already encoded a complex ESCRT system that was involved in protein sorting. In Asgard archaea, ESCRT systems evolved towards greater complexity, and in particular, the connection between ESCRT and the ubiquitin system that was previously considered a eukaryotic signature was established.

evolutionary biology↗

bioRxiv2024

Assessing NGS-based computational methods for predicting transcriptional regulators with query gene sets

This article provides an in-depth review of computational methods for predicting transcriptional regulators with query gene sets. Identification of transcriptional regulators is of utmost importance in many biological applications, including but not limited to elucidating biological development mechanisms, identifying key disease genes, and predicting therapeutic targets. Various computational methods based on next-generation sequencing (NGS) data have been developed in the past decade, yet no systematic evaluation of NGS-based methods has been offered. We classified these methods into two categories based on shared characteristics, namely library-based and region-based methods. We further conducted benchmark studies to evaluate the accuracy, sensitivity, coverage, and usability of NGS-based methods with molecular experimental datasets. Results show that BART, ChIP-Atlas, and Lisa have relatively better performance. Besides, we point out the limitations of NGS-based methods and explore potential directions for further improvement. Key pointsO_LIAn introduction to available computational methods for predicting functional TRs from a query gene set. C_LIO_LIA detailed walk-through along with practical concerns and limitations. C_LIO_LIA systematic benchmark of NGS-based methods in terms of accuracy, sensitivity, coverage, and usability, using 570 TR perturbation-derived gene sets. C_LIO_LINGS-based methods outperform motif-based methods. Among NGS methods, those utilizing larger databases and adopting region-centric approaches demonstrate favorable performance. BART, ChIP-Atlas, and Lisa are recommended as these methods have overall better performance in evaluated scenarios. C_LI

bioinformatics↗

bioRxiv2024

Disrupting Homologous Recombination or Single-Strand Annealing Significantly Hinders CRISPR-Cas12a-Assisted Nonhomologous End-Joining Gene Editing Efficiency in Mycobacterium abscessus

Mycobacterium abscessus, a fast-growing, non-tuberculous mycobacterium resistant to most antimicrobial drugs, causes many types of serious infections in humans, posing a significant public health challenge. Currently, effective genetic manipulation tools for M. abscessus are still being developed, which hampers research and therapeutic development. However, the clustered regularly interspaced short palindromic repeats (CRISPR) - associated protein (Cas) systems have emerged as promising methods for generating highly specific double-strand breaks (DSBs) in its genome. These DSBs can be repaired by the error-prone nonhomologous end joining (NHEJ) mechanism, facilitating targeted gene editing. Here, our study marks a pioneering application of the CRISPR-NHEJ strategy in M. abscessus. Additionally, we discovered that NrgA from Mycobacterium marinum is crucial for the repair of DSBs caused by the CRISPR-Cas system in M. abscessus. Finally, contrary to previous findings, our study also indicates that inhibiting or overexpressing homologous recombination/single-strand annealing significantly decreases the efficiency of NHEJ repair in M. abscessus. This discovery challenges established perspectives and suggests that the NHEJ repair in M. abscessus may require the involvement of components from homologous recombination and single-strand annealing, demonstrating the complex interactions among the three DSB repair pathways in M. abscessus. Impact statementThere are still very few genetic manipulation tools available for Mycobacterium abscessus. Here we report the successful application of CRISPR-Cas12a-assisted nonhomologous end joining (NHEJ) in efficient gene editing in M. abscessus. Contrary to previous research suggesting that homologous recombination (HR) inhibition may enhance such editing efficiency in other Mycobacterium species, our results showed that disruption or overexpression of either HR or single-strand annealing not only failed to enhance but also significantly reduced the gene editing efficiency in M. abscessus. This suggests that NHEJ repair in M. abscessus may require components from both HR and single-strand annealing, highlighting a complex interaction among the DSB repair pathways in M. abscessus.

microbiology↗

bioRxiv2024

The integration of tandem gene repeats via a bacterial type-II toxin-antitoxin-mediated gene amplification (ToxAmp) system and stability visualisation in Saccharomyces cerevisiae

Tandem gene repeats naturally occur as important genomic features and determine many traits in living organisms, like human diseases and microbial productivities of target bioproducts. Here, we develop a bacterial type-II toxin-antitoxin-mediated method to manipulate genomic integration of tandem gene repeats in Saccharomyces cerevisiae and further visualise the evolutionary trajectories of gene repeats. We designed a tri-vector system to introduce toxin-antitoxin-driven gene amplification (ToxAmp) modules, and accidentally re-visited the high-level capacity of multi-fragment co-transformation in S. cerevisiae. This system delivered the multi-copy gene integration in the form of tandem gene repeats spontaneously and independently from toxin-antitoxin-mediated selection. Inducing the toxin (RelE) expressing via a copper (II)-inducible CUP1 promoter successfully drove the in-situ gene amplification of the antitoxin (RelB) module, resulting in [~]40 copies of a green fluorescence reporter (GFP) gene per copy of genome. The copy-number changes, increasing and decreasing, and stable maintenance were visualised using the GFP and blue chromoprotein AeBlue as reporters. Copy-number increasing happened spontaneously not depending on a selection pressure and was quickly enriched through toxin-antitoxin-mediated selection. In summary, the bacterial toxin-antitoxin systems provide a flexible mechanism to manipulate gene copy number in eukaryotic cells and can be exploited for synthetic biology and metabolic engineering applications. Table of Contents Graphic O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=146 SRC="FIGDIR/small/578080v1_ufig1.gif" ALT="Figure 1"> View larger version (36K): org.highwire.dtl.DTLVardef@75d1f3org.highwire.dtl.DTLVardef@12aafeforg.highwire.dtl.DTLVardef@184a1a5org.highwire.dtl.DTLVardef@90586a_HPS_FORMAT_FIGEXP M_FIG C_FIG

synthetic biology↗

bioRxiv2024

Suppression of epileptic seizures by transcranial activation of K+-selective channelrhodopsin

Optogenetics is a valuable tool for studying the mechanisms of neurological diseases and is now being developed for therapeutic applications. In rodents and macaques, improved channelrhodopsins have been applied to achieve transcranial optogenetic stimulation. While transcranial photoexcitation of neurons has been achieved, noninvasive optogenetic inhibition for treating hyperexcitability-induced neurological disorders has remained elusive. There is a critical need for effective inhibitory optogenetic tools that are highly light-sensitive and capable of suppressing neuronal activity in deep brain tissue. In this study, we developed a highly sensitive K+-conductive channelrhodopsin (hsKCR) by molecular engineering of the recently discovered Hyphochytrium catenoides kalium (potassium) channelrhodopsin 1. Transcranial activation of hsKCR significantly prolongs the time to the first seizure, increases survival, and decreases seizure activity in several mouse epileptic models. Our approach for transcranial optogenetic inhibition of neural hyperactivity may be adapted for cell type-specific neuromodulation in both basic and preclinical settings.

neuroscience↗

bioRxiv2023

Spatial transcriptomics of a parasitic flatworm provides a molecular map of vaccine candidates, drug targets and drug resistance genes

The spatial organization of gene expression dictates tissue functions in multicellular parasites. Here, we present the first spatial transcriptome of a parasitic flatworm, the common liver fluke Fasciola hepatica. We identified gene expression profiles and marker genes for eight distinct tissues and validated the latter by in situ hybridization. To demonstrate the power of our spatial atlas, we focused on genes with substantial medical importance, including vaccine candidates (Ly6 proteins), drug targets ({beta}-tubulins, protein kinases) and drug resistance genes (glutathione S-transferases, ABC transporters). Several of these genes exhibited unique expression patterns, indicating tissue-specific biological functions. Notably, the prioritization of tegumental protein kinases identified a PKC{beta}, for which small-molecule targeting caused parasite death. Our comprehensive gene expression map provides unprecedented molecular insights into the organ systems of this complex parasitic organism, serving as a valuable tool for both basic and applied research.

molecular biology↗

bioRxiv2023

Recreating the Biological Steps of Viral Infection on a Bioelectronic Platform to Profile Viral Variants of Concern

Viral mutation rates frequently outpace the development of technologies used to detect and identify harmful variants; for SARS Coronavirus-2 (SARS-CoV-2), these are called variants of concern (VOC). Given the continual emergence of VOC, there is a critical need to develop platforms that can identify the presence of a virus and readily identify its propensity for infection. We present an electronic biomembrane sensing platform that recreates the multifaceted and sequential biological cues that give rise to distinct SARS-CoV-2 virus host cell entry pathways and reports the progression of entry steps of these pathways as electrical signals. Within these electrical signals, two necessary entry processes mediated by the viral Spike protein, virus binding and membrane fusion, can be distinguished. Remarkably, we find that closely related VOC exhibit distinct fusion signatures that correlate with trends reported in cell-based infectivity assays, allowing us to report quantitative differences in fusion characteristics among them that inform their infectivity potentials. This cell-free biomimetic infection platform also has a virus-free option that equally reports infectivity potential of the Spike proteins. We used SARS-CoV-2 as our prototype, but we anticipate that this platform will extend to other enveloped viruses and cell lines to quantifiably explore virus/host interactions. This advance should aid in faster determination of entry characteristics and fusogenicities of future VOC, necessary for rapid response.

bioengineering↗

bioRxiv2023

Polymer Implantable Electrode Foundry: A shared resource for manufacturing polymer-based microelectrodes for neural interfaces

Large scale monitoring of neural activity at the single unit level can be achieved via electrophysiological recording using implanted microelectrodes. While neuroscience researchers have widely employed chronically implanted electrode-based interfaces for this purpose, a commonly encountered limitation is loss of highly resolved signals arising from immunological response over time. Next generation electrode-based interfaces improve longitudinal signal quality using the strategy of stabilizing the device-tissue interface with microelectrode arrays constructed from soft and flexible polymer materials. The limited availability of such polymer microelectrode arrays has restricted access to a small number of researchers able to build their own custom devices or who have developed specific collaborations with engineering researchers who can produce them. Here, a new technology resource model is introduced that seeks to widely increase access to polymer microelectrode arrays by the neuroscience research community. The Polymer Implantable Electrode (PIE) Foundry provides custom and standardized polymer microelectrode arrays as well as training and guidance on best-practices for implantation and chronic experiments.

neuroscience↗

bioRxiv2023

Brief change in dopamine activity during consolidation impairs long-term memory via sleep disruption

Sleep disturbances are associated with poor long-term memory (LTM) formation, yet the underlying cell types and neural circuits involved have not been fully decoded. Dopamine neurons (DANs) are involved in memory processing at multiple stages. Here, using both male and female flies, Drosophila melanogaster, we show that, during the first few hours of memory consolidation, disruption of basal activity of a small subset of protocerebral anterior medial DANs (PAM-DANs), by either brief activation or inhibition of the two dorsal posterior medial (DPM) neurons, impairs 24 h LTM. Interestingly, these brief changes in activity using female flies result in sleep loss and fragmentation, especially at night. Importantly, pharmacological rescue of sleep after manipulation restores LTM. A specific subset of PAM-DANs (PAM-1) that synapse onto DPM neurons specify the microcircuit that links sleep and memory. MBON-1 also contributes to the integration of sleep and memory by acting as an additional parallel circuit. PAM-DANs, including PAM-1, form functional synapses onto DPM mainly via two dopamine receptor subtypes. Dop1R1 primarily mediates the link between sleep and memory. This PAM-1 to DPM microcircuit exhibits a synchronized, transient, post-training change in activity during the critical memory consolidation window, suggesting an effect of this microcircuit on maintaining the sleep necessary for LTM consolidation. Our results provide a new molecular and circuit basis for the complex relationship between sleep and memory.

neuroscience↗

bioRxiv2023

Scale-independent topological interactions drive the first fate decision in the Drosophila embryo

During embryogenesis, the earliest cell fate decision is often linked to nuclear positioning, whose control arises from the integration of the cell cycle oscillator and associated cytoskeletal dynamics. Yet, the mechanisms that ensure that the correct number of nuclei move to the appropriate place remain poorly understood. Here, using light sheet microscopy, we show that in Drosophila embryos spindle orientation controls which nuclei migrate towards the cortex and which remains inside the embryo, thereby determining nuclear fate and the number of cells undergoing development. Combining computational methods inspired by integral geometry and manipulations of cell cycle genes, we show that spindle orientation is controlled by topological spindle-spindle interactions and not by internuclear distance. Using arguments describing the behavior of space-filling systems, we develop a theory for topological dependency in microtubule structures. Our work shows how topological interplay of microtubule mechanics can ensure robust control of density and cell fate determination.

developmental biology↗

bioRxiv2023

Trogocytosis of cancer-associated fibroblasts promotes pancreatic cancer growth and immune suppression via phospholipid scramblase anoctamin 6 (ANO6).

In pancreatic ductal adenocarcinoma (PDAC), the fibroblastic stroma constitutes most of the tumor mass and is remarkably devoid of functional blood vessels. This raises an unresolved question of how PDAC cells obtain essential metabolites and water-insoluble lipids. We have found a critical role for cancer-associated fibroblasts (CAFs) in obtaining and transferring lipids from blood-borne particles to PDAC cells via trogocytosis of CAF plasma membranes. We have also determined that CAF-expressed phospholipid scramblase anoctamin 6 (ANO6) is an essential CAF trogocytosis regulator required to promote PDAC cell survival. During trogocytosis, cancer cells and CAFs form synapse-like plasma membranes contacts that induce cytosolic calcium influx in CAFs via Orai channels. This influx activates ANO6 and results in phosphatidylserine exposure on CAF plasma membrane initiating trogocytosis and transfer of membrane lipids, including cholesterol, to PDAC cells. Importantly, ANO6-dependent trogocytosis also supports the immunosuppressive function of pancreatic CAFs towards cytotoxic T cells by promoting transfer of excessive amounts of cholesterol. Further, blockade of ANO6 antagonizes tumor growth via disruption of delivery of exogenous cholesterol to cancer cells and reverses immune suppression suggesting a potential new strategy for PDAC therapy.

cancer biology↗

bioRxiv2023

Heterogeneity and genomic evolution of metastatic prostate cancer

BackgroundMetastasis is the primary cause of prostate cancer-related deaths. However, the underlying molecular mechanisms and evolutionary patterns remain largely uncharacterized. MethodsWe evaluate the heterogeneity and genomic evolution of prostate cancer with multi-organ metastases. The samples include 32 primary samples, 23 lymph node metastases, 22 bone metastases, 16 liver metastases, and four pelvic mess metastases. They are analyzed to identify the mutated genes enriched in metastatic samples, selected by metastases, and leading to different long-distance migrations. These metastasis-related alterations constitute a Mscore for evaluating the metastatic risk of primary prostate tumors. ResultsOur analysis discovers 21 metastasis-related mutated genes in total. Of them, 14 genes are finally selected for metastatic risk prognosis, including the mutations of AR and KMT2C with high prediction ability. A Mscore established with these 14 characteristics by the xgboost model displays its ability to classify primary tumors and metastases. This score can further divide primary prostate tumors from the TCGA cohort into two groups. The two subsets present significantly differential survival risks. This score can also identify metastasis-featured primary tumors for breast cancer, bladder cancer, liver cancer, and uterine corpus endometrial carcinoma. ConclusionOur research proposes 14 molecular features potentially driving prostate cancer metastasis. The Mscore established on them can estimate the metastatic risk of primary tumors.

bioinformatics↗

bioRxiv2023

Human EEG and artificial neural networks reveal disentangled representations of object real-world size in natural images

Remarkably, human brains have the ability to accurately perceive and process the real-world size of objects, despite vast differences in distance and perspective. While previous studies have delved into this phenomenon, distinguishing the processing of real-world size from other visual properties, like depth, has been challenging. Using the THINGS EEG2 dataset with human EEG recordings and more ecologically valid naturalistic stimuli, our study combines human EEG and representational similarity analysis to disentangle neural representations of object real-world size from retinal size and perceived depth, leveraging recent datasets and modeling approaches to address challenges not fully resolved in previous work. We report a representational timeline of visual object processing: object real-world depth processed first, then retinal size, and finally, real-world size. Additionally, we input both these naturalistic images and object-only images without natural background into artificial neural networks. Consistent with the human EEG findings, we also successfully disentangled representation of object real-world size from retinal size and real-world depth in all three types of artificial neural networks (visual-only ResNet, visual-language CLIP, and language-only Word2Vec). Moreover, our multi-modal representational comparison framework across human EEG and artificial neural networks reveals real-world size as a stable and higher-level dimension in object space incorporating both visual and semantic information. Our research provides a temporally resolved characterization of how certain key object properties - such as object real-world size, depth, and retinal size - are represented in the brain, which offers further advances and insights into our understanding of object space and the construction of more brain-like visual models.

neuroscience↗