Search bioRxiv⌕ Search

SEARCH · Search bioRxiv

Results for “Systems Biology”

Search indexed bioRxiv preprints in genomics, neuroscience, cell biology and bioinformatics. Read source abstracts and check manuscript versions; preprints are not peer reviewed.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,657 records · Page 92Linked to original sources

Quantifying Scientific Consensus in Biomedical Hypotheses via LLM-Assisted Literature Screening

Systematic literature reviews are labor-intensive tasks in biomedical research. While Large Language Models (LLMs) using Retrieval-Augmented Generation (RAG) techniques have enhanced information accessibility, the inherent complexity of biological systems--characterized by high context dependency and conflicting data--remains a primary driver of LLM hallucinations. This imposes a structural constraint that limits the precision of evidence synthesis. To address these limitations, we propose an automated framework designed for the exhaustive identification of supporting and contradictory evidence within a target literature set. Rather than relying on a models pre-trained knowledge, our system requires the LLM to review each paper individually to determine its alignment with a specific research hypothesis. By evaluating semantic context, the framework captures subtle contradictions that are often overgeneralized by conventional methods. The frameworks performance was validated using the BioNLI task, where it demonstrated high classification accuracy in distinguishing whether evidence supports or contradicts a given hypothesis. Notably, the implementation of an ensemble approach provided superior stability and slightly higher precision compared to individual models. Furthermore, the framework exhibited robust performance across several well-established biological hypotheses, confirming its practical utility and reliability in real-world research. This approach provides a rigorous basis for biomedical discovery by enabling the precise, systematic analysis of biological literature and the robust collection of evidence.

bioinformatics↗

A Bioluminescent Assay for Quantification of Cellular Glycogen Levels

Glycogen is a large polymer of glucose that functions as an important means of storing energy and maintaining glucose homeostasis. Glycogen synthesis and degradation pathways are highly regulated and their dysregulation can contribute to disease. Glycogen storage diseases are a set of disorders that arise from improper glycogen metabolism. Glycogen storage disease II, known as Pompe disease, is caused by a genetic mutation that leads to increased glycogen storage in cells and tissues, resulting in progressive muscle atrophy and respiratory decline for patients. One approach for treating Pompe disease is to reduce glycogen levels by interfering with the glycogen synthesis pathway through glycogen synthase inhibitors. To facilitate the study of glycogen synthase inhibitors in biological samples, such as cultured cells, a high-throughput approach for measuring cellular glycogen was developed. A bioluminescent glycogen detection assay was automated and used to measure glycogen content in cells grown in 384-well plates. The assay successfully quantified reduced glycogen stores in cells treated with a series of glycogen synthase 1 inhibitors, verifying inhibitor activity in biological systems and validating the utility of the assay for glycogen metabolism studies. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=90 SRC="FIGDIR/small/595028v1_ufig1.gif" ALT="Figure 1"> View larger version (15K): org.highwire.dtl.DTLVardef@1ae263borg.highwire.dtl.DTLVardef@50124eorg.highwire.dtl.DTLVardef@e1ca53org.highwire.dtl.DTLVardef@1aa41dc_HPS_FORMAT_FIGEXP M_FIG C_FIG

cell biology↗

NetREX: Network Rewiring using EXpression - Towards Context Specific Regulatory Networks

Understanding gene regulation is a fundamental step towards understanding of how cells function and respond to environmental cues and perturbations. An important step in this direction is the ability to infer the transcription factor (TF)-gene regulatory network (GRN). However gene regulatory networks are typically constructed disregarding the fact that regulatory programs are conditioned on tissue type, developmental stage, sex, and other factors. Due to lack of the biological context specificity, these context-agnostic networks may not provide insight for revealing the precise actions of genes for a specific biological system under concern. Collecting multitude of features required for a reliable construction of GRNs such as physical features (TF binding, chromatin accessibility) and functional features (correlation of expression or chromatin patterns) for every context of interest is costly. Therefore we need methods that is able to utilize the knowledge about a context-agnostic network (or a network constructed in a related context) for construction of a context specific regulatory network.\n\nTo address this challenge we developed a computational approach that utilizes expression data obtained in a specific biological context such as a particular development stage, sex, tissue type and a GRN constructed in a different but related context (alternatively an incomplete or a noisy network for the same context) to construct a context specific GRN. Our method, NetREX, is inspired by network component analysis (NCA) that estimates TF activities and their influences on target genes given predetermined topology of a TF-gene network. To predict a network under a different condition, NetREX removes the restriction that the topology of the TF-gene network is fixed and allows for adding and removing edges to that network. To solve the corresponding optimization problem, which is non-convex and non-smooth, we provide a general mathematical framework allowing use of the recently proposed Proximal Alternative Linearized Maximization technique and prove that our formulation has the properties required for convergence.\n\nWe tested our NetREX on simulated data and subsequently applied it to gene expression data in adult females from 99 hemizygotic lines of the Drosophila deletion (DrosDel) panel. The networks predicted by NetREX showed higher biological consistency than alternative approaches. In addition, we used the list of recently identified targets of the Doublesex (DSX) transcription factor to demonstrate the predictive power of our method.

bioinformatics↗

Enzymatic activity induces transient non-spherical coacervate shapes

Coacervates are polymer-rich droplets that form through liquid-liquid phase separation in polymer solutions. Liquid-liquid phase separation and coacervation have recently been shown to play an important role in the organization of biological systems. Such systems are highly dynamic and under continuous influence of enzymatic and chemical processes. However, it is still unclear how enzymatic and chemical reactions affect the coacervation process. Here, we present and characterize a system of enzymatically active coacervates containing spermine, RNA, free nucleotides, and the template independent RNA (de)polymerase PNPase. We find that these RNA coacervates display transient non-spherical shapes, and we systematically study how PNPase concentration, UDP concentration and temperature affect coacervate morphology. Furthermore, we show that PNPase localizes predominantly into the coacervate phase and that its depolymerization activity in high-phosphate buffer causes coacervate degradation. Our observations of non-spherical coacervate shapes may have broader implications for the relationship between (bio-)chemical activity and coacervate biology.

biophysics↗

Dysregulation of the secretory pathway connects Alzheimer's disease genetics to aggregate formation

A hallmark of amyloid disorders, such as Alzheimers disease, is aggregation of secreted proteins. However, it is largely unclear how the hundreds of secretory pathway proteins contribute to amyloid formation. We developed a systems biology framework that integrates expression data with protein-protein interaction networks to successfully estimate a tissues fitness for producing specific secreted proteins. Using this framework, we analyzed the fitness of the secretory pathway of various brain regions and cell types for synthesizing the Alzheimers disease-associated amyloid-precursor protein (APP). While none of the key amyloidogenic pathway components were differentially expressed in AD brain, we found the deposition of A{beta} is associated with repressed expression of the secretory pathway components proximal to APP. Concurrently, we detected systemic up-regulation of the secretory pathway components proximal to {beta}- and {gamma}-secretases in AD brains. Our analyses suggest that perturbations from 3 high confidence AD risk genes cascade through the secretory machinery support network for APP and into the endocytosis pathway. Thus, we present a model where amyloidogenesis is associated with dysregulation of dozens of secretory pathway components supporting APP, which could yield novel therapeutic targets for the treatment of AD.

neuroscience↗

Filter inference: A scalable nonlinear mixed effects inference approach for snapshot time series data

Variability is an intrinsic property of biological systems and is often at the heart of their complex behaviour. Examples range from cell-to-cell variability in cell signalling pathways to variability in the response to treatment across patients. A popular approach to model and understand this variability is nonlinear mixed effects (NLME) modelling. However, estimating the parameters of NLME models from measurements quickly becomes computationally expensive as the number of measured individuals grows, making NLME inference intractable for datasets with thousands of measured individuals. This shortcoming is particularly limiting for snapshot datasets, common e.g. in cell biology, where high-throughput measurement techniques provide large numbers of single cell measurements. We extend earlier work by Hasenauer et al (2011) to introduce a novel approach for the estimation of NLME model parameters from snapshot measurements, which we call filter inference. Filter inference is a new variant of approximate Bayesian computation, with dominant computational costs that do not increase with the number of measured individuals, making efficient inferences from snapshot measurements possible. Filter inference also scales well with the number of model parameters, using state-of-the-art gradient-based MCMC algorithms, such as the No-U-Turn Sampler (NUTS). We demonstrate the properties of filter inference using examples from early cancer growth modelling and from epidermal growth factor signalling pathway modelling. Author summaryNonlinear mixed effects (NLME) models are widely used to model differences between individuals in a population. In pharmacology, for example, they are used to model the treatment response variability across patients, and in cell biology they are used to model the cell-to-cell variability in cell signalling pathways. However, NLME models introduce parameters, which typically need to be estimated from data. This estimation becomes computationally intractable when the number of measured individuals - be they patients or cells - is too large. But, the more individuals are measured in a population, the better the variability can be understood. This is especially true when individuals are measured only once. Such snapshot measurements are particularly common in cell biology, where high-throughput measurement techniques provide large numbers of single cell measurements. In clinical pharmacology, datasets consisting of many snapshot measurements are less common but are easier and cheaper to obtain than detailed time series measurements across patients. Our approach can be used to estimate the parameters of NLME models from snapshot time series data with thousands of measured individuals.

bioinformatics↗

Identifying a Vaginal Microbiome-Derived Selective Antibiotic Metabolite via Microbiome Pharmacology Analysis

The vaginal microbiome plays a critical role in maintaining immune and epithelial homeostasis in the female reproductive tract. Bacterial Vaginosis (BV) is deleterious to female health, causing the loss of beneficial Lactobacillus species, overgrowth of anaerobic taxa, changes in vaginal pH, breakdown of protective mucins and epithelial barriers, and activation of the immune system. Treatment with gel-based antibiotics (Metronidazole or Clindamycin) resolves BV for 85% of patients, but 50% of those cases recur, indicating a need to identify strategies for overcoming antibiotic resistance and achieving a more durable response. Here, we developed a systems biology approach termed Microbiome Pharmacology Analysis to characterize the antibiotic potential of vaginal microbes, their metabolites and functions, via computational fusion of human cohort multi-omics and post-drug perturbation transcriptomic profiles. We focused on Clindamycin and Metronidazole as candidate drugs and screened 780 vaginal microbiome-drug mimicry candidates to identify candidate taxa and metabolites with antibiotic potential. We demonstrate experimentally that Lactobacillus crispatus-derived Hydroxyisocaproate (HICA) selectively kills Gardnerella vaginalis and that HICA enhances epithelial barrier integrity in a human vagina-on-a-chip system. Our work demonstrates the first use of Pharmacobiome Analysis, for discovering novel, selective antibiotic metabolites for BV with implications for charting the full pharmacologic potential of the vaginal microbiome.

microbiology↗

Invariants of Frameshifted Variants

Frameshifts in protein coding sequences are widely perceived as resulting in either non-functional or even deleterious protein products. Indeed, frameshifts typically lead to markedly altered protein sequences and premature stop codons. By analyzing complete proteomes from all three domains of life, we demonstrate that, in contrast, several key physicochemical properties of protein sequences exhibit significant robustness against +1 and -1 frameshifts in their mRNA coding sequences. In particular, we show that hydrophobicity profiles of many protein sequences remain largely invariant upon frameshifting. For example, over 2900 human proteins exhibit a Pearson correlation coefficient between the hydrophobicity profiles of the original and the +1-frameshifted variants greater than 0.7, despite a median sequence identity between the two of only 6.5% in this group. We observe a similar effect for protein sequence profiles of affinity for certain nucleobases, their matching with the cognate mRNA nucleobase-density profiles as well as protein sequence profiles of intrinsic disorder. Finally, we show that frameshift invariance is directly embedded in the structure of the universal genetic code and may have contributed to shaping it. Our results suggest that frameshifting may be a powerful evolutionary mechanism for creating new proteins with vastly different sequences, yet similar physicochemical properties to the proteins they originate from.\n\nSignificance StatementGenetic information stored in DNA is transcribed to messenger RNAs and then read in the process of translation to produce proteins. A frameshift in the reading frame at any stage of the process typically results in a significantly different protein sequence being produced and is generally assumed to be a source of detrimental errors that biological systems need to control. Here, we show that several essential properties of many protein sequences, such as their hydrophobicity profiles, remain largely unchanged upon frameshifts. This finding suggests that frameshifting could be an effective evolutionary strategy for generating novel protein sequences, which retain the functionally relevant physicochemical properties of the sequences they derive from.

molecular biology↗

The formation of the Indo-Pacific montane avifauna

Mountain biotas have considerable conservation and research importance, but the formation of montane communities remains incompletely understood. Study of Indo-Pacific island faunas has inspired two main hypotheses for the generation of montane diversity. The first posits that montane populations arise via direct colonization from other mountain areas, while the second invokes recruitment from adjacent lowland populations. We sought to reconcile these apparently conflicting hypotheses by asking whether a species ancestral geographic origin determines its mode of mountain colonization. To this end, island-dwelling passerine birds at the faunal crossroads between Eurasia and Australo-Papua provide an ideal study system. We recovered the phylogenetic relationships of the regions montane species, and used this information to reconstruct their ancestral geographic ranges, elevational ranges, and migratory behavior. We also performed genomic population studies of three super-dispersive montane species/clades with broad island distributions. Eurasian-origin species populated archipelagos via direct colonization between mountains. This mode of colonization appears related to ancestral adaptations to cold and seasonal Palearctic climates, specifically short-distance migration. Australo-Papuan-origin mountain populations, by contrast, evolved from lowland ancestors, and highland distribution mostly precludes their further colonization of island mountains. The patterns and processes revealed for this group are compatible with taxon cycles, a hypothesized process of lowland lineage expansion followed by montane relictualization. Collectively, our analyses explain much of the distributional variation within a complex biological system, and provide a synthesis of two seemingly discordant hypotheses for montane community formation.

evolutionary biology↗

Urinary Metabolomic Profile is Minimally Impacted by Common Storage Conditions and Additives

Metabolomics reflects the molecular communications within a biological system. Urine can be obtained non-invasively and is rich in metabolites that are potential biomarkers for human health and disease. The optimal urine storage conditions for metabolomic analysis are unknown. We measured the impact of common storage conditions and the presence of a DNA-stabilizer, AssayAssure(R) (Thermo Scientific), on metabolite content of voided human urine. Urinary metabolite composition was not altered across storage conditions. Although addition of AssayAssure(R) significantly alters metabolic profile by adduct addition, this does not preclude the identification of parent metabolites or overshadow biological differences. These data suggest biobanked urine stored in any of the tested conditions for metabolomic studies may be considered for metabolomic analysis.

molecular biology↗

Proteomic Organellar Mapping Reveals Modulation of Peroxisomes by HIV-1

As systems biology approaches to virology have become more tractable, highly studied viruses such as HIV can now be analyzed in new, unbiased ways, including spatial proteomics. We employed here a differential centrifugation protocol to fractionate Jurkat T cells for proteomic analysis by mass spectrometry; these cells contain inducible HIV-1 genomes, enabling us to look for changes in the spatial proteome induced by viral gene expression. Using these proteomics data, we evaluated the merits of several reported machine learning pipelines for classification of the spatial proteome and identification of protein translocations. From these analyses we found that classifier performance in this system was organelle-dependent, with Bayesian t-augmented Gaussian mixture modeling outperforming support vector machine (SVM) learning for mitochondrial and ER proteins, but underperforming on cytosolic, nuclear, and plasma membrane proteins by QSep analysis. We also observed a generally higher performance for protein translocation identification using a Bayesian model, BANDLE, on SVM-classified data. Comparative BANDLE analysis of cells induced to express the wild-type viral genome vs. cells induced to express a genome unable to express the accessory protein Nef identified known Nef-dependent interactors such as TCR signaling components and coatomer complex. Lastly, we found that SVM classification showed higher consistency and was less sensitive to HIV-dependent noise. These findings illustrate important considerations for studies of the spatial proteome following viral infection or viral gene expression and provide a reference for future studies of HIV-gene-dropout viruses.

cell biology↗

The Evolutionary Landscape of Pan-Cancer Drives Clinical Aggression

Although cancer mechanisms differ from occurrence and development, some of them have similar oncogenesis, which leads to similar clinical phenotypes. Most existing genotyping studies look at \"omics\" data, but intentionally or unintentionally avoided that cancer is a time-dependent evolutionary process, biologically represented by the time evolution of tumor clones. We used the Bayesian mutation landscape approach to reconstruct the evolutionary process of cancer by acquiring somatic mutation data consisting of 21 cancer types. Four representative evolution patterns of pan-cancer have been discovered: trees, chaos, biconvex, and Cambrian, and a strong correlation between these four evolutionary patterns and clinical aggressivity. We further explained the characteristics of the corresponding biological systems in the evolution of pan cancer by analyzing the function of differentially expressed protein-protein interaction networks. Our results explained the difference in clinical aggressivity between cancer evolution patterns from the evolution of tumor clones and exposed the functional mechanism behind.

cancer biology↗

Super-resolved polarisation-enhanced second harmonic generation for direct imaging of nanoscale changes in collagen architecture

Super-resolution (SR) optical microscopy has allowed the investigation of many biological structures below the diffraction limit, however, most of the techniques are hampered by the need for fluorescent labels. Non-linear label-free techniques such as Second Harmonic Generation (SHG) provide structurally specific contrast without the addition of exogenous labels, allowing observation of unperturbed biological systems. Here we achieve super-resolution SHG (SR-SHG) for the first time. We use the photonic nanojet (PNJ) phenomena to achieve a resolution of ~{lambda}/6 with respect to the fundamental wavelength, a ~2.7-fold improvement over diffraction-limited SHG under the same imaging conditions. Crucially we find that the polarisation properties of excitation are maintained in a PNJ allowing the resolution to be further enhanced by detection of polarisation-resolved SHG (p-SHG) by observing anisotropy in signals. These new findings allowed us to visualise biological SHG-active structures such as collagen at an unprecedented and previously unresolvable spatial scale. Moreover, we demonstrate that the use of an array of self-assembled high-index spheres overcomes the issue of a limited field of view for such a method, allowing PNJ-assisted SR-SHG to be used over a large area. Dysregulation of collagen at the nanoscale occurs in many diseases and is an underlying cause in diseases such as lung fibrosis. Here we are able to demonstrate that pSR-SHG allows unprecedented observation of changes at the nanoscale that are invisible by conventional diffraction-limited SHG imaging. The ability to non-destructively image SHG-active biological structures without labels at the nanoscale with a relatively simple optical method heralds the promise of a new tool to understand biological phenomena and drive drug discovery.

biophysics↗

High-throughput chemical proteomics workflow for profiling protein citrullination dynamics

Citrullination is a post-translational modification implicated in autoimmune and inflammatory diseases, yet its low abundance and lack of effective enrichment tools have limited proteome-wide analysis. Here, we developed a robust chemical proteomics workflow with improved specificity and throughput. This method builds upon glyoxal-based derivatization and incorporates a cleavable biotin linker for efficient peptide enrichment, release, and identification via mass spectrometry. Benchmarking across biological systems demonstrated a >10-fold increase in the detection of citrullinated peptides (> 150-fold increase in intensity) at sub-0.1% abundance. Applying the workflow to mouse brain tissue and human primary neutrophils revealed dynamics and condition-specific changes in the citrullinome, including previously uncharacterized sites and regulatory processes. Notably, extensive citrullination of linker histone H1 and structural proteins such as lamin B1 in ionomycin-activated neutrophils suggests broad remodeling of cell architecture via citrullination. This workflow enables proteome-wide mapping of citrullination sites and facilitates its study across diverse biological contexts.

biochemistry↗

CRISPR interference as low burden logic inverters in synthetic circuits: characterization and tuning

The rational design of complex biological systems through the interconnection of single functional building blocks is hampered by many unpredictability sources; this is mainly due to the tangled context-dependency behavior of those parts once placed into an intrinsically complex living system. Among others, the finite amount of translational resources in prokaryotic cells leads to load effects in heterologous protein expression. As a result, hidden interactions among protein synthesis rates arise, leading to unexpected and counterintuitive behaviors. To face this issue in rational design of synthetic circuits in bacterial cells, CRISPR interference is here evaluated as genetic logic inverters with low translational resource usage, compared with traditional transcriptional regulators. This system has been studied and characterized in several circuit configurations. Each module composing the circuit architecture has been optimized in order to meet the desired specifications, and its reduced metabolic load has been eventually demonstrated via in-vivo assays.

synthetic biology↗

A-Star, an Argonaute-directed System for Rare SNV Enrichment and Detection

The ability to detect rare mutations has revolutionized diagnosis and monitoring of tumors, but is limited by the shortage of sensitive, cost-effective and high coverage methods for identification of extremely low abundant mutations. Here, we establish a single-tube multiplex PCR system by employing thermophilic Argonaute-derived DNA-guided nuclease for highly efficient rare mutation detection, referred to as A-Star (Argonaute-directed specific target enrichment and detection), that combines the selective cleavage of the wild type DNA in the DNA denaturation step and the followed amplification of mutant DNA during PCR. A-Star enables easy detection and quantitation of rare mutations originally as low as 0.01% in allele frequency with a [>=] 5500-fold efficiency. We also demonstrate the feasibility of A-Star for detecting oncogenic mutations in complex biological systems such as solid tumors tissues and blood samples. Remarkably, A-Star could achieve the detection of multiple oncogenic genes simultaneously through a simple single-tube reaction. Taken together, our work illustrates a supersensitive and rapid nucleic acid detection system, thereby extending the utility for both research and therapeutic applications.

bioengineering↗

ICON: An isoform-aware hierarchical random forest model for cell type classification

Single-cell RNA sequencing (scRNA-seq) has transformed our ability to resolve cellular heterogeneity across complex biological systems. However, conventional short-read scRNA-seq is inherently limited in its inability to capture full-length transcripts. Isoform profiles, arising from alternative splicing, provide a deeper layer of resolution, enabling finer discrimination of cellular subtypes and dynamic states, particularly in heterogenous tissues. Long-read RNA sequencing technologies enable accurate transcript-level profiling and more comprehensive characterisation of isoform diversity. Despite these advances, existing cell type annotation methods remain largely tailored to gene-level data, thereby limiting fidelity and leaving isoform-level information an untapped reservoir of biological insight. Here, we present a hierarchical random forest (HRF) framework, ICON, for isoform-aware cell classification in scRNA-seq data. By jointly modelling gene- and isoform-level expression the framework captures both abundance and useage patterns, enabling classification beyond gene-level resolution. A two-stage strategy first assigns cell identities using highly variable gene and isoform features, followed by targeted reclassification of ambiguous cells based on relative isoform and gene usage, thereby resolving conflicts that arise from transcriptional heterogeneity. Importantly, ICON provides interpretable outputs by identifying key genes and isoforms that drive cell type discrimination, linking classification to underlying regulatory mechanisms. Benchmarking on long-read scRNA-seq datasets demonstrates consistent improvements over conventional gene-based approaches. With increasing adoption of long-read sequencing, our framework provides a robust, interpretable foundation for isoform-aware cell type annotation, improving resolution and insight.

bioinformatics↗

Quantifying temperature compensation of Bicoid gradients with a fast T-tunable microfluidic device

As a reaction-diffusion system strongly affected by temperature, the early fly embryos surprisingly show highly reproducible and accurate developmental patterns during embryogenesis under temperature perturbations. To reveal the underlying temperature compensation mechanism, it is important to overcome the challenge in quantitative imaging on fly embryos under temperature perturbations. Inspired by a microfluidics generating temperature steps on fly embryos, here we design a microfluidic device capable of ensuring the normal development of multiple fly embryos as well as achieving real-time temperature control and fast temperature jumps for quantitative live imaging with a home-built two-photon microscope. We apply this system to quantify the temperature compensation of the morphogen Bicoid (Bcd) gradient in fly embryos. The length constant of the exponential Bcd gradient reaches the maximum at 25 {degrees}C within the measured temperatures of 18-29 {degrees}C and gradually adapts to the corresponding value at new temperatures upon a fast temperature switch. Such an adaption decreases to a less degree if temperature is switched in a later developmental stage. This age-dependent temperature compensation could not be explained with the traditional synthesis-diffusion-degradation (SDD) model assuming the static parameters but an extended SDD model incorporating the dynamic change of the parameters controlling the formation of Bcd gradients. SIGNIFICANCEThermal robustness is important for biological systems experiencing temperature fluctuations. To reveal the temperature compensation mechanism, the fruit fly embryo is an ideal model system. It is intriguing how the early fly embryo achieves highly reproducible and accurate patterning despite it is a reaction-diffusion system strongly affected by temperature. However, it has been challenging to quantitatively measure the developmental patterns in fly embryos under temperature perturbations. To overcome this problem, we construct a fast temperature tunable microfluidic device for fly embryos. Combining quantitative imaging with this device and mathematical modeling, we successfully quantify the temperature response of the morphogen Bicoid (Bcd) gradient and reveal that the temperature compensation for the Bcd gradient is stronger in the later developmental stage.

developmental biology↗