Biology subjects

Iqbal, M.

Publications and source records attributed to Iqbal, M..

51 records · Page 3Linked to original sources

bioRxiv2022

The origin of internal genes contributes to the replication and transmission fitness of H7N9 avian influenza virus

H9N2 avian influenza viruses (AIVs) have donated internal gene segments during the emergence of zoonotic AIVs, including H7N9. We used reverse genetics to generate three reassortant viruses (2:6 H7N9) which contained the Haemagglutinin and Neuraminidase from Anhui/13 (H7N9) and the six internal gene segments from H9N2 AIVs of G1-like or BJ94-like lineages enzootic in different geographic regions in Asia. Infection of chickens with the 2:6 H7N9 containing internal gene segments from G1-like H9N2 conferred attenuation in vivo, with lower shedding and reduced transmission to contact chickens. However, possession of BJ94-like H9N2 internal gene segments resulted in more rapid transmission and significantly elevated cloacal shedding compared to the parental Anhui/13 H7N9. In vitro analysis also showed that the 2:6 H7N9 having BJ94-like internal genes had significantly increased replication compared to the Anhui/13 H7N9 in chicken cells. In vivo co-infection experiments followed, where chickens were co-infected with pairs of Anhui/13 H7N9 and one of each of the three 2:6 H7N9 reassortants. During ensuing transmission events, the Anhui/13 H7N9 virus outcompeted 2:6 H7N9 with internal gene segments of BJ94-like or G1-like H9N2 viruses. Co-infection did lead to the emergence of novel reassortant genotypes that were transmitted to contact chickens. Some of the reassortant viruses had a greater replication in chicken and human cells compared to the progenitors. We demonstrated that the internal gene cassette determines the transmission fitness of H7N9 viruses in chickens and the reassortment events can generate novel H7N9 genotypes with increased virulence in chickens and enhanced zoonotic potential. ImportanceH9N2 avian influenza viruses (AIVs) are enzootic in poultry in different geographical regions. The internal genes of these viruses can be exchanged with other zoonotic AIVs, most notably the China-origin H7N9 that can give rise to new virus genotypes with increased veterinary, economic and public health threats to both poultry and humans. We investigated the propensity of the internal genes of H9N2 viruses (G1 or BJ94) in the generation of novel reassortant H7N9 AIVs. We observed that the internal genes of H7N9 which were derivative of BJ94-like H9N2 virus have a fitness advantage compared to those from the G1-like H9N2 viruses for efficient transmission among chickens. We also observed the generation of novel reassortant viruses during chicken transmission which infected and replicated efficiently in human cells. Therefore, such emergent reassortant genotypes may pose an elevated zoonotic threat.

microbiology↗

bioRxiv2021

HNF4A is required to specify glucocorticoid action in the liver

The glucocorticoid receptor (GR) is a nuclear hormone receptor critical to the regulation of energy metabolism and the inflammatory response. The actions of GR are highly dependent on cell type and environmental context. Here, we demonstrate the necessity for liver lineage-determining factor hepatocyte nuclear factor 4A (HNF4A) in defining liver-specificity of GR action. In normal mouse liver, the HNF4 motif lies adjacent to the glucocorticoid response element (GRE) at GR binding sites found within regions of open chromatin. In the absence of HNF4A, the liver GR cistrome is remodelled, with both loss and gain of GR recruitment evident. Lost sites are characterised by HNF4 motifs and weak GRE motifs. Gained sites are characterised by strong GRE motifs, and typically show GR recruitment in non-liver tissues. The functional importance of these HNF4A-regulated GR sites is further demonstrated by evidence of an altered transcriptional response to glucocorticoid treatment in the Hnf4a-null liver.

molecular biology↗

bioRxiv2021

Co-infection of chickens with H9N2 and H7N9 avian influenza viruses leads to emergence of reassortant H9N9 virus with increased fitness for poultry and enhanced zoonotic potential

An H7N9 low pathogenicity avian influenza virus (LPAIV) emerged through genetic reassortment between H9N2 and other LPAIVs circulating in birds in China. This virus causes inapparent clinical disease in chickens, but zoonotic transmission results in severe and fatal disease in humans. We evaluated the consequences of reassortment between the H7N9 and the contemporary H9N2 viruses of G1 lineage that are enzootic in poultry across the Indian sub-continent and the Middle East. Co-infection of chickens with these viruses resulted in emergence of novel reassortant H9N9 viruses carrying genes derived from both H9N2 and H7N9 viruses. These reassortant H9N9 viruses showed significantly increased replication fitness, enhanced pathogenicity in chicken embryos and the potential to transmit via contact among ferrets. Our study highlights that the co-circulation of H7N9 and H9N2 viruses could represent a threat for the generation of novel reassortant viruses with greater virulence in poultry and an increased zoonotic potential. O_FIG O_LINKSMALLFIG WIDTH=197 HEIGHT=200 SRC="FIGDIR/small/438444v1_ufig1.gif" ALT="Figure 1"> View larger version (96K): org.highwire.dtl.DTLVardef@1f425cborg.highwire.dtl.DTLVardef@1dd3ba2org.highwire.dtl.DTLVardef@1762348org.highwire.dtl.DTLVardef@1064cb7_HPS_FORMAT_FIGEXP M_FIG Graphical Abstract C_FIG In BriefH9N2 viruses have a high propensity to reassort with other avian influenza viruses. We found that co-infection of chickens with H9N2 and H7N9 led to the emergence of reassortant viruses including the H9N9 subtype. Some reassortant H9N9 viruses exhibited increased replication fitness, increased pathogenicity in the chicken embryo, greater avidity for human and avian cell receptors, lower pH fusion and contact-transmission to ferrets. This study demonstrated the ability of viruses that already exist in nature to exchange genetic material, highlighting the potential emergence of viruses from these subtypes with increased zoonotic potential. There are nine H9 influenza A subtypes carrying different neuraminidase (NA) genes, including H9N9 viruses, while they are not common they do exist in nature as wildtypes (CDC). HighlightsO_LICo-infection of chickens with H7N9 and H9N2 led to emergence of reassortant H9N9 viruses C_LIO_LIReassortant H9N9 viruses had an increased replication rate in avian and human cells C_LIO_LIReassortant H9N9 viruses had a lower pH fusion and significantly higher receptor binding to 2,3 sialoglycans C_LIO_LIReassortant H9N9 replicated in ferrets at similar levels compared to H7N9 and transmitted via direct contact C_LIO_LIFerrets exposed to reassortant H9N9 by aerosol contact were also found to be seropositive C_LIO_LIExperimental simulation of events that may occur naturally with circulating viruses has demonstrated the risk of emergence of viruses with increased zoonotic potential. C_LI

microbiology↗

bioRxiv2021

Immunogenicity and Protective Efficacy of an Intranasal Live-attenuated Vaccine Against SARS-CoV-2 in Preclinical Animal Models

The global deployment of an effective and safe vaccine is currently a public health priority to curtail the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we evaluated a Newcastle disease virus (NDV)-based intranasal vectored-vaccine in mice and hamsters for its immunogenicity, safety and protective efficacy in challenge studies with SARS-CoV-2. The recombinant (r)NDV-S vaccine expressing spike (S) protein of SARS-CoV-2 administrated via intranasal route in mice induced high levels of SARS-CoV-2-specific neutralizing immunoglobulin A (IgA) and IgG2a antibodies and T cell-mediated immunity. Hamsters vaccinated with two doses of vaccine showed complete protection from clinical disease including lung infection, inflammation, and pathological lesions after SARS-CoV-2 challenge. Importantly, a single or double dose of intranasal rNDV-S vaccine completely blocked SARS-CoV-2 shedding in nasal turbinate and lungs within 4 days of vaccine administration in hamsters. Taken together, intranasal administration of rNDV-S has the potential to control infection at the site of inoculation, which should prevent both the clinical disease and transmission to halt the spread of the COVID-19 pandemic.

immunology↗

bioRxiv2020

An assessment of efficacy of Iodine complex (Renessans) against SARS-CoV-2 in non-human primates (Rhesus macaque)

Renessans is an iodine complex which has proven in vitro antiviral activity including Anti-SARS-CoV-2 activity. The present study was designed to determine its efficacy against SARS-CoV-2 in monkeys (Rhesus macaque). A total of 14 monkeys were divided into four groups: A) Prophylactic group (n=03), (B) Treatment group (n=03), (C) infection control group (n=04) and (D) negative control group (n=04) and were housed in BSL-3 Animal facility while group D was housed at another animal house. Group A was administered with Renessans @ 2.85 mg/7 kg from 5 days prior to the infection to 08 days post infections (DPI). Group B was administered with Renessans from 03-08 DPI @ 2.85 mg/7 kg. Group C was administered with WIF only. The infection @ 2 x 106 TCID of SARS-CoV-2 was given to all group monkeys through intranasal and oral route under anesthesia. Nasal swab samples (at different times) and fecal matter on daily basis were collected for the detection of SARS-CoV-2 through real-time quantitative PCR. Three monkeys (one from each of group A, B and C) were euthanized at 07 DPI to determine the gross pathological lesions and SARS-CoV-2 detection from internal tissues. Nasal swabs from all the monkeys from group A, B and C were positive for SARS-CoV-2 at 02 and 07 DPI (Day 05 of treatment). At 14 DPI, all (100%) nasal swabs from group A were negative for SARS-CoV-2 while 50% and 100% were positive from group B and C, respectively. At 21 DPI, monkeys from group B were negative and all in group C were still positive for SARS-CoV-2. Similarly, fecal matter of monkeys in group A and B was returned negative in significantly lesser time as compared to monkeys from infection control group. Based on these research findings it is concluded that the Renessans has in-vivo SARS-CoV-2 activity and may result in early clearance of SARS-CoV-2. Therefore, a clinical trial of the drug in COVID-19 patients may reveal its anti-COVID-19 potential.

microbiology↗

bioRxiv2020

Adipocyte REVERBα dictates adipose tissue expansion during obesity

The circadian clock component REVERB is considered a dominant regulator of lipid metabolism, with global Reverb deletion driving dysregulation of white adipose tissue (WAT) lipogenesis and obesity. However, a similar phenotype is not observed under adipocyte-selective deletion (ReverbFlox2-6AdipoCre), and transcriptional profiling demonstrates that, under basal conditions, direct targets of REVERB regulation are limited, and include the circadian clock and collagen dynamics. Under high-fat diet (HFD) feeding, ReverbFlox2-6AdipoCre mice do manifest profound obesity, yet without the accompanying WAT inflammation and fibrosis exhibited by controls. Integration of the WAT REVERB cistrome with differential gene expression reveals broad control of metabolic processes by REVERB which is unmasked in the obese state. Adipocyte REVERB does not drive an anticipatory daily rhythm in WAT lipogenesis, but rather modulates WAT activity in response to alterations in metabolic state. Importantly, REVERB action in adipocytes is critical to the development of obesity-related WAT pathology and insulin resistance.

physiology↗

bioRxiv2020

Contribution of segment 3 to the acquisition of virulence in contemporary H9N2 avian influenza viruses

H9N2 avian influenza viruses circulate in poultry throughout much of Asia, the Middle East and Africa. These viruses cause huge economic damage to poultry production systems and pose a zoonotic threat both in their own right as well as in the generation of novel zoonotic viruses, for example H7N9. In recent years it has been observed that H9N2 viruses have further adapted to poultry, becoming more highly transmissible and causing higher morbidity and mortality. Here, we investigate the molecular basis for this increased virulence, comparing a virus from the 1990s and a contemporary field strain. The modern virus replicated to higher titres in various systems and this difference mapped to a single amino acid polymorphism at position 26 of the endonuclease domain shared by the PA and PA-X proteins. This change was responsible for the virulent phenotype and extended tissue tropism seen in chickens. Although the PA K26E change correlated with increased host cell shutoff activity of the PA-X protein in vitro, it could not be overridden by frameshift site mutations that block PA-X expression and therefore increased PA-X activity could not explain the differences in replication phenotype. Instead, this indicates these differences are due to subtle effects on PA function. This work gives insight into the ongoing evolution and poultry adaptation of H9N2 and other avian influenza viruses and helps us understand the soaring morbidity and mortality rates in the field, as well as rapidly expanding geographical range seen in these viruses. Author SummaryAvian influenza viruses, such as H9N2, cause huge economic damage to poultry production worldwide and are additionally considered potential pandemic threats. Understanding how these viruses evolve in their natural hosts is key to effective control strategies. In the Middle East and South Asia an older H9N2 virus strain has been replaced by a new reassortant strain with greater fitness. Here we take representative viruses and investigate the genetic basis for this fitness. A single mutation in the virus was responsible for greater fitness, enabling high growth of the contemporary H9N2 virus in cells, as well as in chickens. The genetic mutation that modulates this change is within the viral PA protein, a part of the virus polymerase gene that contributes in viral replication as well as contribute in the virus accessory functions - however we find that the fitness effect is specifically due to changes in the protein polymerase activity.

microbiology↗

bioRxiv2020

PA-X is an avian virulence factor in H9N2 avian influenza virus

Influenza A viruses encode several accessory proteins that have host- and strain-specific effects on virulence and replication. The accessory protein PA-X is expressed due to a ribosomal frameshift during translation of the PA gene. Depending on the particular combination of virus strain and host species, PA-X has been described as either acting to either reduce or increase virulence and/or virus replication. In this study, we set out to investigate the role PA-X plays in H9N2 avian influenza viruses, focussing particularly on the natural avian host, chickens. We found H9N2 PA-X induced robust host shutoff in both mammalian and avian cells and increased replication in mammalian, but not avian cells. We further showed that PA-X affected embryonic lethality in ovo and led to more rapid viral shedding and widespread organ dissemination in vivo in chickens. Overall, we conclude PA-X may act as a virulence factor for H9N2 viruses in chickens, allowing faster replication and wider organ tropism.

microbiology↗

bioRxiv2020

Genetic determinants of receptor-binding preference and zoonotic potential of H9N2 avian influenza viruses

Receptor recognition and binding is the first step of viral infection and a key determinant of host specificity. The inability of avian influenza viruses to effectively bind human-like sialylated receptors is a major impediment to their efficient transmission in humans and pandemic capacity. Influenza H9N2 viruses are endemic in poultry across Asia and parts of Africa where they occasionally infect humans and are therefore considered viruses with zoonotic potential. We previously described H9N2 viruses, including several isolated from human zoonotic cases, showing a preference for human-like receptors. Here we take a mutagenesis approach, making viruses with single or multiple substitutions in H9 haemagglutinin to determine the genetic basis of preferences for alternative avian receptors and for human-like receptors. We describe amino acid motifs at positions 190, 226 and 227 that play a major role in determining receptor specificity, and several other residues such as 159, 188, 193, 196, 198 and 225 play a smaller role. Furthermore, we show changes at residues 135, 137, 147, 157, 158, 184, 188, and 192 can also modulate virus receptor avidity and that substitutions that increased or decreased the net positive charge around the haemagglutinin receptor-binding site show increases and decreases in avidity, respectively. The motifs we identify as increasing preference for the human-receptor will help guide future H9N2 surveillance efforts and facilitate our understanding of the emergence of influenza viruses with high zoonotic potential. Author SummaryAs of 2020, over 60 infections of humans by H9N2 influenza viruses have been recorded in countries were the virus is endemic. Avian-like cellular receptors are the primary target for these viruses. However, given that human infections have been detected on an almost monthly basis since 2015, there may be a capacity for H9N2 viruses to evolve and gain the ability to target human-like cellular receptors. Here we identify molecular signatures that can cause viruses to bind human-like receptors, and we identify the molecular basis for the distinctive preference for sulphated receptors displayed by the majority of recent H9N2 viruses. This work will help guide future surveillance by providing markers that signify the emergence of viruses with enhanced zoonotic potential as well as improving understanding the basis of influenza virus receptor-binding.

microbiology↗

bioRxiv2020

Competitive approach of invasive cocklebur (Xanthium strumarium) with native weed species diversity in Northeast China

Xanthium strumarium is yearly weed local to North America and is presently an obtrusive species. The intrusive weed can contend with local decent variety may turn into a hazardous weed for the agrarian profitability and rangeland biological systems. The present examination researched the challenge of intrusive and local weed populaces inside two straight out variables in matched quadratic rings (treatment/invasive with control/non-invasive). The present investigation was led at four unique areas of northeast China to discover competition of Xanthium strumarium on 40 paired matched vegetations in same condition and living space conditions. The number of species (NOS) occurred in quadratic ring; abundance (A); Simpsons Diversity Index (SDI); Margalefs Richness Index (MRI) compared between invasive and non-invasive quadrates by t-test was recorded significant (P<0.05) suggestion of competitions between plant communities. The abundance in communities decreased significantly in invasive compared to non-invasive quadrate gave an indication about low productivity of plant species due to Xanthium strumarium. Rarefaction bend with respect to coefficient of determination (R2) explored in the overviewed network (0.86) proposed that there is a solid positive polynomial connection between various weed families. Greatest difference list (87.06%) recorded in Huailai province followed by Yangyuan (44.43%), Zhangjiakou (40.13%) and at Fushun (29.02%). Significant (P<0.05) maximum global R demonstrated high species decent variety was found in Huailai area (0.943) trailed by Zhangjiakou. Significant (P<0.05) density of native weed was recorded in non-invasive quadrate which was comparable to the invasive quadrate. Finally invasive Xanthium strumarium compete with native weeds diversity created significant threat to the natural diversity. Most extreme thickness of weed species gave cautioning that the predominant edaphic and natural states of the uneven regions are profoundly favorable for the dispersion and development of the weed in future.

ecology↗

bioRxiv2020

Phytochemical screening, GC-MS profiling of invasive cocklebur (Xanthium strumarium)-insect-pathogen interaction and simulated volatile chemical signaling at Northeast China

Invasive cocklebur (Xanthium strumarium) is characterized by its excellent genetic and ecological plasticity, ability to spread in agriculture crops. There is a dire need to locate useful management strategies to control this invasive weed at diversified latitudinal gradients. In ecology, there is weak evidence that the damage caused by the natural enemy varies with latitudes. Therefore, we investigated this evidence with the help of transect quadratic ecological sampling method which was conducted randomly at ten different sites of Northeast China. Overall, significantly high infestation of gall-forming insect (Epiblema strenuana) was observed on Xanthium leaves (21.16%) at 41.51279{degrees}N, followed by 40.2241{degrees}N latitude. Similarly, there was a significantly high abundance of Epiblema infestation (7.3) with high damage (3.88%) at 41.51279{degrees}N and 40.12749{degrees}N latitude. Likewise, the fungal abundance (5.6) of rust i.e. Puccinia xanthii (presenting 16.23% attack) was dominated significantly at 41.51279{degrees}N. Hence, high pathogen infection rate (8.97%) was detected at 40.2241{degrees}N. On the other hand growth parameters, i.e. plant height (cm), stem diameter (mm) vary with latitude and longitudinal trends. In our experiment, of plant natural enemy interaction provides the evidence-based indication the Epiblema abundance, was diversified at 41.51279{degrees}N, and P. xanthii infection was most frequent at 40.22411{degrees}N latitudes. This study provides an evidence-based indication that natural enemy pressure varies with latitude, however this investigations gave valuable information that insect and phytopathological fungus having biological control potential against Xanthium strumarium invasive weed. Secondly, phytochemical qualitative and chemical signaling through Gas Chromatography-mass spectrometry (GC-MS) executed the presence of flavonoids, phenols, saponins, alkaloids, terpenoids, nitrogen (N), sulpher (S), silicon (Si) containing compounds in both treated and controlled leaves that defend against Puccinia xanthii. Fascinatingly, all X. strumarium populations collected from different latitudes possess similar compositions. In interaction mechanism, plant known to omit volatile organic compounds in response to attack of natural herbivores. The leave chemical profiling suggested that the influence of fungus attack on invasive weed brought different changes in chemical infrastructure of leave and these chemicals also play a vital role in the food web. After attack of these biological control agents, plants exhibits passionate compound reprogramming within the leaf naturally that act upon in defense systems. Author summaryO_LIThe study was conducted to observe the environmental impact on the trend of insect, invasive weed and pathogens. C_LIO_LIThere was a significant dominance of gall-forming insect on invasive Xanthium weed at all locations. C_LIO_LIPuccinia xanthii infected more than 16% plantation C_LIO_LIPlant growth had significant variation at various longitudes and latitudes. C_LIO_LIThe abundance of insect was positively linked with different environmental factors and Xanthium plant. C_LIO_LIThe results of GC-MS suggested that Puccinia xanthii infected (treatment) leaves covered maximum area (%) compared to control treatments due to breakdown of the chemical compounds that proved our hypotheses that volatile organic compounds altered infrastructures of the leave chemistry that led to activeness of plant defensive chemicals resulted invasion success. C_LI

biochemistry↗

bioRxiv2018

Article The Genotype Diversity within the H5N8 Influenza A Subtype

The H5N8 influenza subtype has been involved in the global spread of the Guangdong variant of the H5 hemagglutinin. The sequence data from all of the complete genomes from the H5N8 subtype was used to analyse the genotype diversity. Clustering analysis was used to assign lineages to each of the segments where different lineages were present. The results show that there have been multiple reassortment events both within the Guangdong and non-Guangdong H5 hemagglutinin containing variants. The Guangdong H5 variants can be subdivided further into two sub-lineages 2.3.4.4.A and 2.3.4.4.B that have undergone reassortment in both the far east and the United States.

evolutionary biology↗

bioRxiv2018

ZIC3 controls the transition from naïve to primed pluripotency.

Embryonic stem cells (ESCs) are pluripotent in nature, meaning that they have the capacity to differentiate into any cell in the body. However, to do so they must transition through a series of intermediate cell states before becoming terminally differentiated. A lot is known about how ESCs maintain their pluripotent state but comparatively less about how they exit this state and begin the transition towards differentiated cells. Here we investigated the earliest events in this transition by determining the changes in the open chromatin landscape as naive mouse ESCs transition to epiblast-like cells (EpiLCs). Motif enrichment analysis of the newly opening regions coupled with expression analysis identified ZIC3 as a potential regulator of this cell fate transition. Chromatin binding and genome-wide transcriptional profiling confirmed ZIC3 as an important regulatory transcription factor and among its targets are genes encoding a number of transcription factors. Among these is GRHL2 which acts through enhancer switching to maintain the expression of a subset of genes from the ESC state. Our data therefore place ZIC3 at the top of a cascade of transcriptional regulators and provide an important advance in our understanding of the regulatory factors governing the earliest steps in ESC differentiation.\n\nHighlightsO_LIThe transcription factor ZIC3 drives gene expression changes in the ESC to EpiLC transition.\nC_LIO_LIExtensive changes occur in the open chromatin landscape as ESCs progress to EpiLCs.\nC_LIO_LIZIC3 activates the expression of a network of transcription factors.\nC_LIO_LIZIC3 activated genes in EpiLCs are upregulated in the post-implantation epiblast.\nC_LI

developmental biology↗

bioRxiv2018

The molecular basis of antigenic variation among A(H9N2) avian influenza viruses

Avian influenza A(H9N2) viruses are an increasing threat to global poultry production and, through zoonotic infection, to human health where they are considered viruses with pandemic potential. Vaccination of poultry is a key element of disease control in endemic countries, but vaccine effectiveness is persistently challenged by the emergence of antigenic variants. Here we employed a combination of techniques to investigate the genetic basis of H9N2 antigenic variability and evaluate the role of different molecular mechanisms of immune escape. We systematically tested the influence of published H9N2 monoclonal antibody escape mutants on chicken antisera binding, determining that many have no significant effect. Substitutions introducing additional glycosylation sites were a notable exception, though these are relatively rare among circulating viruses. To identify substitutions responsible for antigenic variation in circulating viruses, we performed an integrated meta-analysis of all published H9 haemagglutinin sequences and antigenic data. We validated this statistical analysis experimentally and allocated several new residues to H9N2 antigenic sites providing molecular markers that will help explain vaccine breakdown in the field and inform vaccine selection decisions. We find evidence for the importance of alternative mechanisms of immune escape, beyond simple modulation of epitope structure, with substitutions increasing glycosylation or receptor-binding avidity exhibiting the largest impacts on chicken antisera binding. Of these, meta-analysis indicates avidity regulation to be more relevant to the evolution of circulating viruses, suggesting that a specific focus on avidity regulation is required to fully understand the molecular basis of immune escape by influenza, and potentially other viruses.

microbiology↗

bioRxiv2017

Reconstructing Promoter Activity From Lux Bioluminescent Reporters

The bacterial Lux system is used as a gene expression reporter. It is fast, sensitive and non-destructive, enabling high frequency measurements. Originally developed for bacterial cells, it has been adapted for eukaryotic cells, and can be used for whole cell biosensors, or in real time with live animals without the need for slaughter. However, correct interpretation of bioluminescent data is limited: the bioluminescence is different from gene expression because of nonlinear molecular and enzyme dynamics of the Lux system. We have developed a modelling approach that, for the first time, allows users of Lux assays to infer gene transcription levels from the light output. We show examples where a decrease in bioluminescence would be better interpreted as a switching off of the promoter, or where an increase in bioluminescence would be better interpreted as a longer period of gene expression. This approach could benefit all users of Lux technology.

bioinformatics↗