Biology subjects

Asgari, S.

Publications and source records attributed to Asgari, S..

At least 19 recordsLinked to original sources

bioRxiv2026

Rapid RPA-CRISPR/Cas12a detection of Vibrio coralliilyticus for coral aquaculture disease surveillance

Coral aquaculture is expanding globally to support both the ornamental aquarium trade and reef-restoration initiatives, yet disease outbreaks remain a threat to production, causing potential substantial coral mortality and economic losses. Effective disease management requires early pathogen detection; however, conventional molecular diagnostics are labor-intensive and poorly suited to time-sensitive aquaculture operations. Here, we developed a rapid diagnostic assay for the coral pathogen Vibrio coralliilyticus by implementing recombinase polymerase amplification (RPA) with Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas12a-based fluorescent signaling for sensitive and specific detection. The assay was optimized and validated against DNA from seven V. coralliilyticus strains and seven non-target Vibrio species, demonstrating high specificity and a detection limit <10 target copies per reaction within 30 minutes following DNA extraction. Performance of the assay was further evaluated using water from flow-through aquaria containing healthy and diseased Acropora tersa colonies, and results independently validated using droplet digital PCR (ddPCR). Although RPA-CRISPR/Cas12a consistently detected V. coralliilyticus across the tanks holding both healthy and diseased corals, ddPCR indicated substantially higher pathogen abundance in diseased tanks, suggesting that pathogen load rather than the presence alone is a more reliable indicator of disease risk. Incorporating rapid semi-quantification of pathogen abundance in future assay development could therefore improve disease prediction and management. This study demonstrates the potential of CRISPR-based diagnostics as a fast, sensitive, and field deployable tool for routine coral aquaculture biosecurity, enabling earlier intervention and more effective mitigation of disease outbreaks.

molecular biology↗

bioRxiv2026

The vacuolar tauopathy-associated mutation D395G confers redox sensitivity to p97/VCP

The multifunctional AAA+ ATPase p97/VCP is a pivotal regulator of cellular proteostasis, extracting polyubiquitinated substrates from protein complexes or organelle membranes for proteasomal degradation. Mutations in p97 are linked to a broad spectrum of neurodegenerative disorders, including multisystem proteinopathy and amyotrophic lateral sclerosis. Here, we provide insights into the basis of dysfunction in p97D395G, implicated in vacuolar tauopathy, using an integrated structural approach. The mutation destabilizes the interaction network in the transient ADP.Pi state previously identified in p97WT and alters the dynamics of the linker between the tandem ATPase domains, resulting in decreased ATPase activity. We further demonstrate that the D395G mutation sensitizes p97 to oxidative stress by enhancing C522 oxidation, thereby perturbing nucleotide binding in D2, and define the functional basis of this oxidative inactivation of p97. These findings reveal redox control as a key regulatory layer of the p97 ATPase cycle and provide a mechanistic framework for how oxidative stress contributes to p97-associated neurodegeneration.

molecular biology↗

bioRxiv2025

Viral infections shape inter-individual immune variability

Viral infections can shape adaptive immunity, but whether they also influence innate immune responses later in life remains incompletely characterized. Here, we profiled serum from 12 healthy adults using VirScan, a high-throughput serological assay that infers prior viral exposures by mapping antiviral antibody reactivity across a broad range of viral epitopes. We paired this with ex vivo stimulation of TLR3 and TLR7/8 antiviral pathways and tested whether post-stimulation inflammatory responses are associated with prior viral exposures. At the antibody level, we observed consistent immunodominance at the protein level across individuals, alongside substantial variability at the epitope level. At the functional level, prior exposure to HSV-1, HSV-2, and norovirus was associated with differential production of CCL4, MCP-2, and TNF following TLR7/8 stimulation, respectively. This pilot study establishes a framework for integrating broad viral serology with functional immune profiling to investigate links between lifetime exposures and immune variability. Our results suggest that past viral infections, including acute infections, can contribute to variation in innate immune responses later in life. Larger studies will be required to validate these associations, establish causality, and determine the underlying mechanisms.

immunology↗

bioRxiv2023

Aedes aegypti gut transcriptomes respond differently to microbiome transplants from field-caught or laboratory-reared mosquitoes.

The mosquito microbiome is critical for host development and plays a major role in many aspects of mosquito biology. While the microbiome is commonly dominated by a small number of genera, there is considerable variation in composition among mosquito species, life stages, and geography. How the host controls and is affected by this variation is unclear. Using microbiome transplant experiments, we asked whether there were differences in transcriptional responses when mosquitoes of different species were used as microbiome donors. We used microbiomes from four different donor species spanning the phylogenetic breadth of the Culicidae, collected either from the laboratory or field. We found that when recipients received a microbiome from a donor reared in the laboratory, the response was remarkably similar regardless of donor species. However, when the donor had been collected from the field, far more genes were differentially expressed. We also found that while the transplant procedure did have some effect on the host transcriptome, this is likely to have had a limited effect on mosquito fitness. Overall, our results highlight the possibility that variation in mosquito microbiome communities are associated with variability in host-microbiome interactions and further demonstrate the utility of the microbiome transplantation technique.

microbiology↗

bioRxiv2023

High-dimensional phenotyping to define the genetic basis of cellular morphology

The morphology of cells is dynamic and mediated by genetic and environmental factors. Characterizing how genetic variation impacts cell morphology can provide an important link between disease association and cellular function. Here, we combined genomic and high-content imaging approaches on iPSCs from 297 unique donors to investigate the relationship between genetic variants and cellular morphology to map what we term cell morphological quantitative trait loci (cmQTLs). We identified novel associations between rare protein altering variants in WASF2, TSPAN15, and PRLR with several morphological traits related to cell shape, nucleic granularity, and mitochondrial distribution. Knockdown of these genes by CRISPRi confirmed their role in cell morphology. Analysis of common variants yielded one significant association and nominated over 300 variants with suggestive evidence (P<10-6) of association with one or more morphology traits. Our results showed that, similar to other molecular phenotypes, morphological profiling can yield insight about the function of genes and variants.

genomics↗

bioRxiv2022

Analysis of Aedes aegypti microRNAs in response to Wolbachia wAlbB infection and their potential role in mosquito longevity

The mosquito Aedes aegypti is the primary vector of a range of medically important viruses including dengue, Zika, West Nile, yellow fever, and chikungunya viruses. The endosymbiotic bacterium Wolbachia pipientis wAlbB strain is a promising biocontrol agent for blocking viral transmission by Ae. aegypti. To predict the long-term efficacy of field applications, a thorough understanding of the interactions between symbiont, host, and pathogen is required. Wolbachia influence host physiology in a variety of ways including reproduction, immunity, metabolism, and longevity. MicroRNAs (miRNAs) are highly conserved small non-coding RNAs that regulate gene expression in eukaryotes and viruses. A number of miRNAs are known to regulate biological processes in Drosophila and mosquitoes, including facilitating Wolbachia maintenance. We generated the first chromosomal map of Ae. aegypti miRNAs, and compared miRNA expression profiles between a wAlbB-transinfected Ae. aegypti mosquito line and a tetracycline cleared derivative, using deep small RNA-sequencing. We found limited modulation of miRNAs in response to wAlbB infection. Several miRNAs were modulated in response to age, some of which showed greater upregulation in wAlbB-infected mosquitos than in tetracycline cleared ones. By selectively inhibiting some differentially expressed miRNAs, we identified miR-2946-3p and miR-317-3p as effecting mosquito longevity. ImportanceWolbachia is an endosymbiotic bacterium found in about 65% of insect species. It is mostly known for reproductive manipulations of the host, and also blocking replication of positive sense RNA viruses. Transinfection of Wolbachia into Aedes aegypti mosquitoes, which transmit a variety of arboviruses, including dengue virus, has provided a novel biological approach in reducing transmission of arboviruses. To gain a better understanding of Wolbachia-mosquito interactions, we investigated the impact of Wolbachia on the microRNA profile of Ae. aegypti mosquitoes. We produced the first chromosome-level map of Ae. Aegypti miRNAs. We found modulation of microRNAs in mosquitoes due to age, with two miRNAs, 317-3p and 2946-3p, showing significant increase with age. Inhibition of 317-3p and 2946-3p led to reduced mosquito life span in wAlbB-infected mosquitoes. The outcomes provide insights into underlying molecular mechanisms involved in Wolbachia-host interactions.

microbiology↗

bioRxiv2021

Modeling memory T cell states at single-cell resolution identifies in vivo state-dependence of eQTLs influencing disease

Many non-coding genetic variants cause disease by modulating gene expression. However, identifying these expression quantitative trait loci (eQTLs) is complicated by gene-regulation differences between cell states. T cells, for example, have fluid, multifaceted functional states in vivo that cannot be modeled in eQTL studies that aggregate cells. Here, we modeled T cell states and eQTLs at single-cell resolution. Using >500,000 resting memory T cells from 259 Peruvians, we found over one-third of the 6,511 cis-eQTLs had state-dependent effects. By integrating single-cell RNA and surface protein measurements, we defined continuous cell states that explained more eQTL variation than discrete states like CD4+ or CD8+ T cells and could have opposing effects on independent eQTL variants in a locus. Autoimmune variants were enriched in cell-state-dependent eQTLs, such as a rheumatoid-arthritis variant near ORMDL3 strongest in cytotoxic CD8+ T cells. These results argue that fine-grained cell state context is crucial to understanding disease-associated eQTLs.

genetics↗

bioRxiv2021

A sex-specific evolutionary interaction between ADCY9 and CETP

Pharmacogenomic studies have revealed associations between rs1967309 in the adenylyl cyclase type 9 (ADCY9) gene and clinical responses to the cholesteryl ester transfer protein (CETP) modulator dalcetrapib, however, the mechanism behind this interaction is still unknown. Here, we characterized selective signals at the locus associated with the pharmacogenomic response in human populations and we show that rs1967309 region exhibits signatures of positive selection in several human populations. Furthermore, we identified a variant in CETP, rs158477, which is in long-range linkage disequilibrium with rs1967309 in the Peruvian population. The signal is mainly seen in males, a sex-specific result that is replicated in the LIMAA cohort of over 3,400 Peruvians. Analyses of RNA-seq data further suggest an epistatic interaction on CETP expression levels between the two SNPs in multiple tissues, which also differs between males and females. We also detected interaction effects of the two SNPs with sex on cardiovascular phenotypes in the UK Biobank, in line with the sex-specific genotype associations found in Peruvians at these loci. We propose that ADCY9 and CETP coevolved during recent human evolution due to sex-specific selection, which points towards a biological link between dalcetrapibs pharmacogene ADCY9 and its therapeutic target CETP.

genetics↗

bioRxiv2020

Multimodal memory T cell profiling identifies a reduction in a polyfunctional Th17 state associated with tuberculosis progression

Mycobacterium tuberculosis (M.tb) results in 10 million active tuberculosis (TB) cases and 1.5 million deaths each year1, making it the worlds leading infectious cause of death2. Infection leads to either an asymptomatic latent state or TB disease. Memory T cells have been implicated in TB disease progression, but the specific cell states involved have not yet been delineated because of the limited scope of traditional profiling strategies. Furthermore, immune activation during infection confounds underlying differences in T cell state distributions that influence risk of progression. Here, we used a multimodal single-cell approach to integrate measurements of transcripts and 30 functionally relevant surface proteins to comprehensively define the memory T cell landscape at steady state (i.e., outside of active infection). We profiled 500,000 memory T cells from 259 Peruvians > 4.7 years after they had either latent M.tb infection or active disease and defined 31 distinct memory T cell states, including a CD4+CD26+CD161+CCR6+ effector memory state that was significantly reduced in patients who had developed active TB (OR = 0.80, 95% CI: 0.73-0.87, p = 1.21 x 10-6). This state was also polyfunctional; in ex vivo stimulation, it was enriched for IL-17 and IL-22 production, consistent with a Th17-skewed phenotype, but also had more capacity to produce IFN{gamma} than other CD161+CCR6+ Th17 cells. Additionally, in progressors, IL-17 and IL-22 production in this cell state was significantly lower than in non-progressors. Reduced abundance and function of this state may be an important factor in failure to control M.tb infection.

immunology↗

bioRxiv2019

Transinfection of buffalo flies (Haematobia exigua) with Wolbachia and effect on host biology

A widespread insect endosymbiont Wolbachia is currently of much interest for use in novel strategies for the control of insect pests and blocking transmission of insect-vectored diseases. Wolbachia-induced effects can vary from beneficial to detrimental depending on host biology and the genetic background of the infecting strains. As a first step towards investigating the potential of Wolbachia for use in the biocontrol of buffalo flies (BF), embryos, pupae, and adult female BF were injected with three different Wolbachia strains (wAlbB, wMel and wMelPop). BF eggs were not easily injected because of their tough outer chorion and embryos were frequently damaged resulting in less than 1% hatch rate of microinjected eggs. No Wolbachia infection was recorded in flies successfully reared from injected eggs. Adult and pupal injection gave a much higher survival rate and resulted in somatic infection and germinal tissue infection in surviving flies with transmission to the succeeding generations on a number of occasions. Investigations of infection dynamics in flies from injected pupae confirmed that Wolbachia were increasing in numbers in BF somatic tissues and ovarian infections were confirmed with wMel and wMelPop in some instances, though not with wAlbB. Measurement of fitness traits indicated reduced longevity, decreased and delayed adult emergence, and reduced fecundity in Wolbachia-infected flies in comparison to mock-injected flies. Furthermore, fitness effects varied according to the Wolbachia strain injected with most marked reductions seen in the wMelPop-injected flies and least severe effects seen with the wAlbB strain.

microbiology↗

bioRxiv2019

Wolbachia promote successful sex with siblings

Wolbachia are intracellular -proteobacteria that have a wide distribution among various arthropods and nematodes. They affect the host reproduction favoring their maternal transmission, which sets up a potential conflict in inbreeding situations when the host avoids sexual reproduction preventing inbreeding depression, while Wolbachia pushes it. In this study, we used the wasp Habrobracon hebetor to test the hypothesis that Wolbachia modulate inbreeding avoidance behaviour and promote sib mating. To test this, we first cured wasps of Wolbachia using tetracycline treatment and produced infected and uninfected isolines. Then, we paired the uninfected and infected females with sibling (inbred) and non-sibling (outbred) males in choice and non-choice experiments. Our results showed no obvious precopulatory inbreeding avoidance in this wasp as brother-sister mating rates (in both choice and nonchoice experiments) were not significantly different form non-sibling pairs, regardless of Wolbachia infection. However, our results indicated that H. hebetor shows a strong postcopulatory inbreeding avoidance behaviour that results in a low fertilization rate of uninfected siblings and therefore high rate of production of male progeny was obtained. We observed higher rates of fertilization success in the Wolbachia-infected lines that resulted in significantly higher female progeny production compared to the uninfected sib mates. Since diploid females are the result of successful fertilization due to haplodiploidy sex determination system in this insect, our results indicate that Wolbachia promoted fertile sib mating in H. hebetor. Interestingly, the rate of adult emergence in the progeny of Wolbachia-infected sib mates were almost similar to the non-sib mate crosses and significantly more than those observed in the uninfected sib mate crosses. We support the idea that Wolbachia modulate inbreeding avoidance and promote sib mating and also mitigate inbreeding depression. The wasp Habrobracon hebetor siblings infected with Wolbachia show higher rates of fertilization success and higher adult emergence rates compared to the uninfected sib mates. By promoting successful sex with siblings and increasing the probability of female progeny, Wolbachia enhance their transmission to the next generation and also mitigate inbreeding depression. This is an undescribed effect of Wolbachia (symbiont) on the host reproduction.

evolutionary biology↗

bioRxiv2019

Wolbachia successfully replicate in a newly established horn fly, Haematobia irritans irritans (L.) (Diptera: Muscidae) cell line

BACKGROUNDHaematobia spp., horn flies (HF) and buffalo flies (BF), are economically important ectoparasites of dairy and beef cattle. Control of these flies relies mainly on the treatment of cattle with chemical insecticides. However, the development of resistance to commonly used compounds is compromising the effectiveness of these treatments and alternative methods of control are required. Wolbachia are maternally transmitted endosymbiotic bacteria of arthropods that cause various reproductive distortions and fitness effects, making them a potential candidate for use in the biological control of pests. RESULTSHere we report the successful establishment of a continuous HF cell line (HIE-18) from embryonic cells and its stable transinfection with Wolbachia strain wAlbB native to mosquitoes, and wMel and wMelPop native to Drosophila melanogaster. The established HIE-18 cells are typically round and diploid with ten chromosomes (2n = 10) or tetraploid with 20 chromosomes (4n=20) having a doubling time of 67.2 hours. Wolbachia density decreased significantly in the HIE-18 cells in the first 48 hours of infection, possibly due to overexpression of antimicrobial peptides through the Imd immune signalling pathway. However, density recovered after this time and stably Wolbachia-infected HIE-18 cell lines have now all been subcultured more than 50 times as persistently infected lines. CONCLUSIONThe amenability of HF to infection with different strains of Wolbachia suggests the potential for use of Wolbachia in novel approaches for the control of Haematobia spp. Further, the availability of the HIE-18 cell line will provide an important resource for the study of genetics, host-parasite interactions and chemical resistance in Haematobia populations.

microbiology↗

bioRxiv2019

Complete genome assembly of the Wolbachia endosymbiont of the horn fly Haematobia irritans irritans: a supergroup A strain with multiple horizontally acquired cytoplasmic incompatibility genes

The horn fly, Haematobia irritans irritans, is a hematophagous parasite of livestock distributed throughout Europe, Africa, Asia, and the Americas. Welfare losses on livestock due to horn fly infestation are estimated to cost between USD 1-2.5 billion annually in North America and Brazil. The endosymbiotic bacterium Wolbachia pipientis is a maternally inherited manipulator of reproductive biology in arthropods and naturally infects laboratory colonies of horn flies from Kerrville, USA and Alberta, Canada, but has also been identified in wild-caught samples from Canada, USA, Mexico and Hungary. Reassembly of PacBio long-read and Illumina genomic DNA libraries from the Kerrville H. i. irritans genome project allowed for a complete and circularised 1.3 Mb Wolbachia genome (wHae). Annotation of wHae yielded 1249 coding genes, 34 tRNAs, three rRNAs, and five prophage regions. Comparative genomics and whole genome Bayesian evolutionary analysis of wHae compared to published Wolbachia genomes suggests that wHae is most closely related to and diverged from Wolbachia supergroup A strains known to infect Drosophila spp. Whole-genome synteny analyses between wHae and closely related genomes indicates that wHae has undergone convoluted genome rearrangements while maintaining high nucleotide identity. Comparative analysis of the cytoplasmic incompatibility (CI) genes of wHae suggests two phylogenetically distinct CI loci and acquisition of another CifB homolog from phylogenetically distant supergroup A Wolbachia strains suggesting horizontal acquisition of these loci. The wHae genome provides a resource for future examination of the impact Wolbachia may have in both biocontrol and potential insecticide resistance of horn flies.\n\nImportanceHorn flies, Haematobia irritans, are obligate hematophagous parasites of cattle having significant effects on production and animal welfare. Control of horn flies mainly relies on the use of insecticides, but issues with resistance have increased interest in development of alternative means of control. Wolbachia pipientis is an endosymbiont bacterium known to have a range of effects on host reproduction such as induction of cytoplasmic incompatibility, feminization, male killing, and also impacts on vector transmission. These characteristics of Wolbachia have been exploited in biological control approaches for a range of insect pests. Here we report the assembly and annotation of the circular genome of the Wolbachia strain of the Kerrickville, USA horn fly (wHae). Annotation of wHae suggests its unique features including the horizontal acquisition of additional transcriptionally active cytoplasmic incompatibility loci. This study will provide the foundation for future Wolbachia-induced biological effect studies for control of horn flies.

microbiology↗

bioRxiv2019

A positively selected, common, missense variant in FBN1 confers a 2.2 centimeter reduction of height in the Peruvian population

Peruvians are among the shortest people in the world. To understand the genetic basis of short stature in Peru, we examined an ethnically diverse group of Peruvians and identified a novel, population-specific, missense variant in FBN1 (E1297G) that is significantly associated with lower height in the Peruvian population. Each copy of the minor allele (frequency = 4.7%) reduces height by 2.2 cm (4.4 cm in homozygous individuals). This is the largest effect size known for a common height-associated variant. This variant shows strong evidence of positive selection within the Peruvian population and is significantly more frequent in Native American populations from coastal regions of Peru compared to populations from the Andes or the Amazon, suggesting that short stature in Peruvians is the result of adaptation to the coastal environment. One Sentence SummaryA mutation found in Peruvians has the largest known effect on height for a common variant. This variant is specific to Native American ancestry.

genomics↗

bioRxiv2018

Wolbachia induce cytoplasmic incompatibility and affect mate preference in Habrobracon hebetor to increase the chance of its transmission to the next generation

Wolbachia are common intracellular bacteria that are generally found in arthropods including a high proportion of insects and also some nematodes. This intracellular symbiont can affect sex ratio with a variety of reproductive anomalies in the host, including cytoplasmic incompatibility (CI) in haplodiploides. In this study, we questioned if the parasitoid wasp, Habrobracon hebetor (Hym.: Braconidae), which is one of the most important biological control agents of many lepidopteran larvae, is infected with Wolbachia. To test this, DNA was extracted from adult insects and subjected to PCR using specific primers to Wolbachia target genes. The results showed high rate of Wolbachia infection in this parasitoid wasp. To find out the biological function of Wolbachia in H. hebetor, we removed this bacterium from the wasps using antibiotic treatment (cured wasps). Results of the crossing experiments revealed that Wolbachiainduced CI in H. hebetor in which cured females crossed with infected males produced only males, while in the progeny of other crosses, both males and females were observed. Also, our result showed that the presence of Wolbachia in the females increased fecundity and female offspring of this parasitoid wasp. However, the presence of Wolbachia in the males had no significant effect on the fecundity and female production, but might have incurred costs. We also investigated the effect of Wolbachia on mate choice and found that Wolbachia affects mating behavior of H. hebetor. Together, we show that Wolbachia induce CI in H. hebetor and affect host mating behavior in favor of its transmission. Wolbachia utilize these strategies to increase the frequency of infected females in the host population.

zoology↗

bioRxiv2018

Density dependent enhancement effect of Wolbachia and the host RNAi response to a densovirus in Aedes cells

The endosymbiotic bacterium Wolbachia pipientis has been shown to restrict a range of RNA viruses in Drosophila melanogaster and transinfected dengue mosquito, Aedes aegypti. Here, we show that Wolbachia infection enhances replication of Aedes albopictus densovirus (AalDNV-1), a single stranded DNA virus, in Aedes cell lines in a density-dependent manner. Analysis of previously produced small RNAs of Aag2 cells showed that Wolbachia-infected cells produced greater proportions of viral derived short interfering RNAs as compared to uninfected cells. Additionally, we found production of viral derived PIWI-like RNAs (vpiRNA) produced in response to AalDNV-1 infection. Nuclear fractions of Aag2 cells produced a primary vpiRNA signature U1 bias whereas the typical \"ping-pong\" signature (U1 - A10) was evident in the cytoplasmic fraction. This is the first report of the density-dependent enhancement of DNA viruses by Wolbachia. Further, we report the generation of vpiRNAs in a DNA virus-host interaction for the first time.

microbiology↗

bioRxiv2018

Progression of recent Mycobacterium tuberculosis exposure to active tuberculosis is a highly heritable complex trait driven by 3q23 in Peruvians

Among 1.8 billion people worldwide infected with Mycobacterium tuberculosis, 5-15% are expected to develop active tuberculosis (TB). Approximately half of these will progress to active TB within the first 18 months after infection, presumably because they fail to mount the initial immune response that contains the local bacterial spread. The other half will reactivate their latent infection later in life, likely triggered by a loss of immune competence due to factors such as HIV-associated immunosuppression or ageing. This natural history suggests that undiscovered host genetic factors may control early progression to active TB. Here, we report results from a large genome-wide genetic study of early TB progression. We genotyped a total of 4,002 active TB cases and their household contacts in Peru and quantified genetic heritability [Formula] of early TB progression to be 21.2% under the liability scale. Compared to the reported [Formula] of genome-wide TB susceptibility (15.5%), this result indicates early TB progression has a stronger genetic basis than population-wide TB susceptibility. We identified a novel association between early TB progression and variants located in an enhancer region on chromosome 3q23 (rs73226617, OR=1.19; P < 5x10-8). We used in silico and in vitro analyses to identify likely functional variants and target genes, highlighting new candidate mechanisms of host response in early TB progression.

genetics↗

bioRxiv2018

Algorithm for Reliable Detection of Beat Onsets in Cerebral Blood Flow Velocity Signals

Transcranial Doppler (TCD) ultrasound has been demonstrated to be a valuable tool for assessing cerebral hemodynamics via measurement of cerebral blood flow velocity (CBFV), with a number of established clinical indications. However, CBFV waveform analysis depends on reliable pulse onset detection, an inherently difficult task for CBFV signals acquired via TCD. We study the application of a new algorithm for CBFV pulse segmentation, which locates pulse onsets in a sequential manner using a moving difference filter and adaptive thresholding. The test data set used in this study consists of 92,012 annotated CBFV pulses, whose quality is representative of real world data. On this test set, the algorithm achieves a true positive rate of 99.998% (2 false negatives), positive predictive value of 99.998% (2 false positives), and mean temporal offset error of 6.10 {+/-} 4.75 ms. We do note that in this context, the way in which true positives, false positives, and false negatives are defined caries some nuance, so care should be taken when drawing comparisons to other algorithms. Additionally, we find that 97.8% and 99.5% of onsets are detected within 10 ms and 30 ms, respectively, of the true onsets. The algorithms performance in spite of the large degree of variation in signal quality and waveform morphology present in the test data suggests that it may serve as a valuable tool for the accurate and reliable identification of CBFV pulse onsets in neurocritical care settings.

bioinformatics↗