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Results for “Automated phenotyping”

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PubMed2025

Automated Deep Learning-Based Detection of Early Atherosclerotic Plaques in Carotid Ultrasound Imaging.

BACKGROUND: Carotid plaque presence is associated with cardiovascular risk, even among asymptomatic individuals. While deep learning has shown promise for carotid plaque phenotyping in patients with advanced atherosclerosis, its application in population-based settings of asymptomatic individuals remains unexplored. METHODS: We developed a YOLOv8-based model for plaque detection using carotid ultrasound images from 19,499 participants of the population-based UK Biobank (UKB) and fine-tuned it for external validation in the BiDirect study (N = 2,105). Cox regression was used to estimate the impact of plaque presence and count on major cardiovascular events. To explore the genetic architecture of carotid atherosclerosis, we conducted a genome-wide association study (GWAS) meta-analysis of the UKB and CHARGE cohorts. Mendelian randomization (MR) assessed the effect of genetic predisposition to vascular risk factors on carotid atherosclerosis. RESULTS: Our model demonstrated high performance with accuracy, sensitivity, and specificity exceeding 85%, enabling identification of carotid plaques in 45% of the UKB population (aged 47-83 years). In the external BiDirect cohort, a fine-tuned model achieved 86% accuracy, 78% sensitivity, and 90% specificity. Plaque presence and count were associated with risk of major adverse cardiovascular events (MACE) over a follow-up of up to seven years, improving risk reclassification beyond the Pooled Cohort Equations. A GWAS meta-analysis of carotid plaques uncovered two novel genomic loci, with downstream analyses implicating targets of investigational drugs in advanced clinical development. Observational and MR analyses showed associations between smoking, LDL cholesterol, hypertension, and odds of carotid atherosclerosis. CONCLUSIONS: Our model offers a scalable solution for early carotid plaque detection, potentially enabling automated screening in asymptomatic individuals and improving plaque phenotyping in population-based cohorts. This approach could advance large-scale atherosclerosis research.

atherosclerosis↗

PubMed2006

Automating resequencing-based detection of insertion-deletion polymorphisms.

Structural and insertion-deletion (indel) variants have received considerable recent attention, partly because of their phenotypic consequences. Among these variants, the most common are small indels ( approximately 1-30 bp). Identifying and genotyping indels using sequence traces obtained from diploid samples requires extensive manual review, which makes large-scale studies inconvenient. We report a new algorithm, implemented in available software (PolyPhred version 6.0), to help automate detection and genotyping of indels from sequence traces. The algorithm identifies heterozygous individuals, which permits the discovery of low-frequency indels. It finds 80% of all indel polymorphisms with almost no false positives and finds 97% with a false discovery rate of 10%. Additionally, genotyping accuracy exceeds 99%, and it correctly infers indel length in 96% of the cases. Using this approach, we identify indels in the HapMap ENCODE regions, providing the first report of these polymorphisms in this data set.

Algorithms↗

PubMed2003

An autosomal dominant bull's-eye macular dystrophy (MCDR2) that maps to the short arm of chromosome 4.

PURPOSE: To describe the phenotype of an autosomal dominant macular dystrophy and identify the chromosomal locus. METHODS: Eleven members of a five-generation, nonconsanguineous British family were examined clinically and also underwent automated perimetry, electrodiagnostic testing, fundus fluorescein angiography, and fundus autofluorescence imaging. Blood samples were taken for DNA extraction and linkage analysis was performed. RESULTS: The phenotype is characterized by bull's-eye macular dystrophy first evident in the first or second decade of life. There is mild visual impairment, central scotomata, and electrophysiological testing indicates that most affected individuals have disease confined to the central retina but older subjects have more widespread rod and cone abnormalities, demonstrated by flash ERG. Genetic linkage analysis established linkage to chromosome 4 at p15.2-16.3 with a maximum lod score of 3.03 at a recombination fraction of 0.00 for marker D4S391. The locus for this autosomal dominant macular dystrophy lies between flanking markers D4S3023 and D4S3022, and overlaps the Stargardt 4 locus. CONCLUSIONS: A new locus was identified for a bull's-eye macular dystrophy on the short arm of chromosome 4.

Adolescent↗

PubMed2005

Reliability assessment of an automated forced swim test device using two mouse strains.

The Porsolt forced swim test (FST) is one of the most widely used behavioral tests in the evaluation of the antidepressant effects of drugs. It is based on the fact that these drugs reduce the depression-related behaviors of learned helplessness. The model has been modified for use in mice. In contrast to rats, mice are exposed to forced swimming only once and their immobility behavior is measured and considered a "depression-like" phenotype. Like many other behavioral tests, FST can be affected by observer-related artifacts. In recent years, automated testing systems have been developed to decrease artifacts that may greatly influence the interpretation of results. In this work, we used two strains of mice, i.e., C3H/HeJ and C57BL/6J, which differ in their FST immobility times. We employed a new commercially available automated FST device and a blinded observer-based FST, and we examined their ability to measure behavioral differences between these two mouse strains. Our results suggest that the tested automated FST system generates reliable data comparable to results obtained by trained observers.

Algorithms↗

PubMed2007

Tools for quantitative and validated measurements of cells.

In this chapter, we describe the preparation of thin films of collagen that can serve as reference materials for assuring reproducible and predictable cell responses. Subtle differences in the molecular-scale characteristics of extracellular matrix proteins, including the supramolecular structure of type 1 collagen, can have tremendous influences on cell state and cell-signaling pathways; therefore the careful control and analysis of the culture surface is critical to assure a relevant and consistent response in cell-based assays. We also describe how cell-phenotypic parameters such as morphology, proliferation, and green fluorescent protein expression can be unambiguously quantified in adherent cells by automated fluorescence microscopy or high content screening. Careful consideration of protocols, and the use of fluorescent reference materials, are essential to assure day-to-day and instrument-to-instrument interoperability. The ability to collect quantitative data on large numbers of cells in homogeneous matrix environments allows assessment of the range of phenotypes that are reproducibly expressed in clonal cell populations. The inherent distribution of responses in a cell population will determine how many cells must be measured to reach an accurate determination of cellular response.

Animals↗

PubMed2002

Characterization of sewage waters by biochemical fingerprinting of Enterococci.

Three sewage waters with different sources of faecal pollution (human, pig and mixed origin) were analysed. Enumeration of Enterococci was performed and representative strains for each sample were isolated. Biochemical fingerprints of these strains were obtained by using a simple automated microplate system. The structure and composition of the Enterococci populations were studied and the most representative biochemical profiles were determined by cluster analysis. The diversity index was high for all the sewage waters sampled. The enterococcal populations detected in the three kinds of sewage waters were similar. Although many of the representative strains were found in the three kinds of samples, some strains were detected only in human sewage and others only in pig slurry.

Animals↗

PubMed2001

History and development of antimicrobial susceptibility testing methodology.

Antimicrobial susceptibility testing (AST) is performed daily on bacterial isolates in clinical laboratories. The techniques employed are often taken for granted. This paper traces the history and development of some methods still in common use for routine AST, e.g. disc diffusion and agar dilution. It was quickly recognized by early investigators that there were many variables affecting the results of these tests. Consequently, there was recognition (as early as the late 1950s) that standardization of these techniques was required. This need has led to many organizations producing standardized AST methodologies. Although some disc diffusion techniques that generated results within 4-6 h were described, most relied on 18-24 h incubation before a result was available. The clinical and economic pressures for rapid methods with low labour input led to the development of semi-automated and automated AST methodologies in the 1970s. Until 10 years ago, AST techniques relied on phenotypically testing the bacteria isolated. However, to increase the speed and reliability of resistance testing, the use of a genotypic approach has been advocated. The limitations and benefits of this new approach are discussed.

History, 19th Century↗

PubMed2000

John von Neumann and the evolutionary growth of complexity: looking backward, looking forward...

In the late 1940s John von Neumann began to work on what he intended as a comprehensive "theory of [complex] automata." He started to develop a book length manuscript on the subject in 1952. However, he put it aside in 1953, apparently due to pressure of other work. Due to his tragically early death in 1957, he was never to return to it. The draft manuscript was eventually edited, and combined for publication with some related lecture transcripts, by Burks in 1966. It is clear from the time and effort that von Neumann invested in it that he considered this to be a very significant and substantial piece of work. However, subsequent commentators (beginning even with Burks) have found it surprisingly difficult to articulate this substance. Indeed, it has since been suggested that von Neumann's results in this area either are trivial, or, at the very least, could have been achieved by much simpler means. It is an enigma. In this paper I review the history of this debate (briefly) and then present my own attempt at resolving the issue by focusing on an analysis of von Neumann's problem situation. I claim that this reveals the true depth of von Neumann's achievement and influence on the subsequent development of this field, and further that it generates a whole family of new consequent problems, which can still serve to inform - if not actually define - the field of artificial life for many years to come.

Artificial Intelligence↗

PubMed2002

Rokitamycin: bacterial resistance to a 16-membered ring macrolide differs from that to 14- and 15-membered ring macrolides.

Rokitamycin is the latest semi-synthetic 16-membered ring macrolide introduced into clinical practice. It is characterized by greater hydrophobicity, better bacterial uptake and a slower release, more cohesive ribosomal binding, and a longer post-antibiotic-effect (PAE) than can be observed with other available 14-, 15- and 16-membered ring macrolides. Rokitamycin exerts its activity on strains that harbor inducible erm genes or the efflux gene, mef(A). It has also been reported to be more active in vitro than other 16-membered ring macrolides. However, these recognized features are not fully exploited yet because current automated test procedures used in many microbiological laboratories determine susceptibility only to erythromycin or clarithromycin. Resistance to 16-membered ring macrolides cannot be predicted solely on the basis of known resistance to erythromycin or clarithromycin as revealed by an automated susceptibility assay. At least equally important is the knowledge of the bacterial resistance phenotype. This is underlined by the existence of Gram-positive coccal strains resistant to erythromycin and other 14-,15-membered ring macrolides but susceptible to 16-membered ring macrolides. Since the local prevalence of erythromycin phenotypes is generally unknown but might determine the outcome of treatment, the procedure for identifying the phenotypes in erythromycin-resistant strains (which can be easily and cheaply performed using the two- or three-disk assay) should become routine, at least in the countries in which 16-membered ring macrolides are used. This approach should help to optimize the use of macrolides, improve our knowledge of the local prevalence of phenotypes resistant to erythromycin, and offer the possibility of treating infections caused by certain types of erythromycin-resistant pathogens.

Anti-Bacterial Agents↗

PubMed1993

[Automated genetic register and computer support for the physician's diagnostic decisions].

Computer-based genetical register "GENREG" allows to carry out a prophylactic medical examination for families with children, having hereditary diseases, multifactorial pathology and congenital developmental defects of various nature, and also epidemiological examination. Automated consultative system for pre-laboratory diagnosis of genetically determined diseases after the phenotypical manifestations "DIAGEN" allows to identify up to 1200 nosologic units; diagnostic value (or weight) of the signs according to physician's evaluation is taken into consideration. The system sorts out a narrow differential-and-diagnostic row and information about specific laboratory and functional changes for every selected diagnosis. Efficiency of the system is over 94% (after the next laboratory findings). The results of computer diagnosis and final physician's diagnosis, and also questionnaire of a child are stored in archives (files) of the "DIAGEN" system. Both of the systems are realized on PC/AT IBM-compatible computer.

Child↗

PubMed2004

Feminization of female leukophore-free strain of Japanese medaka (Oryzias latipes) exposed to 17beta-estradiol.

The recently developed female leukophore-free (FLFII) strain of Japanese medaka (Oryzias latipes) carries DNA markers for the identification of genotypic sex. Information regarding genotypic sex is useful for tests in which endocrine-disrupting compounds may masculinize or feminize fish. In the present study, methods were developed to automate DNA extraction and profiling for rapid determination of genotypic sex. Adequate amounts of DNA were isolated by robotic extraction procedures from the caudal fin. New primers were developed to include an 18-base pair segment that is in the X chromosome of female medaka but is absent in the Y chromosome of male medaka. Automated profiling methods with 96-well plates permitted analysis of the genomic sex of medaka at rates of up to 500 fish/d. We investigated the sensitivity of the FLFII strain to the feminizing effects of the potent estrogen 17beta-estradiol (E2), and we compared this sensitivity to that of a wild strain that has been used widely in the study of endocrine-disrupting compounds. All FLFII medaka exposed to 1 microg/L of E2 (n = 50) had the female gonadal phenotype (i.e., ovaries), and all but one wild-strain medaka exposed to 1 microg/L of E2 (i.e., 47 of 48 fish) had the female gonadal phenotype, indicating that the FLFII and wild strains have approximately equal sensitivities to the feminizing effects of E2. Analysis of the genotype of FLFII medaka confirmed that 100% of fish with the male genotype had been feminized to the female gonadal phenotype. The FLFII strain is an excellent teleost model for detecting feminization or masculinization of fish, and automated methods can be used for rapid analysis of the genotypic sex of FLFII medaka.

Animals↗

PubMed2006

Automated cell lineage tracing in Caenorhabditis elegans.

The invariant cell lineage and cell fate of Caenorhabditis elegans provide a unique opportunity to decode the molecular mechanisms of animal development. To exploit this opportunity, we have developed a system for automated cell lineage tracing during C. elegans embryogenesis, based on 3D, time-lapse imaging and automated image analysis. Using ubiquitously expressed histone-GFP fusion protein to label cells/nuclei and a confocal microscope, the imaging protocol captures embryogenesis at high spatial (31 planes at 1 microm apart) and temporal (every minute) resolution without apparent effects on development. A set of image analysis algorithms then automatically recognizes cells at each time point, tracks cell movements, divisions and deaths over time and assigns cell identities based on the canonical naming scheme. Starting from the four-cell stage (or earlier), our software, named starrynite, can trace the lineage up to the 350-cell stage in 25 min on a desktop computer. The few errors of automated lineaging can then be corrected in a few hours with a graphic interface that allows easy navigation of the images and the reported lineage tree. The system can be used to characterize lineage phenotypes of genes and/or extended to determine gene expression patterns in a living embryo at the single-cell level. We envision that this automation will make it practical to systematically decipher the developmental genes and pathways encoded in the genome of C. elegans.

Animals↗

PubMed2000

Molecular and phenotypic characterization of Pseudomonas spp. isolated from milk.

Putative Pseudomonas spp. isolated predominantly from raw and processed milk were characterized by automated ribotyping and by biochemical reactions. Isolates were biochemically profiled using the Biolog system and API 20 NE and by determining the production of proteases, lipases, and lecithinases for each isolate. Isolates grouped into five coherent clusters, predominated by the species P. putida (cluster A), P. fluorescens (cluster B), P. fragi (as identified by Biolog) or P. fluorescens (as identified by API 20 NE) (cluster C), P. fragi (as identified by Biolog) or P. putida (as identified by API 20 NE) (cluster D), and P. fluorescens (cluster E). Isolates within each cluster also displayed similar enzyme activities. Isolates in clusters A, C, and D were generally negative for all three enzyme activities; isolates in cluster B were predominantly positive for all three enzyme activities; and isolates in cluster E were negative for lecithinase but predominantly positive for protease and lipase activities. Thus, only isolates from clusters B and E produced enzyme activities associated with dairy product flavor defects. Thirty-eight ribogroups were differentiated among the 70 isolates. Ribotyping was highly discriminatory for dairy Pseudomonas isolates, with a Simpson's index of discrimination of 0.955. Isolates of the same ribotype were never classified into different clusters, and ribotypes within a given cluster generally showed similar ribotype patterns; thus, specific ribotype fragments may be useful markers for tracking the sources of pseudomonads in dairy production systems. Our results suggest that ribogroups are generally homogeneous with respect to nomenspecies and biovars, confirming the identification potential of ribotyping for Pseudomonas spp.

Animals↗

PubMed2006

Determining human immunodeficiency virus coreceptor use in a clinical setting: degree of correlation between two phenotypic assays and a bioinformatic model.

Two recombinant phenotypic assays for human immunodeficiency virus (HIV) coreceptor usage and an HIV envelope genotypic predictor were employed on a set of clinically derived HIV type 1 (HIV-1) samples in order to evaluate the concordance between measures. Previously genotyped HIV-1 samples derived from antiretroviral-naïve individuals were tested for coreceptor usage using two independent phenotyping methods. Phenotypes were determined by validated recombinant assays that incorporate either an approximately 2,500-bp ("Trofile" assay) or an approximately 900-bp (TRT assay) fragment of the HIV envelope gp120. Population-based HIV envelope V3 loop sequences ( approximately 105 bp) were derived by automated sequence analysis. Genotypic coreceptor predictions were performed using a support vector machine model trained on a separate genotype-Trofile phenotype data set. HIV coreceptor usage was obtained from both phenotypic assays for 74 samples, with an overall 85.1% concordance. There was no evidence of a difference in sensitivity between the two phenotypic assays. A bioinformatic algorithm based on a support vector machine using HIV V3 genotype data was able to achieve 86.5% and 79.7% concordance with the Trofile and TRT assays, respectively, approaching the degree of agreement between the two phenotype assays. In most cases, the phenotype assays and the bioinformatic approach gave similar results. However, in cases where there were differences in the tropism results, it was not clear which of the assays was "correct." X4 (CXCR4-using) minority species in clinically derived samples likely complicate the interpretation of both phenotypic and genotypic assessments of HIV tropism.

Computational Biology↗

PubMed1993

Variations in biochemical phenotypes and phage types of Salmonella enteritidis in Germany 1980-92.

The Phene Plate system for typing Salmonella serotypes (PhP-S) is a simple automated typing method based on biochemical fingerprinting. It gives a quantitative value of the metabolism of various substrates by measuring the speed and intensity of each reaction. The 'biochemical fingerprint' of each isolate is used to calculate similarities among the tested strains with a personal computer program. We used this system to examine a collection of 86 strains of Salmonella enteritidis isolated from human sporadic cases in Germany between 1980 and 1992. Twenty-three biochemical phenotypes (BPTs) consisting of 9 common (C) and 14 single (S) BPTs were identified. BPTs C2 and C4 containing 20 and 36 strains respectively accounted for 65% of the isolates. Strains of BPT C2 were found over a wide period of time whereas strains of BPT C4 were isolated during the period between 1988 and 1992. With phage typing, 11 discrete phage types (PTs) and 18 strains designated as non-specific type (NST) were identified. PTs 4 and 8 with 39 and 17 strains respectively were the dominant PTs. Strains of PT 8 were isolated over a wide period of time whereas all (except one) strains of PT 4 were isolated between 1988 and 1992. Combination of biochemical fingerprinting and phage typing divided the strains into 25 phenotypes (BPT:PTs). Whilst phenotype C2:8 was found over a number of different years, phenotype C4:4 was isolated only between 1988 and 1992. These findings indicate the presence of one persistent and one recently emerged phenotype among S. enteritidis strains in Germany.(ABSTRACT TRUNCATED AT 250 WORDS)

Bacterial Typing Techniques↗

PubMedDate not supplied

Phenotypic markers for selection of nematode-resistant sheep.

Nematode-resistance of an animal can be defined as an enhanced natural ability, relative to its peers, to both prevent establishment of larval nematodes and evict any that do establish. These parameters are not measurable in a practical sense and consequently nematode-resistance has usually been defined in terms of low faecal nematode egg counts (FEC). Studies in New Zealand and Australia have demonstrated that nematode-resistance, as measured by FEC, has a heritability of about 0.3 in Romney and Merino sheep. However as a selection trait FEC has practical limitations and its use may incur production penalties through withholding drench treatment for prolonged periods or from a need for artificial challenge. FEC is influenced by the level and composition of a natural nematode challenge and especially the expression of the immune response. Thus immunological parameters which reflect the underlying genetic resistance could potentially be used as phenotypic markers. Ideally, a useful phenotypic marker would be easy to sample and its assay would be inexpensive and able to be automated, in addition to being strongly correlated with nematode-resistance. Results from several New Zealand trials have indicated that antibody levels (particularly IgG1) to excretory/secretory antigens of L3 nematodes such as Trichostrongylus colubriformis may meet these criteria. Levels of antibody against L3 antigens are also independent of on-farm drenching strategies. Blood eosinophil count has also been considered for use as a selection parameter but a high degree of sample variability reduces its potential. Other immunological parameters associated with nematode-resistance which have potential as phenotypic markers include serum nematode-specific IgE and products of mucosal mast cells such as proteinases. It is likely that as the critical immune responses of sheep to nematodes become more clearly defined, new immunological parameters with potential for use as phenotypic markers will be found. The definition of these immune responses will also assist in the identification and characterization of genetic markers.

Animals↗

PubMed2005

Detection of weak D with a fully automated solid-phase red cell adherence system.

BACKGROUND: Microplate agglutination methods (MAMs) and column agglutination technology are widely employed for red cell typing and can be automated. Some tests, however, such as detection of weak D, require manual testing. The possibility of detecting weak D by a solid-phase RBC adherence (SPRCA) test was studied in a fully automated system. STUDY DESIGN AND METHODS: The results of 2609 blood samples, characterized as being D- or with a incomplete agglutination reaction, were analyzed for the presence of the weak D phenotype. The 2609 samples were tested by a weak D tube test (antiglobulin method) and a weak D-test with the new SPRCA method. When weak D was detected, which D epitope was involved and whether it was associated with a partial D phenotype were determined. RESULTS: Weak D was detected in 60 (2.3%) of the 2609 samples. The 60 samples that were weak D by the tube test were also weak D+ with the new automated SPRCA test. The sensitivity and specificity for the new weak D typing method were 100 percent, when compared with the standard weak D manual test. CONCLUSIONS: These results support the possibility of performing weak D detection with a SPRCA fully automated system. These preliminary results are encouraging, showing good sensitivity and specificity of the test. Detection of weak D will permit full automation of blood typing.

Blood Banking↗

PubMedDate not supplied

Acetylator phenotyping via analysis of four caffeine metabolites in human urine by micellar electrokinetic capillary chromatography with multiwavelength detection.

The simultaneous analysis of 5-acetylamino-6-formylamino-3-methyluracil (AFMU), 5-acetylamino-6-amino-3-methyluracil (AAMU), 1-methylxanthine (1X) and 1-methyluric acid (1U), the four urinary metabolites of caffeine employed for acetylator phenotyping in man, by micellar electrokinetic capillary chromatography (MECC) is reported. Using on-column fast scanning multiwavelength detection is shown to permit unambiguous identification of AAMU, AFMU, 1X and 1U in the three-dimensional electropherograms obtained with both direct urine injection or application of extracted urine. The phenotype status of a number of healthy volunteers, some with known acetylator status, were determined using peak height ratios of AFMU/1X, (AFMU + AAMU)/1X and compared to those obtained by high performance liquid chromatography (HPLC) employing the AFMU/1X peak height ratio. Another set of MECC data was obtained after deliberate conversion of AFMU to AAMU, the results being expressed by AAMU/1X,AAMU/(1U + 1X) or AAMU/(AAMU + 1U + 1X) ratios. The data suggest that most reliable data are obtained when phenotyping is conducted under conditions of complete conversion of AFMU to AAMU. Phenotyping employing caffeine and analysis of its urinary metabolites by MECC is shown to be simple and, with automated instruments, potentially suitable for routine use and large-scale population analysis. The agreement of MECC data obtained from three different instruments demonstrates the high level of maturity of this emerging technology.

Acetylation↗