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 Read source abstracts and check manuscript versions; preprints are not peer reviewed.

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At least 325 records · Page 18Linked to original sources

bioRxiv2017

TMEM230 is not a gene for Parkinson disease

Deng et al. report the discovery of TMEM230 c.422G>T (p.Arg141Leu) mutation as a cause of late-onset, autosomal dominant Parkinsons disease (PD)1 in the same pedigree in which we previously assigned DNAJC13 c.2564A>G (p.Asn855Ser) as pathogenic2. The chromosome 20pter-p12 locus was discovered by short tandem-repeat (STR) genotyping and linkage analysis, with subsequent exome sequencing in four affected (II-4, III-1, III-20 and III-26) and one unaffected family member. Deng et al. state the rationale for their re-analysis was the inconsistency of genotype-phenotype correlations for DNAJC13 c.2564A>G (p.Asn855Ser), this mutation being absent in three affected family members (II-1, III-1 and III-23). However, two of these suffer atypical parkinsonism; II-l had clinical and pathologically-proven progressive supranuclear palsy, not Lewy body PD, whereas his son developed symptoms mor ...

genetics↗

bioRxiv2017

Two sides of the same coin: monetary incentives concurrently improve and bias confidence judgments.

Decisions are accompanied by a feeling of confidence, i.e., a belief about the decision being correct. Confidence accuracy is critical, notably in high-stakes situations such as medical or financial decisionmaking. Here, we investigated how incentive motivation influences confidence accuracy by combining a perceptual task with a confidence incentivization mechanism. Importantly, by varying the magnitude and valence (gains or losses) of monetary incentives, we orthogonalized their motivational and affective components. Corroborating theories of rational decision-making and motivation, our results first reveal that the motivational value of incentives improves aspects of confidence accuracy. However, in line with a value-confidence interaction hypothesis we further show that the affective value of incentives concurrently biases confidence reports, thus degrading confidence accuracy. Finally, we demonstrate that the motivational and affective effects of incentives differentially impact how confidence builds on perceptual evidence. Altogether, these findings may provide new hints about confidence miscalibration in healthy or pathological contexts.

animal behavior and cognition↗

bioRxiv2017

Senescence associated protein degradation

Senescent cells accumulate with age and contribute to pathologies associated to old age. The senescent program can be induced by pro-cancer stimuli or is developmentally controlled. In cells forced to senesce by expression of oncogenes or short telomeres, aberrant activation of the ERK/MAP kinase signaling pathway leads to selective protein degradation by the ubiquitin proteasome system. The proteins affected by this process control key cellular processes known to be defective in senescent cells. We discuss the evidence supporting a general role for senescence associated protein degradation for organismal aging.

cell biology↗

bioRxiv2017

RNA Gelation in Repeat Expansion Disorders

Expansions of short nucleotide repeats in the protein coding and non-coding regions of >30 genes produce a variety of neurological and neuromuscular disorders including Huntingtons disease (CAG repeats), muscular dystrophy (CTG repeats) and amyotrophic lateral sclerosis (GGGGCC repeats) [1-3]. Expression of expanded repeats alone is sufficient to recapitulate disease pathology in animal models [4-6]. Repeat-containing transcripts accumulate in the nucleus as aberrant \"RNA foci\" [7-10] and sequester numerous RNA binding proteins [11,12], leading to a disruption of cellular homeostasis [13,14]. Interestingly, RNA foci, as well as the disease symptoms, only manifest at a critical threshold of nucleotide repeats: >30 for CAG/CTG expansions [1] and >7 for the GGGGCC expansion [15]. However, the reason for this characteristic threshold, as well as the molecular mechanism of foci formation, remain unresolved [16]. Here, we show that nucleotide repeat expansions in RNA create templates for multivalent Watson-Crick (CAG/CUG expansions) or Hoogsteen (GGGGCC expansion) base-pairing. These multivalent interactions cause purified RNAs containing repeat expansions to undergo a sol-gel transition and form micron-sized clusters. Reflecting an increase in the valency for intermolecular hybridization, the gelation of purified RNA only occurs above a critical number of trinucleotide or hexanucleotide repeats. These thresholds for in vitro RNA gelation are similar to those associated with manifestation of disease. By visualizing RNA in live cells, we show that nuclear foci form as a result of phase separation of the repeat-containing RNA and that these foci can be dissolved by agents that disrupt RNA gelation in vitro. Analogous to protein aggregation disorders, our results suggest that the sequence-specific gelation of RNAs could be a contributing factor to neurological disease.

biophysics↗

bioRxiv2017

Experience-induced forgetting by WT1 enables learning of sequential tasks.

Under physiological conditions, strength and persistence of memory must be regulated in order to produce behavioral flexibility. In fact, impairments in memory flexibility are associated with pathologies such as post-traumatic stress disorder or autism; however the underlying mechanisms that enable memory flexibility are still poorly understood. Here we identified the transcriptional repressor Wilms Tumor 1 (WT1) as a critical synaptic plasticity regulator that decreases memory strength, promoting memory flexibility. WT1 was activated in the hippocampus following induction of long-term potentiation (LTP) or learning. WT1 knockdown enhanced CA1 neuronal excitability, LTP and long-term memory whereas its over-expression weakened memory retention. Moreover, forebrain WT1-deficient mice showed deficits in both reversal, sequential learning tasks and contextual fear extinction, exhibiting impaired memory flexibility. We conclude that WT1 limits memory strength or promotes memory weakening, thus enabling memory flexibility, a process that is critical for learning from new experience.

neuroscience↗

bioRxiv2017

Asian lineage of Zika virus RNA pseudoknot may induce ribosomal frameshift and produce a new neuroinvasive protein ZIKV-NS1’

Zika virus (ZIKV) is a threat to humanity, and understanding its neuroinvasiveness is a major challenge. Microcephaly observed in neonates in Brazil is associated with ZIKV that belongs to the Asian lineage. What distinguishes the neuroinvasiveness between the RNA lineages from Asia and Africa is still unknown. Here we identify an aspect that may explain the different behavior between the two lineages. The distinction between the two groups is the occurrence of an alternative protein NS1 (ZIKV-NS1), which happens through a pseudoknot in the virus RNA that induces a ribosomal frameshift. Presence of NS1 protein is also observed in other Flavivirus that are neuroinvasive, and when NS1 production issuppressed, neuroinvasiveness is reduced.1 This evidence gives grounds to suggest that the ZIKV-NS1 occurring in the Asian lineage is responsible for neuro-tropism, which causes the neuro-pathologies associated with ZIKV infection, of which microcephaly is the most dev astating. The existence of ZIKV-NS1, which only exists in the Asian lineage, was inferred through bioinformatic methods, and it has yet to be experimentally observed. If its occurrence is confirmed, it will be a potential target in fighting the neuro-diseases associated with ZIKV.

epidemiology↗

bioRxiv2017

Genome-wide analysis of differential translation and differential translational buffering using anota2seq

mRNA translation plays an evolutionarily conserved role in homeostasis and when dysregulated results in various disorders. Optimal and universally applicable analytical methods to study transcriptome-wide changes in translational efficiency are therefore critical for understanding the complex role of translation regulation under physiological and pathological conditions. Techniques used to interrogate translatomes, including polysome- and ribosome-profiling, require adjustment for changes in total mRNA levels to capture bona fide alterations in translational efficiency. Herein, we present the anota2seq algorithm for such analysis using data from ribosome- or polysome-profiling quantified by DNA-microarrays or RNA sequencing, which outperforms current methods for identification of changes in translational efficiency. In contrast to available analytical methods, anota2seq also allows capture of an underappreciated mode for regulation of gene expression whereby translation acts as a buffering mechanism which maintains constant protein levels despite fluctuations in mRNA levels (\"translational buffering\"). Application of anota2seq shows that insulin affects gene expression at multiple levels, in a largely mTOR-dependent manner. Moreover, insulin induces levels of a subset of mRNAs independently of mTOR that undergo translational buffering upon mTOR inhibition. Thus, the universal anota2seq algorithm allows efficient and hitherto unprecedented interrogation of translatomes and enables studies of translational buffering which represents an unexplored mechanism for regulating of gene expression.

bioinformatics↗

bioRxiv2017

Functional Connectivity Dynamics of the Resting State across the Human Adult Lifespan

Functional Connectivity (FC) during resting-state or task conditions is not fixed but inherently dynamic. Yet, there is no consensus on whether fluctuations in FC may resemble isolated transitions between discrete FC states rather than continuous changes. This quarrel hampers advancing the study of dynamic FC. This is unfortunate as the structure of fluctuations in FC can certainly provide more information about developmental changes, aging, and progression of pathologies. We merge the two perspectives and consider dynamic FC as an ongoing network reconfiguration, including a stochastic exploration of the space of possible steady FC states. The statistical properties of this random walk deviate both from a purely "order-driven" dynamics, in which the mean FC is preserved, and from a purely "randomness-driven" scenario, in which fluctuations of FC remain uncorrelated over time. Instead, dynamic FC has a complex structure endowed with long-range sequential correlations that give rise to transient slowing and acceleration epochs in the continuous flow of reconfiguration. Our analysis for fMRI data in healthy elderly revealed that dynamic FC tends to slow down and becomes less complex as well as more random with increasing age. These effects appear to be strongly associated with age-related changes in behavioural and cognitive performance. HighlightsO_LIDynamic Functional Connectivity (dFC) at rest and during cognitive task performs a "complex" (anomalous) random walk. C_LIO_LISpeed of dFC slows down with aging. C_LIO_LIResting dFC replaces complexity by randomness with aging. C_LIO_LITask performance correlates with the speed and complexity of dFC. C_LI

neuroscience↗

bioRxiv2017

Treatment of Graft-versus-Host Disease by Echinomycin in a New Humanized Mouse Model

Drug development effort against GVHD is hampered by the lack of clinically relevant humanized animal models for preclinical testing. Current humanized GVHD models rely on adoptive transfer of a high number of human peripheral blood mononuclear cells (PBMCs) into immunodeficient mice. Here we report a novel humanized GVHD model by transplanting a small number of human BM cells into newborn NOD. SCID IL2ry0 (NSG) mice. Transplantation of human BM cells (BMT) causes acute GVHD, with lethality between 15 to 60 days. Pervasive human T-cell infiltration into multiple organs, including lung, intestine, skin, kidney, liver, and stomach, was observed in all mice analyzed. Surprisingly, the human T cells express high levels of hypoxia inducible factor 1 (HIF1) protein even under normoxic environment. Administration of Echinomycin, a potent inhibitor for HIF1, rapidly ablated HIF1 protein in T cells and gradually reduced the frequency of human cells in the peripheral blood and target organs. Echinomycin provides a sustained therapeutic effect, as demonstrated by dramatic reduction of clinical symptoms, pathology score and by doubling of the median life span of the chimeric mice. Our results reveal a critical role of HIF1 in GVHD and demonstrate that HIF1 inhibitors such as Echinomycin should be explored for clinical drug development against GVHD.

immunology↗

bioRxiv2017

Zebrafish models for human ALA-dehydratase-deficient porphyria (ADP) and hereditary coproporphyria (HCP) generated with TALEN and CRISPR-Cas9

Defects in the enzymes involved in heme biosynthesis result in a group of human metabolic genetic disorders known as porphyrias. Using a zebrafish model for human hepatoerythropoietic porphyria (HEP), caused by defective uroporphyrinogen decarboxylase (Urod), the fifth enzyme in the heme biosynthesis pathway, we recently have found a novel aspect of porphyria pathogenesis. However, no hereditable zebrafish models with genetic mutations of alad and cpox, encoding the second enzyme delta-aminolevulinate dehydratase (Alad) and the sixth enzyme coproporphyrinogen oxidase (Cpox), have been established to date. Here we employed site-specific genome-editing tools transcription activator-like effector nuclease (TALEN) and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) to generate zebrafish mutants for alad and cpox. These zebrafish mutants display phenotypes of heme deficiency, hypochromia, abnormal erythrocytic maturation and accumulation of heme precursor intermediates, reminiscent of human ALA-dehydratase-deficient porphyria (ADP) and hereditary coproporphyrian (HCP), respectively. Further, we observed altered expression of genes involved in heme biosynthesis and degradation and particularly down-regulation of exocrine pancreatic zymogens in ADP (alad-/-) and HCP (cpox-/-) fishes. These two zebrafish porphyria models can survive at least 7 days and thus provide invaluable resources for elucidating novel pathological aspects of porphyrias, evaluating mutated forms of human ALAD and CPOX, discovering new therapeutic targets and developing effective drugs for these complex genetic diseases. Our studies also highlight generation of zebrafish models for human diseases with two versatile genome-editing tools.

genetics↗

bioRxiv2017

Stroke-associated pattern of gene expression previously identified by machine-learning is diagnostically robust in an independent patient population.

PurposeOur group recently identified a ten gene pattern of differential expression in peripheral blood which may have utility for detection of stroke. The objective of this study was to assess the diagnostic capacity and temporal stability of this stroke-associated transcriptional signature in an independent patient population.\n\nMethodsPublically available whole blood microarray data generated from 23 ischemic stroke patients at 3, 5, and 24 hours post-symptom onset, along with 23 cardiovascular disease controls were obtained via the National Center for Biotechnology Information Gene Expression Omnibus. Expression levels of the ten candidate genes were extracted, compared between groups, and evaluated for their discriminatory ability at each time point.\n\nResultsWe observed a largely identical pattern of differential expression between stroke patients and controls across the ten candidate genes as reported in our prior work. Furthermore, the coordinate expression levels of the ten candidate genes were able to discriminate between stroke patients and controls with levels of sensitivity and specificity upwards of 90% across all three time points.\n\nConclusionsThese findings confirm the diagnostic robustness of the previously identified pattern of differential expression in independent patient population, and further suggest that it is temporally stable over the first 24 hours of stroke pathology.

genomics↗

bioRxiv2017

Rapid Sequential In Situ Multiplexing With DNA-Exchange-Imaging

To decipher the molecular mechanism of biological function, it is critical to map the molecular composition of individual cells in the context of their biological environment in situ. Immunofluorescence (IF) provides specific labeling for molecular profiling. However, conventional IF methods have finite multiplexing capabilities due to spectral overlap of the fluorophores. Various sequential imaging methods have been developed to circumvent this spectral limit, but are not widely adopted due to the common limitation of requiring multi-rounds of slow (typically over 2 hours at room temperature to overnight at 4 {degrees}C in practice) immunostaining. DNA-Exchange-Imaging is a practical platform for rapid in situ spectrally-unlimited multiplexing. This technique overcomes speed restrictions by allowing for single-step immunostaining with DNA-barcoded antibodies, followed by rapid (less than 10 minutes) buffer exchange of fluorophore-bearing DNA imager strands. By eliminating the need for multiple rounds of immunostaining, DEI enables rapid spectrally unlimited sequential imaging. The programmability of DNA-Exchange-Imaging allows us to further adapt it to diverse microscopy platforms (with Exchange-Confocal, Exchange-SIM, Exchange-STED, and Exchange-PAINT demonstrated here), achieving highly multiplexed in situ protein visualization in diverse samples (including neuronal and tumor cells as well as fresh-frozen or paraffin-embedded tissue sections) and at multiple desired resolution scales (from ~300 nm down to sub-20-nm). Validation highlights include 8-target imaging using single-channel Exchange-Confocal in tens of micron thick retina tissue sections in 2-3 hours (as compared to days required in principle by previous methods using comparable equipment), and 8-target super-resolution imaging with ~20 nm resolution using Exchange-PAINT in primary neurons. These results collectively suggest DNA-Exchange as a versatile, practical platform for rapid, highly multiplexed in situ imaging, potentially enabling new applications ranging from basic science, to drug discovery, and to clinical pathology.

bioengineering↗

bioRxiv2017

Development of a Novel CD4+ TCR Transgenic Line that Reveals a Dominant Role for CD8+ DC and CD40-Signaling in the Generation of Helper and CTL Responses to Blood Stage Malaria

We describe an MHC II (IAb)-restricted T cell receptor (TCR) transgenic mouse line that produces CD4+ T cells specific for Plasmodium species. This line, termed PbT-II, was derived from a CD4+ T cell hybridoma generated to blood-stage Plasmodium berghei ANKA (PbA). PbT-II cells responded to all Plasmodium species and stages tested so far, including rodent (PbA, P. berghei NK65, P. chabaudi AS and P. yoelii 17XNL) and human (P. falciparum) blood-stage parasites as well as irradiated PbA sporozoites. PbT-II cells can provide help for generation of antibody to P. chabaudi infection and can control this otherwise lethal infection in CD40L-deficient mice. PbT-II cells can also provide help for development of CD8+ T cell-mediated experimental cerebral malaria (ECM) during PbA infection. Using PbT-II CD4+ T cells and the previously described PbT-I CD8+ T cells, we determined the dendritic cell (DC) subsets responsible for immunity to PbA blood-stage infection. CD8+ DC (a subset of XCR1+ DC) were the major antigen presenting cell (APC) responsible for activation of both T cell subsets, though other DC also contributed to CD4+ T cell responses. Depletion of CD8+ DC at the beginning of infection prevented ECM development and impaired both Th1 and Tfh responses; in contrast, late depletion did not affect ECM. This study describes a novel and versatile tool for examining CD4+ T cell immunity during malaria and provides evidence that CD4+ T cell help, acting via CD40L signalling, can promote immunity or pathology to blood stage malaria largely through antigen presentation by CD8+ DC.

immunology↗

bioRxiv2017

Transcriptomic profiling of high-density Giardia foci encysting in the murine proximal intestine

Giardia is a highly prevalent, understudied protistan parasite causing significant diarrheal disease worldwide. Its life cycle consists of two stages: infectious cysts ingested from contaminated food or water sources, and motile trophozoites that colonize and attach to the gut epithelium, later encysting to form new cysts that are excreted into the environment. Current understanding of parasite physiology in the host is largely inferred from transcriptomic studies using Giardia grown axenically or in co-culture with mammalian cell lines. The dearth of information about the diversity of host-parasite interactions occurring within distinct regions of the gastrointestinal tract has been exacerbated by a lack of methods to directly and non-invasively interrogate disease progression and parasite physiology in live animal hosts. By visualizing Giardia infections in the mouse gastrointestinal tract using bioluminescent imaging (BLI) of tagged parasites, we recently showed that parasites colonize the gut in high-density foci that may cause localized pathology to the epithelium. Encystation is also initiated in these foci throughout the entire course of infection, yet how the physiology of parasites within high-density foci in the host gut differs from that of cells in laboratory culture is unclear. Here we use BLI to precisely select parasite samples from high-density foci in the proximal intestine to interrogate in vivo Giardia gene expression in the host. Relative to axenic culture, we noted significantly higher expression (> 10-fold) of oxidative stress, membrane transporter, and metabolic and structural genes associated with encystation in the high-density foci. These differences in gene expression within parasite foci in the host may reflect physiological changes associated with high-density growth in localized regions of the gut. We also identified and verified six novel cyst-specific proteins, including new components of the cyst wall that were highly expressed in these foci. Our in vivo transcriptome data support an emerging view that parasites encyst early in localized regions in the gut, possibly as a consequence of nutrient limitation, and also impact local metabolism and physiology.

microbiology↗

bioRxiv2017

Comprehensive Pathway Analyses Of Schizophrenia Risk Loci Point To Dysfunctional Postsynaptic Signaling

Large-scale genome-wide association studies (GWAS) have implicated many low-penetrance loci in schizophrenia. However, its pathological mechanisms are poorly understood, which in turn hampers the development of novel pharmacological treatments. Pathway and gene set analyses carry the potential to generate hypotheses about disease mechanisms and have provided biological context to genome-wide data of schizophrenia. We aimed to examine which biological processes are likely candidates to underlie schizophrenia by integrating novel and powerful pathway analysis tools using data from the largest Psychiatric Genomics Consortium schizophrenia GWAS (N = 79 845) and the most recent 2018 schizophrenia GWAS (N = 105 318). By applying a primary unbiased analysis (Multi-marker Analysis of GenoMic Annotation; MAGMA) to weigh the role of biological processes from the MSigDB database, we identified enrichment of common variants in synaptic plasticity and neuron differentiation gene sets. We supported these findings using MAGMA, Meta-Analysis Gene-set Enrichment of variaNT Associations (MAGENTA) and Interval Enrichment Analysis (INRICH) on detailed synaptic signaling pathways from the Kyoto Encyclopedia of Genes and Genomes (KEGG) and found enrichment in mainly the dopaminergic and cholinergic synapses. Moreover, shared genes involved in these neurotransmitter systems had a large contribution to the observed enrichment, protein products of top genes in these pathways showed more direct and indirect interactions than expected by chance, and expression profiles of these genes were largely similar among brain tissues. In conclusion, we provide strong and consistent genetics and protein-interaction informed evidence for the role of postsynaptic signaling processes in schizophrenia, opening avenues for future translational and psychopharmacological studies.

genetics↗

bioRxiv2017

ModuleDiscoverer: Identification of regulatory modules in protein-protein interaction networks.

The identification of disease associated modules based on protein-protein interaction networks (PPINs) and gene expression data has provided new insights into the mechanistic nature of diverse diseases. A major problem hampering their identification is the detection of protein communities within large-scale, whole-genome PPINs. Current strategies solve the maximal clique enumeration (MCE) problem, i.e., the enumeration of all non-extendable groups of proteins, where each pair of proteins is connected by an edge. The MCE problem however is non-deterministic polynomial time hard and can thus be computationally overwhelming for large-scale, whole-genome PPINs.\n\nWe present ModuleDiscoverer, a novel approach for the identification of regulatory modules from PPINs in conjunction with gene-expression data. ModuleDiscoverer is a heuristic that approximates the community structure underlying PPINs. Based on a high-confidence PPIN of Rattus norvegicus and publicly available gene expression data we apply our algorithm to identify the regulatory module of a rat-model of diet induced non-alcoholic steatohepatitis (NASH). We validate the module using single-nucleotide polymorphism data from independent genome-wide association studies. Structural analysis of the module reveals 10 sub-modules. These sub-modules are associated with distinct biological functions and pathways that are relevant to the pathological and clinical situation in NASH.\n\nModuleDiscoverer is freely available upon request from the corresponding author.

systems biology↗

bioRxiv2017

Polymersomes Targeting Mononuclear Phagocytes

Mononuclear phagocytes such as monocytes, tissue-specific macrophages and dendritic cells are primary actors in both innate and adaptive immunity, as well as tissue homoeostasis. They have key roles in a range of physiological and pathological processes, so any strategy targeting these cells will have wide-ranging impact. These phagocytes can be parasitized by intracellular bacteria, turning them from housekeepers to hiding places and favouring chronic and/or disseminated infection. One of the most infamous is the bacteria that cause tuberculosis, which is the most pandemic and one of the deadliest disease with one third of the worlds population infected, and 1.8 million deaths worldwide in 2015. Here we demonstrate the effective targeting and intracellular delivery of antibiotics to both circulating monocytes and resident macrophages, using pH sensitive nanoscopic polymersomes made of poly(2-(methacryloyloxy)ethyl phosphorylcholine)-co-poly(2-(di-isopropylamino)ethyl methacrylate) (PMPC-PDPA). Polymersome selectivity to mononuclear phagocytes is demonstrated and ascribed to the polymerised phosphorylcholine motifs affinity toward scavenger receptors. Finally, we demonstrate the successful exploitation of this targeting for the effective eradication of intracellular bacteria that cause tuberculosis Mycobacterium tuberculosis as well as other intracellular parasites including the Mycobacterium bovis, Mycobacterium marinum and the most common bacteria associated with antibiotic resistance, the Staphylococcus aureus.

immunology↗

bioRxiv2017

Accurate Cytogenetic Biodosimetry Through Automation Of Dicentric Chromosome Curation And Metaphase Cell Selection

Software to automate digital pathology relies on image quality and the rates of false positive and negative objects in these images. Cytogenetic biodosimetry detects dicentric chromosomes (DCs) that arise from exposure to ionizing radiation, and determines radiation dose received from the frequency of DCs. We present image segmentation methods to rank high quality cytogenetic images and eliminate suboptimal metaphase cell data based on novel quality measures. Improvements in DC recognition increase the accuracy of dose estimates, by reducing false positive (FP) DC detection. A set of chromosome morphology segmentation methods selectively filtered out false DCs, arising primarily from extended prometaphase chromosomes, sister chromatid separation and chromosome fragmentation. This reduced FPs by 55% and was highly specific to the abnormal structures ([≥]97.7%). Additional procedures were then developed to fully automate image review, resulting in 6 image-level filters that, when combined, selectively remove images with consistently unparsable or incorrectly segmented chromosome morphologies. Overall, these filters can eliminate half of the FPs detected by manual image review. Optimal image selection and FP DCs are minimized by combining multiple feature based segmentation filters and a novel image sorting procedure based on the known distribution of chromosome lengths. Applying the same segmentation filtering procedures to both calibration and test sample image data reduced the average dose estimation error from 0.4Gy to <0.2Gy, obviating the need to first manually review these images. This reliable and scalable solution enables batch processing multiple samples of unknown dose, and meets current requirements for triage radiation biodosimetry of high quality metaphase cell preparations.

genetics↗