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Lack of task specificity and absence of posttraining effects of atropine on learning.

Three experiments are reported whose purpose was to examine the effect of the cholinergic antagonist atropine on the acquisition of different learning tasks known to be sensitive or insensitive to impairment by hippocampal lesions; on the retention of performance acquired in the absence of the drug; and on memory consolidation immediately after daily training trials. In Experiment 1, atropine sulfate (10 or 50 mg/kg, ip), injected 30 min prior to training, severely impaired learning of both spatial and nonspatial discrimination tasks when compared with saline or atropine methylnitrate (50 mg/kg). In Experiment 2, atropine sulfate (50 mg/kg) also impaired spatial discrimination accuracy in rats previously trained to asymptote under drug-free conditions. These deficits were not due to either peripheral drug effects or gross sensorimotor impairments. In Experiment 3, daily posttraining injections of atropine sulfate (50 mg/kg) failed to influence either learning or subsequent retention of place navigation in rats that were trained to find a single hidden escape platform. The data confirm that profound learning deficits occur when training is conducted under atropine but offer no support to the hypothesis that cholinergic neurons play an important role in memory consolidation or other posttraining processes. Furthermore, these results point to dissimilarities between the behavioral impairments induced by cholinergic blockade and hippocampal lesions under appropriate test regimes.

Animals↗

Absence of an interaction between navigational strategies based on local and distal landmarks.

In 3 experiments, rats were required to escape from a Morris pool by swimming to a submerged platform that was located at the apex of a notional, equilateral triangle with 2 different landmarks occupying the corners at the base. Training for 1 group was always conducted in view of the landmarks surrounding the pool and with the triangular array in a fixed orientation. Subjects could therefore identify the direction of the platform from a single landmark within the pool by reference to cues outside the pool or to the other landmark within the pool. Both strategies were used, and the results from additional groups revealed that the first of these strategies did not affect the acquisition of the second one.

Animals↗

Single-step analysis of low abundance phosphoamino acids via on-line sample preconcentration with chemical derivatization by capillary electrophoresis.

New strategies for rapid, sensitive and high-throughput analysis of low abundance metabolites in biological samples are required for future metabolomic research. In this report, a direct method for sub-micromolar analyses of phosphoamino acids was developed using on-line sample preconcentration with 9-fluorenylmethyloxycarbonyl chloride (FMOC) derivatization by capillary electrophoresis (CE) and UV detection. Analyte focusing by dynamic pH junction and FMOC labeling efficiency were influenced by several experimental factors including buffer pH, ionic strength, sample injection length and FMOC concentration. About a 200-fold enhancement in concentration sensitivity was achieved under optimal conditions relative to conventional off-line derivatization, as reflected by a detection limit (S/N approximately 3) of 0.1 microM. In-capillary sample preconcentration with chemical labeling by CE offers a unique single-step analytical platform for high-throughput screening of low abundance metabolites without intrinsic chromophores.

Animals↗

Comparison of statistical parametric mapping and SPECT difference imaging in patients with temporal lobe epilepsy.

PURPOSE: Statistical parametric mapping (SPM) is an image-analysis tool that assesses the statistical significance of cerebral blood flow (CBF) changes on a voxel-by-voxel basis, thereby removing the subjectivity inherent in conventional region-of-interest (ROI) analysis. Our platform of single-photon emission computed tomography (SPECT) ictal-interictal difference imaging in clinical epilepsy has been validated for localizing seizure onset. We extend the tools of SPM by further applying statistical measures for the significance of perfusion changes in individual patients to localize epileptogenic foci in patients with defined temporal lobe epilepsy by using paired scans in this preliminary study. METHODS: Twelve patients with pairs of periictal and interictal SPECT scans were analyzed in this comparison study between SPECT difference imaging and SPM difference analysis by using a reference database of paired normal healthy images. These 12 patients possessed seizure foci localized to the mesial temporal lobe as confirmed by surgical outcome and by hippocampal sclerosis on pathology. SPM was used to identify clusters of increased or decreased CBF in each patient in contrast to our control group. RESULTS: The regions having the most significant increased or decreased CBF by SPM analysis were in agreement with regions identified by conventional difference imaging and visual analysis by viewers blinded to the results of the SPM analysis. Differentiated further by time of radiopharmaceutical injection, six of seven patients injected within 100 s of seizure onset displayed hyperperfusion changes localized to the corresponding epileptogenic temporal lobe by both techniques. Among patients receiving injections after 100 s, both techniques showed primarily regions of hypoperfusion, which again were similar between these two methods. CONCLUSIONS: The results provide strong evidence supporting SPM difference analysis in assessing regions of significant CBF change from baseline in concordance with our current clinically used technique of SPECT ictal--interictal difference imaging in epilepsy patients. Difference analysis using SPM could serve as a useful diagnostic tool in the evaluation of seizure focus in temporal lobe epilepsy.

Adolescent↗

MitoTracer facilitates the identification of informative mitochondrial mutations for precise lineage reconstruction.

Mitochondrial (MT) mutations serve as natural genetic markers for inferring clonal relationships using single cell sequencing data. However, the fundamental challenge of MT mutation-based lineage tracing is automated identification of informative MT mutations. Here, we introduced an open-source computational algorithm called "MitoTracer", which accurately identified clonally informative MT mutations and inferred evolutionary lineage from scRNA-seq or scATAC-seq samples. We benchmarked MitoTracer using the ground-truth experimental lineage sequencing data and demonstrated its superior performance over the existing methods measured by high sensitivity and specificity. MitoTracer is compatible with multiple single cell sequencing platforms. Its application to a cancer evolution dataset revealed the genes related to primary BRAF-inhibitor resistance from scRNA-seq data of BRAF-mutated cancer cells. Overall, our work provided a valuable tool for capturing real informative MT mutations and tracing the lineages among cells.

Journal Article↗

Verification of an assay for quantification of hepatitis C virus RNA by use of an analyte-specific reagent and two different extraction methods.

Protocols were designed for quantification and detection of hepatitis C virus (HCV) RNA by the use of an analyte-specific reagent (ASR) (Roche COBAS TaqMan48 [CTM48] HCV) after manual and automated RNA extraction. The purposes were to determine (i) assay performance characteristics using manual and automated RNA extraction methods, (ii) whether measurable range and limit of detection (LOD) of the ASR assay were influenced by genotype, and (iii) correlation of quantification by CTM48 HCV ASR and COBAS Monitor HCV v. 2.0. For HCV genotype 1 (Gt1), the lower limits of quantification after manual extraction were slightly lower than those for automated extraction (1.0 versus 1.5 log(10) IU/ml). Results were linear up to the highest concentration tested after extraction by both methods (manual, 6.1 log(10); automated, 6.4 log(10)). Similar results were obtained for Gt2 (1.8 to 6.8 log(10) IU/ml) and Gt3 (1.6 to 6.8 log(10) IU/ml) after automated extraction. The LOD of Gt1 virus was 10 IU/ml after manual extraction and between 25 and 37.5 IU/ml after automated extraction. Results with Gt2 and Gt3 viruses were similar after automated extraction (Gt2, between 25 and 50 IU/ml; Gt3, 25 IU/ml). Variability (intrarun and interrun, at concentrations throughout the range of quantification) was </=13% for both extraction methods. Clinical specimens tested by Monitor were quantified using the CTM48 HCV ASR assay. Characteristics of the regression line included a slope of 0.98 and y intercept of -0.23. Quantification by the two methods was correlated (r = 0.97). CTM48 HCV ASR assay values were on average twofold lower than those for Monitor HCV v. 2.0. These data suggest that our assay combines the characteristics of qualitative and quantitative PCR platforms into a single test.

Automation↗

TNFalpha polymorphisms and risk of psoriatic arthritis.

BACKGROUND: Tumour necrosis factor alpha (TNFalpha) is a cytokine of critical importance in psoriatic arthritis. OBJECTIVES: (1) To examine the association between TNFalpha promoter gene polymorphisms and psoriatic arthritis in two well characterised Canadian populations with the disease; (2) to carry out a meta-analysis of all TNFalpha association studies in white psoriatic arthritis populations. METHODS: DNA samples were genotyped for five TNF variants by time of flight mass spectrometry using the Sequenom platform. All five single nucleotide polymorphisms were in the 5' flanking region of TNFalpha gene at the following positions: -1031 (T-->C), -863 (C-->A), -857 (C-->T), -308 (G-->A), and -238 (G-->A). Primary analyses were based on logistic regression. Summary estimates of disease/genotype relations from several studies were derived from random effects meta-analyses. RESULTS: 237 psoriatic arthritis subjects and 103 controls from Newfoundland and 203 psoriatic arthritis subjects and 101 controls from Toronto were studied. A combined analysis of data from both populations, showed a significant association between disease status and the -238(A) variant (p=0.01). The meta-analysis estimate for the -238(A) TNFalpha variant in eight psoriatic arthritis populations was also significant (odds ratio=2.29 (95% confidence interval, 1.48 to 3.55)). CONCLUSIONS: Analysis of TNFalpha variants in psoriatic arthritis populations shows that the -238 (A) variant is a significant risk factor for this disease.

Arthritis, Psoriatic↗

High resolution microarray comparative genomic hybridisation analysis using spotted oligonucleotides.

BACKGROUND: Currently, comparative genomic hybridisation array (array CGH) is the method of choice for studying genome wide DNA copy number changes. To date, either amplified representations of bacterial artificial chromosomes (BACs)/phage artificial chromosomes (PACs) or cDNAs have been spotted as probes. The production of BAC/PAC and cDNA arrays is time consuming and expensive. AIM: To evaluate the use of spotted 60 mer oligonucleotides (oligos) for array CGH. METHODS: The hybridisation of tumour cell lines with known chromosomal aberrations on to either BAC or oligoarrrays that are mapped to the human genome. RESULTS: Oligo CGH was able to detect amplifications with high accuracy and greater spatial resolution than other currently used array CGH platforms. In addition, single copy number changes could be detected with a resolution comparable to conventional CGH. CONCLUSIONS: Oligos are easy to handle and flexible, because they can be designed for any part of the genome without the need for laborious amplification procedures. The full genome array, containing around 30000 oligos of all genes in the human genome, will represent a big step forward in the analysis of chromosomal copy number changes. Finally, oligoarray CGH can easily be used for any organism with a fully sequenced genome.

Breast Neoplasms↗

UK NEQAS for leucocyte immunophenotyping: the first 10 years.

In the past decade, cellular immunophenotyping has become a new discipline in diagnostic haematology and immunology, and is invaluable in the rapid diagnosis of leukaemia and monitoring disease progression in human immunodeficiency virus infected individuals. The introduction of bench top flow cytometers has meant that immunophenotyping is now also used for the quantitation of CD34(+) peripheral blood stem cells (PBSCs) to ensure the correct timing and adequacy of haematopoietic progenitor cell harvests. Furthermore, flow cytometry has become an important tool for the counting of leucocytes in blood components after leucocyte depletion. Because this new discipline is now such a major diagnostic and prognostic tool in the clinical arena, its use must be subject to both internal and external quality control. Such a requirement was first recognised as early as 1986 when an Inter-Regional Quality Assessment Scheme (IRQAS) was initiated for laboratories that undertook the immunocytochemical diagnosis of leukaemia using the alkaline phosphates anti-alkaline phosphatase technique. This programme began with around 25 UK laboratories. In 1990, after the introduction of two more programmes (one for leukaemia diagnosis using UV microscopy and latterly flow cytometry, and one for the enumeration of CD4(+) T cells) the IRQAS achieved UK National External Quality Assessment Scheme (UK NEQAS) status and changed its title to UK NEQAS for Leucocyte Immunophenotyping. In the past decade the once small IRQAS programme has evolved into the largest international scheme of its kind, providing EQA to over 650 laboratories world wide for leukaemia immunophenotyping, lymphocyte subset analysis, PBSCs, and more recently low level leucocyte counting. Over the years, this EQA programme has highlighted important problems, such as the inappropriate use of fluorochromes and antibody titre, and the identification of effective gating strategies, all of which have contributed directly to the high interlaboratory variations seen in cellular immunophenotyping. Furthermore, particularly in absolute counting of lymphocyte subsets, PBSCs, and the enumeration of low numbers of leucocytes, UK NEQAS for Leucocyte Immunophenotyping programmes have been instrumental in highlighting the differences that occur between single and dual platform flow cytometric technologies. As a result of these findings, UK NEQAS for Leucocyte Immunophenotyping has helped to reduce the variation seen on an interlaboratory basis and enabled greater standardisation both in the UK and internationally. These advances have been attributable to the development, by UK NEQAS for Leucocyte Immunophenotyping, of a unique whole blood stabilising process that ensures the retention of the physical characteristics (both light scatter and antigenic profile) required of cells to ensure successful cellular immunophenotyping. This major technological advancement has enabled the distribution of specimens for EQA purposes on a global scale that have minimal matrix effect and behave in a manner identical to fresh blood for several months after stabilisation.

Antigens, CD34↗

An expression-based site of origin diagnostic method designed for clinical application to cancer of unknown origin.

Gene expression profiling offers a promising new technique for the diagnosis and prognosis of cancer. We have applied this technology to build a clinically robust site of origin classifier with the ultimate aim of applying it to determine the origin of cancer of unknown primary (CUP). A single cDNA microarray platform was used to profile 229 primary and metastatic tumors representing 14 tumor types and multiple histologic subtypes. This data set was subsequently used for training and validation of a support vector machine (SVM) classifier, demonstrating 89% accuracy using a 13-class model. Further, we show the translation of a five-class classifier to a quantitative PCR-based platform. Selecting 79 optimal gene markers, we generated a quantitative-PCR low-density array, allowing the assay of both fresh-frozen and formalin-fixed paraffin-embedded (FFPE) tissue. Data generated using both quantitative PCR and microarray were subsequently used to train and validate a cross-platform SVM model with high prediction accuracy. Finally, we applied our SVM classifiers to 13 cases of CUP. We show that the microarray SVM classifier was capable of making high confidence predictions in 11 of 13 cases. These predictions were supported by comprehensive review of the patients' clinical histories.

Gene Expression Profiling↗

Endovascular microcoil gene delivery using immobilized anti-adenovirus antibody for vector tethering.

BACKGROUND AND PURPOSE: Endovascular microcoils are widely used in interventional procedures to treat cerebral aneurysms. In the present study we report for the first time successful use of an endovascular microcoil as a gene delivery system. METHODS: Anti-adenoviral monoclonal antibodies were covalently attached to the collagen-coated surface of either platinum or polyglycolic acid microcoils. These antibodies were used to tether replication-deficient adenovirus (Ad-GFP [encoding green fluorescent protein] or Ad-LacZ [encoding beta-galactosidase]). Cell culture studies with rat arterial smooth muscle cells (A10) assessed transduction on or near the coil. Platinum coils coated with Ad-GFP were implanted into the ligated common carotid artery (CCA) of adult rats in a model of arterial stasis and pressurization. After 7 days, CCA segments were harvested, and coils were removed for histopathology and GFP expression studies, while organs were evaluated by polymerase chain reaction to assess viral biodistribution. RESULTS: In cell culture studies, GFP-positive smooth muscle cells were detected only on the platinum coil surface, while LacZ-positive cells were detected only on the polyglycolic acid coil surface, thus demonstrating localized gene delivery. After 7-day implantation, GFP (according to fluorescence microscopy and confirmed with immunohistochemistry) was detected on the harvested platinum coil and in the organizing thrombus within the CCA but not in the arterial wall. Morphometric analyses revealed that 13.3+2.0% of cells within the organized thrombus were transduced with Ad-GFP via the gene delivery system. However, arterial smooth muscle cells were negative for GFP according to fluorescence microscopy and immunohistochemistry. Ad-GFP was not detectable by polymerase chain reaction in lung, liver, or kidney. CONCLUSIONS: It is concluded that catheter deployment of platinum or biodegradable gene delivery endovascular microcoils represents an interventional device-based gene therapy system that can serve as a suitable platform for either single or multiple gene therapy vectors.

Adenoviridae↗

Characterization of METTL3/14-mediated m6A modification in human transcriptome using Nanopore direct RNA sequencing.

Post-transcriptional RNA modifications modulate diverse aspects of RNA metabolism. N6-methyladenosine (m6A), one of the most abundant internal RNA modifications, is deposited by the core methyltransferase complex, METTL3 and METTL14. Oxford Nanopore Technologies (ONT) platform permits direct, single RNA molecule sequencing while preserving native modifications. However, without rigorous benchmarking, the accuracy and reproducibility of modification detection remain uncertain. Here, we leveraged ONT to comprehensively profile bona fide m6A modifications in cellular RNAs at single-nucleotide resolution by integrating two direct RNA sequencing chemistries (RNA002 and RNA004) with the m6Anet and Dorado modification-detection models. We independently depleted METTL3 and METTL14 in human cells and rigorously validated modification calls through several assays and independent orthogonal methods (GLORI and miCLIP). We find that Dorado detected a higher number of m6A events and enabled simultaneous detection of other RNA modifications (5-methylcytosine, pseudouridine, and inosine). Pairing Dorado with an in vitro transcribed, unmodified control under stringent filtering, we provide compelling evidence supporting a global reduction in m6A sites and stoichiometry within coding sequences and across genes, particularly in highly modified genes and sites, and at consensus DRACH motifs. We report a differential and complex regulation of modified transcripts, accompanied by a global reduction in poly(A) tail length. Notably, METTL3 and METTL14 depletion produced distinct transcript-specific effects, supporting non-redundant roles within the m6A writer complex. Together, our study illustrates a notable advancement of ONT capabilities and establishes a robust transcriptome-wide framework for RNA modification detection, thereby laying the groundwork for exploring the contribution of METTL3/METTL14 to cellular functions and disease.

Humans↗

[A novel method for fabrication of tissue microarray].

BACKGROUND & OBJECTIVE: Tissue chip (tissue microarray, TMA) is one of the most important biochip techniques, just following the gene chip and the protein chip, which is one of the most important functional genomics and proteomics research methods in the post-genomic era. However, the present TMA technology has certain shortcomings, such as lack of advanced instruments, tedious procedure, and low sampling accuracy, etc. This new method was designed to improve the technology of TMA. METHODS: A common microscope was installed with a special holing needle, a sampling needle, and a proper box to fix paraffin blocks on the microscope carrier. With the precise mechanical control of microscope, the holing procedure on the recipient paraffin blocks and sampling procedure of core tissue biopsies were performed with the re-equipped microscope. The precise observation and localization of sampling regions were also performed using the same microscope equipped with a stereoscope. RESULTS: The new method simplified TMA procedure, and the whole process of holing, locating, and sampling was performed with the same instrument on the same platform. The single-use holing and sampling needles were first applied to maintain higher accuracy and to avoid the tissue remains and contamination among different samples. And high-qualified tissue chips of colorectal tumors were produced successfully by the new method. CONCLUSION: Using the re-equipped common microscope to fabricate tissue microarrays is a simple, reliable, cost-effective,and well-applicable technique.

Histocytological Preparation Techniques↗

[Endovascular microcoil applied for gene delivery system].

OBJECTIVE: To explore the possibility of using an endovascular microcoil as a gene delivery system. METHODS: Anti-adenoviral monoclonal antibodies were covalently attached to the collagen-coated surface of platinum microcoil. These antibodies were used to tether adenovirus encoding green fluorescent protein (Ad-GFP). Cell culture studies with rat arterial smooth muscle cells (A10) assessed transduction on or near the coil. Platinum coils coated with Ad-GFP were implanted into the ligated common carotid artery (CCA) of adult rats in a model of arterial stasis and pressurization. After 7 days, CCA segments were harvested, and coils were removed for histopathology and GFP expression studies, while organs were evaluated by polymerase chain reaction to assess viral biodistribution. RESULTS: In cell culture studies, GFP-positive smooth muscle cells were detected only on the platinum coil surface. After 7 days, GFP was detected on the harvested platinum coil and in the organizing thrombus within the CCA according to fluorescence microscopy and immunohistochemistry. Morphometric analyses revealed that (13.3 +/- 2.0)% of cells within the organized thrombus were transduced with Ad-GFP via the gene delivery system. Ad-GFP was not detectable by polymerase chain reaction in lung, liver, or kidney. CONCLUSIONS: Gene delivery endovascular microcoils represents an interventional device-based gene therapy system that can serve as a suitable platform for either single or multiple gene therapy vectors.

Adenoviridae↗

Vertical loading rates in clinically normal dogs at a trot.

Present data describe the rates of vertical loading and unloading generated by clinically normal dogs in a trotting gait. Forward velocity was found to influence maximal rates of limb loading and unloading in forelimbs and hind limbs. The rates increased as the velocity of the dog/handler increased. The position of maximal limb loading during the stance phase was independent of velocity in the forelimbs, but in the hind limbs, as velocity increased, the position of maximal unloading occurred earlier in the stance phase. Within velocity groups, the forelimbs had greater rates of vertical loading and unloading than did hind limbs. The position at which maximal loading occurred was earlier in the forelimbs than in the hind limbs. There was a difference in the position of maximal unloading between forelimbs and hind limbs, with the forelimbs unloading earlier in the stance phase. Difference between paired forelimbs or paired hind limbs was not found for any measurement within any group. Calculation of loading and unloading rates provides another method of examining functional limb loading in dogs. This method of analysis can be adapted to any animal gaited across a force platform in which single limb strides can be recorded. Calculations can also be done in any axis of measurement. Data indicated loading and unloading rates to be consistent and easily determined, Use of data generated from rates of limb loading can be classified into 2 areas: documentation of acceptance of load by the limb, and indirect measurement of functional stresses placed on bones of the appendicular skeleton.

Animals↗

A scalable, low-cost, sample hashing workflow for multiomic single-cell analysis using the Seq-Well S3 platform.

In-depth analyses of clinical samples have the potential to provide unparalleled insights into the cellular mechanisms that underlie both health and disease, as well as therapeutic and prophylactic responses. However, these specimens are often paucicellular, necessitating the use of workflows that maximize the amount of information that can be learned. Here we provide a detailed protocol for generating and analyzing single-cell multiomic data from low-input samples with the Seq-Well S3 platform. We further describe a matched pipeline for sample hashing that reduces costs and sources of technical variation in the resulting data while also enhancing throughput. In brief, our streamlined and efficient methodology involves: (1) optionally staining single-cell suspensions with antibody-oligonucleotide conjugates for cell surface protein quantification and/or sample multiplexing; (2) generating Seq-Well S3 sequencing libraries; (3) optionally producing bulk-RNA sequencing libraries via SMART-seq2 to support genetic demultiplexing; and (4) computationally analyzing the resulting data. Each step herein has been designed to leverage readily available reagents and standard laboratory equipment, substantially lowering barriers to entry for researchers. The overall Protocol can yield high-quality multiomic insights from samples in under a week.

Single-Cell Analysis↗

Immunospecific reduction of antioligonucleotide antibody-forming cells with a tetrakis-oligonucleotide conjugate (LJP 394), a therapeutic candidate for the treatment of lupus nephritis.

A discrete tetravalent conjugate, 7a (LJP 394), consisting of four oligonucleotides attached to a common carrier or platform was prepared. Single-stranded oligonucleotide 20-mers consisting of alternating deoxycytidine-deoxyadenosine nucleotides, (CA)10, were attached to a tetrabromoacetylated platform by displacement with sulfhydryl-terminated linkers. The tetrabromoacetylated platform 3a was synthesized in three steps using triethylene glycol bis-(chloroformate). The single-stranded conjugate was characterized by polyacrylamide gel electrophoresis, DNA sequencing, phosphate analysis, carbon and nitrogen combustion analysis, and correlation of stoichiometry to conversion in the conjugation process. HPLC and capillary electrophoretic methods were developed to evaluate purity. The tetrakis, single-stranded conjugate was annealed with a stoichiometric amount of a complementary single-stranded oligonucleotide 20-mer consisting of alternating thymidine-deoxyguanosine nucleotides, (TG)10. The double-stranded conjugate LJP 394 was characterized by melt temperature and hyperchromicity, phosphate analysis, and carbon and nitrogen combustion analysis. LJP 394 inhibits binding of DNA to anti-double-stranded oligonucleotide antibodies and reduces anti-oligonucleotide-specific plaque (antibody)-forming cells in an immunized mouse model by a proposed mechanism involving cross-linking B cell surface immunoglobins.

Animals↗

Computational systems analysis of developmental toxicity: design, development and implementation of a Birth Defects Systems Manager (BDSM).

Birth defects and developmental disabilities remain an important public health issue worldwide. With the availability of genomic sequences from a growing number of human and model organisms and the rapid expansion of the public repositories holding large-scale gene expression datasets, a computational systems analysis of developmental toxicology can incorporate this vast digital information toward the realization of predictive models for complex disease. Here we describe the initial design, development and implementation of a Birth Defects Systems Manager (BDSM). The project was motivated by the need for a computational-bioinformatics infrastructure to manage vast digital information from functional genomics and for a new knowledge environment specifically engineered for the analysis of developmental processes and toxicities. Proof-of-concept tested BDSM using meta-analysis of gene expression data collected from different laboratories, technology platforms, and study models. The composite dataset incorporated 232 microarray comparisons of RNA samples by single or dual microarray platforms, cDNA or oligonucleotide based probes, and human or mouse sequence information. Preliminary results identified system-level features in the embryonic transcriptome as it reacted to various developmental-teratological stimuli. BDSM is open access through the worldwide web (http://systemsanalysis.louisville.edu/) and can be integrated with other bioinformatics tools and resources to advance the pace of discovery in birth defects research.

Animals↗