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PubMed2025

Comprehensive Transcriptome Annotation of Thousands of HIV-1 Genomes.

Alternative splicing in HIV-1 has been a central focus of decades of research, uncovering key mechanisms of viral gene regulation, immune evasion, and therapeutic response - yet, no reference resource has existed to support transcriptome-wide analysis, limiting adoption of modern computational methods. We present HIV Atlas (https://ccb.jhu.edu/HIV_Atlas), the first reference-quality annotation of HIV-1 and SIV transcriptional diversity. We manually curated transcriptomes for HIV-1HXB2 and SIVmac239 and developed Vira, an automated annotation-transfer method specifically designed to address unique challenges of viral genome biology, to generate high-quality annotations for 2,077 complete HIV-1 genomes. Using the resources presented in our work, we evaluated conservation of splice sites, revealing near-perfect preservation of major donors and acceptors. Furthermore, using several public datasets, we demonstrate how HIV Atlas enhances methodology, improves the quality and novelty of results, and opens novel avenues for research, supporting more accurate and comprehensive analyses of bulk, single-cell, and spatial RNA-seq in HIV-1 studies.

Journal Article↗
PubMedDate not supplied

Proportional localization system for anatomical interpretation of cerebral computed tomograms.

The existence of individual variations in size and shape of the human brain constitutes a problem for the anatomical interpretation of brain reconstructed images obtained from scanning devices; it is, for example, responsible for most of the inaccuracies in reading CT scans. One way to account for these variations is to use a proportional localization system. In the 1960s a group of neurosurgeons developed such a system based on two pivotal intracerebral structures, the anterior and the posterior commissures; they published an atlas consisting of horizontal, coronal, and sagittal brain sections interpreted in the proportional system. The atlas also included standard proportional brain schemes based on anatomical and radiological studies on large numbers of individuals. In this article we report a target localization experiment that we carried out to determine if this atlas could be used as a reference for a more accurate interpretation of CT and, eventually, of positron emission tomography (PET) and nuclear magnetic resonance (NMR) scans. Ten radiopaque small targets were inserted through the skull in the cortex of three cadavers; head CT was performed, and the atlas was used for predicting the cortical location of the targets seen on the CT images: The predictions were confirmed. These results strongly support the use of the proportional atlas for the interpretation of CT as well as of PET and NMR scans.

Anatomy, Artistic↗
PubMed1988

[Lateral coordinate of the thalamic Vim neurons in the cases with dilated third ventricle].

Precise radiographical measurement of the third ventricle in the first and essential procedure in stereotaxic surgery in order to determine the target point. This is done while referring to an available standard brain atlas such as Schaltenbrand & Bailey. However there have been no criteria established for determining the deviation of the coordinates of the thalamic nuclei, especially in their lateral coordinates when the third ventricle is highly dilated. Therefore, in 109 cases encountered recently (81 parkinsonism, 11 essential tremor, 10 cerebral palsy, 3 thalamic pain, 1 Benedikt's syndrome, 1 torticollis, 1 oral dyskinesia, 1 striato-nigral degeneration), we studied the correlation between the width of the third ventricle and the lateral coordinate of the thalamic point where kinesthetic neurons or tremor-synchronously discharging neurons were detected. These neurons were especially related to the arm. According to the width of the third ventricle, we classified the cases into three types: 18 cases with large ventricles (more than 10 mm), 37 cases with medium-sized ventricles (4-10 mm) and 16 cases with small ventricles (less than 4 mm). By plotting the lateral coordinate of the thalamic point where kinesthetic neuron of the upper extremity was recorded in reference to the radiogram of anteroposterior view, we found that the lateral coordinates of large ventricular cases generally tended to show more lateral displacement than cases where the ventricles were narrower. Their mean lateral coordinate was 16.9 mm from midline in contrast ot 14.0 mm in cases with small ventricular width. There was a linear correlation between the width of the third ventricle and the lateral coordinate of the kinesthetic neuron of the Vim nucleus.(ABSTRACT TRUNCATED AT 250 WORDS)

Brain Mapping↗
PubMed2025

The new frontier in understanding human and mammalian brain development.

Neurodevelopmental disorders that cause cognitive, behavioural or motor impairments affect around 15% of children and adolescents worldwide1, with diagnoses of profound autism and attention deficit hyperactivity disorder increasing in the USA and contributing to a major economic burden2,3. Yet the origins and mechanisms of these conditions remain poorly understood, limiting progress in therapies. Comprehensive cell atlases of the developing human brain, alongside those of model organisms such as mice and non-human primates, are now providing high-resolution measures of gene expression, cell-type abundance and spatial distribution. In this Perspective, we highlight recent studies that have identified novel developmental cell populations, revealed conserved and divergent patterns of cell genesis, migration and maturation across species, and begun testing hypotheses that link them to processes ranging from transcriptional control of cell fate specification to the emergence of complex behaviours. We present remaining conceptual and technical challenges and provide an outlook on how further studies of human and mammalian brain development can empower a deeper understanding of neurodevelopmental and neuropsychiatric disorders. Future efforts expanding to additional developmental stages, including adolescence, as well as whole-brain, multimodal and cross-species integration, will yield new insights into how development shapes the brain. These atlases promise to serve as essential references for unravelling mechanisms of brain function and disease vulnerability, and for advancing precision medicine.

Humans↗
PubMedDate not supplied

A new method for representing the human anatomy.

In current practice, anatomical atlases are based on a collection of planar images presented in a book or, recently, stored on digital media. We present a new method for generating interactive true three-dimensional (3D) anatomical atlases based on a volume model derived from MRI and CT. The model has a two layer structure. The lower level is a volume model with a set of semantic attributes connected to each voxel. The semantic attributes are assigned by an anatomist using a volume editor. The upper level is a set of relations between these attributes. Interactive visualization tools such as multiple surface display, transparent rendering, and cutting are provided. It is shown that the combination of this data structure with advanced volume visualization tools provides the "look and feel" of real dissection. First tests show that the atlas system cannot only be used successfully for anatomy teaching, but also as a reference for radiologists or surgeons. As a replacement of classical atlases, however, the spatial resolution has still to be improved.

Anatomy↗
PubMed1999

A brainstem stereotactic atlas in a three-dimensional magnetic resonance imaging navigation system: first experiences with atlas-to-patient registration.

OBJECT: The authors describe a computer-resident digital representation of a stereotactic atlas of the human brainstem, its semiautomated registration to sagittal fast low-angle shot three-dimensional (3-D) magnetic resonance (MR) imaging data sets in 27 healthy volunteers and 24 neurosurgical patients, and an analysis of the subsequent transforms needed to refine the initial registration. METHODS: Contour drawings from the atlas, which offer the 70th percentile of variation of anatomical structures, were interpolated into an isotropic 3-D representation. Initial atlas-to-patient registration was based on the fastigium/ventricular floor plane reference system. The quality of the fit was evaluated using superimposition of the atlas and MR images. If necessary, the atlas was tailored to the individual anatomy by using additional transforms. On average, the atlas had to be stretched by 2 to 6% in the three directions of space. Scale factors varied over a broad range from -8 to +19% and the benefit of visual interactive control of the atlas-to-patient registration was evident. Analysis of distances within the pons measured in the midsagittal MR imaging slices and the required scale factors revealed significant correlations that may be used to reduce the amount of user interaction in the coregistration substantially. In 70.6% of the cases, the atlas had to be shifted in a cranial direction along the brainstem axis (in 25.5% of cases 3-4 mm, in 45.1% of cases 1-2 mm). This was due to a more caudal position of the fastigium cerebelli on the MR images compared with the atlas. CONCLUSIONS: This observation, in conjunction with the variability of the height of the fourth ventricle in our MR imaging data (range 6.1-15.2 mm, mean 10.1 mm, standard deviation 1.8 mm) calls into question the role of the fastigium cerebelli as an anatomical landmark for localization within the brainstem.

Anatomy, Artistic↗
PubMed1994

Patient dose in dual x-ray absorptiometry.

Dual x-ray absorptiometry (DXA) provides a convenient, non-invasive method of assessing skeletal bone mineral which is widely used for clinical studies. This report describes a study to estimate the effective dose of radiation (ICRP-60 (1990)) to a typical female patient from scans performed on three DXA scanners: the Hologic QDR-1000, QDR-1000/W and QDR-2000. The scans modes studied were: total body; anteroposterior (AP) lumbar spine; lateral lumbar spine; proximal femur; distal forearm. An ionization chamber and tissue-equivalent phantom were used to determine entrance surface dose and percentage depth-dose curves for each scan mode. Anatomical data from ICRP-23 (Reference Man) and a body section atlas were used to estimate the absorbed dose to each organ in the scan fields. Effective dose was estimated using the ICRP-60 tissue weighting factors and the fraction of each organ in the scan field. Results are summarized below. Figures for the effective dose are given both excluding and (in brackets) including the ovaries to cover the cases of postmenopausal and premenopausal women respectively.

Absorptiometry, Photon↗
PubMed2026

Enhancing pan-cancer spatial transcriptomics at single-cell resolution with stPainter.

Subcellular spatial transcriptomics can resolve tissue architecture at cellular scale, but sparse gene panels and limited detection sensitivity constrain downstream analysis. Existing enhancement methods often require tissue-matched single-cell RNA sequencing (scRNA-seq) references and dataset-specific retraining. Here we show that stPainter, a conditional generative model pretrained on a pan-cancer scRNA-seq atlas, can enhance spatial transcriptomics data without matched references or retraining. Using a latent diffusion architecture guided by Stochastic Differential Equations (SDE), stPainter reconstructs expanded expression profiles from sparse measurements and produces latent representations for clustering and cell-state analysis. When we apply stPainter upon 6 spatial transcriptomics datasets of different cancer types, we demonstrate that our model empowers downstream biological analyses, including fine-grained subpopulation clustering and pathway enrichment. Comparison with spatially resolved proteomics (CODEX) provided independent support for regional agreement between imputed cellular compositions and protein-level tissue organization. These results establish stPainter as a scalable approach for analyzing tumor microenvironments without auxiliary sequencing data.

Spatial Transcriptomics↗
PubMed1994

The quantitative anatomy of the atlas.

STUDY DESIGN: This study is based on direct quantitative caliper measurements of 88 isolated anatomic specimens of the C1 vertebra. OBJECTIVES: The study was undertaken to establish the range and variability of the external dimensions of the atlas and to describe the cortical thicknesses and trabecular distribution of this unique vertebra. SUMMARY OF BACKGROUND DATA: Before this study, Francis in 1952 reported the total anterior and posterior diameter of 285 atlas vertebrae. Liu et al reported detailed external dimensions and facet joint surface morphologies on a total of three C1 vertebrae. METHODS: Measurements were made of overall dimensions, canal diameters, and the dimensions of the anterior and posterior arches of 88 dried human C1 vertebrae. Eight specimens were sectioned in the frontal plane, eight in the sagittal plane, and four in the coronal plane. The anatomy of these sections was documented by radiographic imaging. Cortical thicknesses on the sections were then obtained by direct measurement. RESULTS: The canal diameter ranged from 32 mm (SD 2 mm) in the sagittal plane, and 29 mm (SD 2 mm) in the lateral dimension. The mean thickness of the anterior ring was 6 mm (SD 1 mm) and posteriorly was 8 mm (SD 2 mm). Cortical bone was thinnest posteriorly. CONCLUSIONS: These measurements indicated remarkably constant dimensions for the ring itself, suggesting there may be significant functional restraints on the canal size of this unique vertebra. In contrast, a significant variability was noted in objective measurements of lateral mass height and sagittal plane widths of the entire bone.

Cervical Atlas↗
PubMed2005

On-line automatic slice positioning for brain MR imaging.

In clinical brain MR imaging protocols, the technician collects a quick localizer and manually positions the subsequent scans using the localizer as a guide. We present a method for automatic slice positioning using a rapidly acquired 3D localizer. The localizer is automatically aligned to a statistical atlas representing 40 healthy subjects. The atlas contains the probability of a given tissue type occurring at a given location in atlas space and the conditional probability distribution of the multi-spectral MRI intensity values for a given tissue class. Accurate rigid alignment of each subject to an atlas ensures that all patients' scans are acquired in a consistent manner. A further benefit is that slices are positioned consistently over time, so that scans of patients returning for follow-up imaging can be compared side-by-side to accurately monitor the progression of illness. The procedure also helps ensure that left/right asymmetries reflect true anatomy rather than being the result of oblique slice positioning relative to the underlying anatomy. The use of an atlas-based procedure eliminates the need to refer to a database of previously scanned images of the same patient and ensures corresponding alignment across scanners and sites, without requiring fiducial markers. Since the registration method is probabilistic, the registration error tends to increase smoothly in the presence of increasing noise and unusual anatomy or pathology rather than failing catastrophically. Translations and rotations relative to the atlas can be set so that planning can be done in anatomical space, rather than scanner coordinates, and stored as part of the protocol allowing standardization of slice orientations.

Algorithms↗
PubMed1997

Automatic analysis of cerebral atrophy.

3D MR data obtained for 10 healthy control subjects have been used to build a brain atlas. The atlas is built in four stages. First, a set of features that are unambiguously definable and anatomically relevant need to be computed for each item in the database. The chosen features are crest lines along which the maximal principal curvature of the surface of the brain is maximal in its associated principal direction. Second, a nonrigid registration algorithm is used to determine the common crest lines among the subjects in the database. These crest lines form the structure of the atlas. Third, a set of crest lines is taken as a reference set and a modal analysis is performed to determine the fundamental deformations that are necessary to bring the individual data in line with the reference set. The deformations are averaged and the set of mean crest lines becomes the atlas. Finally, the standard deviation of the deformations between the atlas and the items in the database defines the normal variation in the relative positions of the crest lines in a healthy population. In a fully automatic procedure, the crest lines on the surface of the brain adjacent to the cerebral ventricles in a patient with primary progressive aphasia were compared to the atlas; confirmation that the brain of this patient demonstrates atrophy was provided by stereological analysis that showed that the volume of the left cerebral hemisphere is 48.8 ml (CE 2.8%) less than the volume of the right cerebral hemisphere in the region of the temporal and frontal lobes. When the amplitude of the deformations necessary to register the crest lines obtained for the patient with the atlas were greater than three standard deviations beyond the variability inherent in the atlas, the deformation was considered significant. Four of the main deformation modes of the longest crest line of the surface of the brain adjacent to the cerebral ventricles were significantly different in the patient with primary progressive aphasia compared to the atlas. The ventricles are preferentially enlarged in the left cerebral hemisphere. Furthermore, they are closer together posteriorly and further apart anteriorly than in the atlas. These observations may be indicative of the atrophy of the temporal and frontal lobes of the left cerebral hemisphere noted in the patient. Ultimately, the approach may provide a useful screening technique for identifying brain diseases involving cerebral atrophy. Serial studies of individual patients may provide insights into the processes controlling or affected by particular disease.

Aged↗
PubMed1998

Reference structures for assessment of frontal head posture.

The aim of the study was to test (a) the validity of the supra-orbital line as a substitute for the interpupillary line, and (b) the reproducibility of two different approaches of assessing cranio- and cervico-vertical relationships on frontal cephalograms. The material consisted of natural head position frontal cephalograms of 21 healthy Finnish students and 11 Danish young adults prepared according to a method described previously, modified in the Danish sample by addition of spectacles with a wire to indicate the interpupillary line. The cephalograms were analysed manually twice by two investigators with an interval of one week. The following reference lines were selected: (1) orbital line (ORB): a tangent to the extreme cranial point on the supra-orbital margins; (2) cranial line (CR): the line drawn through crista galli and anterior nasal spine; (3) cervical line (CER): a line drawn through the midpoints of atlas (half the distance between the most median points on the tubercle of the transverse ligament), and C4 (half the distance between the most concave points of the lateral masses); (4) the main course of the upper cervical spine (SPINE): a subjective impression of the spinal inclination; (5) the interpupillary line (IP); and (6) the true vertical and horizontal lines (VER, HOR). The angles were measured to the nearest 0.5 degrees. Intra- and inter-examiner reproducibility was calculated. The supra-orbital line almost coincided with the interpupillary line as the mean inclination between the lines was only 0.5 degrees. Both intra- and inter-examiner errors were less for ORB and CER than for CR and the line indicating the main course of the upper cervical spine (SPINE). The intra-examiner reproducibility s(i) for ORB/HOR and CR/VER was 0.4 and 0.8 degrees respectively, and for CER/VER and SPINE/VER 0.8 degrees and 1.0 degrees. Based on these results, the supra-orbital line and the cervical line (defined as the mid-transversal line between the atlas and the fourth cervical vertebra) are recommended as reference lines for assessing frontal head posture.

Adolescent↗
PubMed1993

Accuracy of ventrolateral thalamic nucleus localization using unreformatted CT scans and the B-R-W system. Experimental studies and clinical findings during functional neurosurgery.

The accuracy with which the ventrolateral thalamic nucleus could be targetted using the BRW stereotactic system and unreformatted axial CT imaging was evaluated in cadaver brains mounted in a skull. Ball bearings (1.82 mm diameter) were placed in the nuclei ventro intermedius (Vim), ventro oralis anterior (Voa) and posterior (Vop) and the brains then sectioned, the locations of the ball bearings relative to the anterior (AC) and posterior commissures (PC) measured and evaluated with reference to a Schaltenbrandt and Bailey stereotactic atlas. Targetting of the ventrolateral thalamic region was frequently accurate (77%) but because of errors in estimation of the AC-PC plane (mean forward angulation of 9 degrees) some ball bearings were placed too deeply in the Fields of and Forel, zona incerta and rostral subthalamic nucleus. Ventrolateral thalamotomy using the BRW stereotactic system and unreformatted axial CT imaging was undertaken in six patients with tremor due to a range of pathologies. The tremor was abolished or altered in four patients whilst no lesion was made in the other two patients since no site that reduced the tremor, could be located. The surgical and clinical implications of this study are discussed.

Diencephalon↗
PubMed2001

NMDA-stimulated Ca2+ uptake into barrel cortex slices of spontaneously hypertensive rats.

The spontaneously hypertensive rat (SHR) is used as a model for attention-deficit hyperactivity disorder (ADHD), since it has behavioural characteristics that resemble the behavioral disturbances of ADHD, namely hyperactivity, failure to sustain attention, and impulsiveness. The aim of this study was to establish whether N-methyl-D-aspartate (NMDA) receptor function was altered in barrel cortex slices of 4- to 6- week-old SHR compared to their normotensive Wistar-Kyoto (WKY) control rats. The barrel cortex was dissected from brain slices corresponding to antero-posterior coordinates 8.7-4.8 mm with reference to the Paxinos and Watson (1986) atlas and divided into rostral, middle, and caudal regions. 45Ca2+ uptake was stimulated by incubating test slices in buffer containing 100 microM NMDA for 2 min at 35 degrees C. Total 45Ca2+ uptake into the entire barrel cortex as well as uptake into all regions of SHR barrel cortex was lower compared to WKY. Basal uptake into the entire barrel cortex as well as uptake into rostral and caudal regions of SHR barrel cortex was lower than WKY but basal uptake into the middle region was the same for both strains. There was no difference between SHR and WKY in NMDA-stimulated 45Ca2+ uptake into barrel cortex slices except for significantly lower NMDA-stimulated uptake into the middle region of SHR barrel cortex compared to WKY. These findings suggest that calcium metabolism is disturbed in the somatosensory cortex of SHR but that NMDA receptor function is not altered.

Animals↗
PubMed1994

An experimental study to evaluate the accuracy of diencephalic and pallidal target localization using the Brown-Roberts-Wells stereotactic system and unreformatted axial GE8800 CT scanning.

An experimental study was undertaken to evaluate the accuracy with which the intercommissural line (IL) length and anterior-posterior commissural (AC-PC) plane could be selected using unreformatted axial CT8800 imaging. Using these reference points, the Schaltenbrandt and Bailey stereotactic atlas and the Brown-Roberts-Wells (BRW) stereotactic system 1.82 mm ball bearings were deposited at selected diencephalic and pallidal targets in cadaver brains. There were errors in both IL length (median 1.5 mm) and AC-PC plane (median forward angulation of 9 degrees) estimation. Ball bearing deposition into large nuclei such as the pulvinar and globus pallidus and those in proximity to the mid IL such as the nuclei ventro oralis anterior (Voa), ventro oralis posterior (Vop) and ventro intermedius (Vim) was generally good; however, localization of the relatively small intralaminar nucleus was poor. This study suggests that when the AC and PC are not well imaged on sagittal reformations of axial diencephalic CT scans estimation of the AC-PC plane and IL from axial CT scans may be accurate enough for anatomical localization of certain functional stereotactic targets. The implications of this experimental study to operative functional stereotaxy are discussed.

Biopsy↗
PubMed1980

New frame for stereotaxic surgery. Technical note.

A new frame designed for stereotaxic surgery allows performance of a one-stage procedure without the need for mathematical calculation or the use of atlases or diagrams. This frame simulates the reference line in the center of the brain with two lines, one on each side of the head (on the frame) parallel and equal in length to the reference line and at equal distance from the midline. Lesions can be made easily and accurately on either or both sides in a one-stage procedure with use of precise data for the target through any specific or pre-existing burr hole.

Humans↗
PubMed2026

GRNContext: an interactive web platform for contextualized gene regulatory networks visualization across human cancers.

SUMMARY: While current Gene Regulatory Network (GRN) databases provide comprehensive reference maps of potential interactions between transcription factors and target genes, they do not specify which regulatory interactions are active within specific biological contexts. This limitation is particularly critical in cancer, where transcriptional programs are inherently tissue-specific. To address this gap, we developed GRNContext, an interactive web platform designed for the visualization, exploration, and comparative analysis of gene regulatory networks contextualized across 33 cancer types from The Cancer Genome Atlas (TCGA). Our approach uses the TFLink human reference GRN as a starting point and integrates TCGA transcriptomic profiles to infer cancer-specific regulatory activity. Regulatory relevance was assessed using complementary machine learning and statistical methods, which were unified into a consensus score to prioritize and filter the most relevant candidate regulators for each target gene. By providing both curated context-specific GRNs and a user-friendly platform, GRNContext constitutes a comprehensive and accessible resource that supports mechanistic investigations, hypothesis generation, and translational research focused on transcriptional regulation in cancer. AVAILABILITY AND IMPLEMENTATION: GRNContext is supported by all major browsers and freely available on the web at https://apps.cienciavida.org/grncontext. It is implemented as a client-server web application featuring a FastAPI backend and a React frontend utilizing Cytoscape.js for interactive network visualization, all containerized via Docker for cross-platform compatibility.

Humans↗
PubMed1994

Assessment of cerebral perfusion with single-photon emission tomography in normal subjects and in patients with Alzheimer's disease: effects of region of interest selection.

The shape, size and location of regions of interest (ROIs) show considerable variability between single-photon emission tomography (SPET) studies in aging and Alzheimer's disease, but the possible influence on study results remains unknown. We compared three different ROIs in a SPET study with 60 controls and in 48 patients with probable Alzheimer's disease diagnosed according to the NINCDS-ADRDA criteria. Regional cerebral blood flow (rCBF) was assessed with SPET using technetium-99m d,l-hexamethylpropylene amine oxime (99mTc-HMPAO), normalized to the mean activity in a cerebellar reference slice. The three different ROIs were: a multi-slice and a single-slice ROI with reference to the normal brain anatomy (using an anatomical atlas), and a rectangular (2 x 4 pixels) ROI in the frontal, temporal, temporoparietal and occipital cortices. No differences were observed for the means of rCBF values between the single-slice and multi-slice ROI's with reference to the normal anatomy, but some variability was present for individual comparisons. In contrast, significantly higher mean rCBF values were obtained with the single-slice rectangular ROIs in all four regions for both patients and controls and considerable variability was shown for individual subjects. After analysis with multivariate logistic regression and receiver operator characteristic curves, the ability of SPET to discriminate between controls and Alzheimer patients was similar in the three methods for mild and moderate Alzheimer patients (Global Deterioration Scale = GDS of 3 and 4). However, with increasing dementia severity (GDS > 4) the rectangular ROIs showed lower ability to discriminate between groups compared to the single-slice and multi-slice anatomically defined ROIs.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗