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PubMed2025

Alevin-fry-atac enables rapid and memory frugal mapping of single-cell ATAC-seq data using virtual colors for accurate genomic pseudoalignment.

SUMMARY: Ultrafast mapping of short reads via lightweight mapping techniques such as pseudoalignment has significantly accelerated transcriptomic and metagenomic analyses with minimal accuracy loss compared to alignment-based methods. However, applying pseudoalignment to large genomic references, like chromosomes, is challenging due to their size and repetitive sequences. We introduce a new and modified pseudoalignment scheme that partitions each reference into "virtual colors." These are essentially overlapping bins of fixed maximal extent on the reference sequences that are treated as distinct "colors" from the perspective of the pseudoalignment algorithm. We apply this modified pseudoalignment procedure to process and map single-cell ATAC-seq data in our new tool alevin-fry-atac. We compare alevin-fry-atac to both Chromap and Cell Ranger ATAC. Alevin-fry-atac is highly scalable and, when using 32 threads, is 2.8 times faster than Chromap (the second fastest approach) while using only 33% of the memory required by Chromap. The resulting peaks and clusters generated from alevin-fry-atac show high concordance with those obtained from both Chromap and the Cell Ranger ATAC pipeline, demonstrating that virtual color-enhanced pseudoalignment directly to the genome provides a fast, memory-frugal, and accurate alternative to existing approaches for single-cell ATAC-seq processing. The development of alevin-fry-atac brings single-cell ATAC-seq processing into a unified ecosystem with single-cell RNA-seq processing (via alevin-fry) to work toward providing a truly open alternative to many of the varied capabilities of CellRanger. AVAILABILITY AND IMPLEMENTATION: Alevin-fry-atac is written in Rust and C++17, and is freely-available under a BSD 3-clause license. It is integrated into piscem (https://github.com/COMBINE-lab/piscem) and alevin-fry (https://github.com/COMBINE-lab/alevin-fry), and is also supported directly as part of simpleaf (https://github.com/COMBINE-lab/simpleaf).

Single-Cell Analysis↗
PubMed1991

Functional reorganization of adult cat somatosensory cortex is dependent on NMDA receptors.

We studied effects of selective blockade of N-methyl-D-aspartate (NMDA) receptors in the primary somatosensory cortex (SI) of the adult cat on reorganization of cortical maps after selective deafferentation. About two weeks after hindlimb deafferentation, cortical loci representing the 'trunk' seemingly expanded and 'migrated' into areas originally devoted to the 'hindlimb'. Selective blockade of NMDA receptors of the SI cells by continuous infusion of 2-amino-5-phosphonovalerate (APV) into the cortex disrupted such change. The APV treatment also depressed responses of SI cells to natural sensory stimulation, but left no long-lasting side effects. The results suggest that the processes of map reorganization take place within the SI and involve mechanisms dependent on NMDA-receptor-mediated activity.

2-Amino-5-phosphonovalerate↗
PubMedDate not supplied

Patching. Restitching business portfolios in dynamic markets.

In turbulent markets, businesses and opportunities are constantly falling out of alignment. New technologies and emerging markets create fresh opportunities. Converging markets produce more. And of course, some markets fade. In this landscape of continuous flux, it's more important to build corporate-level strategic processes that enable dynamic repositioning than it is to build any particular defensible position. That's why smart corporate strategists use patching, a process of mapping and remapping business units to create a shifting mix of highly focused, tightly aligned businesses that can respond to changing market opportunities. Patching is not just another name for reorganizing; patchers have a distinctive mindset. Traditional managers see structure as stable; patching managers believe structure is inherently temporary. Traditional managers set corporate strategy first, but patching managers keep the organization focused on the right set of business opportunities and let strategy emerge from individual businesses. Although the focus of patching is flexibility, the process itself follows a pattern. Patching changes are usually small in scale and made frequently. Patching should be done quickly; the emphasis is on getting the patch about right and fixing problems later. Patches should have a test drive before they're formalized but then be tightly scripted after they've been announced. And patching won't work without the right infrastructure: modular business units, fine-grained and complete unit-level metrics, and companywide compensation parity. The authors illustrate how patching works and point out some common stumbling blocks.

Commerce↗
PubMed1993

ODS: ordering DNA sequences--a physical mapping algorithm based on simulated annealing.

In the program ODS we provide a methodology for quickly ordering random clones into a physical map. The process of ordering individual clones with respect to their position along a chromosome is based on the similarity of binary signatures assigned to each clone. This binary signature is obtained by hybridizing each clone to a panel of oligonucleotide probes. By using the fact that the amount of overlap between any two clones is reflected in the similarity of their binary signatures, it is possible to reconstruct a chromosome by minimizing the sum of linking distances between an ordered sequence of clones. Unlike other programs for physical mapping, ODS is very general in the types of data that can be utilized for chromosome reconstruction. Any trait that can be scored in a presence--absence manner, such as hybridized synthetic oligonucleotides, restriction endonuclease recognition sites or single copy landmarks, can be used for analysis. Furthermore, the computational requirements for the construction of large physical maps can be measured in a matter of hours on work-stations such as the VAX2000.

Algorithms↗
PubMed2001

Human glycosaminoglycan glucuronyltransferase I gene and a related processed pseudogene: genomic structure, chromosomal mapping and characterization.

Here we describe the characterization of the human glycosaminoglycan glucuronyltransferase I gene (GlcAT-I) and a related pseudogene. The GlcAT-I gene was localized to human chromosome 11q12-q13 by in situ hybridization of metaphase chromosomes. GlcAT-I spanned 7 kb of human genomic DNA and was divided into five exons. Northern blot analysis showed that GlcAT-I exhibited ubiquitous but markedly different expressions in the human tissues examined. The GlcAT-I promoter was approx. 3-fold more active in a melanoma cell line than in a hepatoma cell line, providing evidence for the differential regulation of the gene's expression. Stepwise 5' deletions of the promoter identified a strong enhancer element between -303 and -153 bp that included binding motifs for Ets, CREB (cAMP-response-element-binding protein) and STAT (signal transducers and activators of transcription). Screening of a human genomic library identified one additional distinct genomic clone containing an approx. 1.4 kb sequence region that shared an overall 95.3% nucleotide identity with exons 1-5 of GlcAT-I. However, a lack of intron sequences, as well as the presence of several nucleotide mutations, insertions and deletions that disrupted the potential GlcAT-I reading frame, suggested that the clone contained a processed pseudogene. The pseudogene was localized to chromosome 3. The human genome therefore contains two related GlcAT-I genes that are located on separate chromosomes.

Base Sequence↗
PubMed1990

Problems and pitfalls in the performance and interpretation of color Doppler flow imaging: observations based on the influences of technical and physiological factors on the color Doppler examination of mitral regurgitation.

Color Doppler flow imaging has become an integral part of the echocardiographic examination. By providing real-time, two-dimensional spatial maps of normal and abnormal cardiac blood flows, this technique provides important information that may be used to guide patient management. The acquisition and display of color Doppler flow information may be influenced by technical factors, by the physiological condition of the patient, by abnormalities of cardiac morphology, and, on occasion, by artifact. In this article, the results of a study performed to evaluate the influence of technical factors on the color Doppler assessment of mitral regurgitation are reported. Mitral regurgitation jet area size changed significantly with variation in the control settings for color gain, color process, color map, color image resolution, and sector width. A review of those factors that influence the performance and interpretation of the color Doppler flow examination is provided and their significance discussed.

Echocardiography, Doppler↗
PubMed1985

DNA-mediated transfer of human melanoma cell surface glycoprotein gp130: identification of transfectants by erythrocyte rosetting.

DNA sequences encoding a human melanoma membrane-bound sialoglycoprotein of 130,000 molecular weight (gp130) were introduced into a clonal derivative of mouse B-16 melanoma cells with the selectable neomycin resistance gene (aminoglycoside phosphotransferase). Mouse transfectants were identified by a rapid and precise screening method with mouse monoclonal antibodies and erythrocyte rosetting. The frequency of gp130 transfectants was approximately 1 in 2,000 to 5,000 colonies with neo+ cells. Analysis of secondary mouse transfectants has revealed that the transfected gp130 has a molecular weight, isoelectric point, intracellular processing, peptide map, and spatial orientation of surface-exposed epitopes indistinguishable from those seen with gp130 from human melanoma cells. In contrast to primary transfectants, secondary transfectants expressing gp130 lack demonstrable human repetitive sequences.

Animals↗
PubMed2002

False memories of the future: a critique of the applications of probabilistic reasoning to the study of cognitive processes.

The authors argue that the ways in which people-scientists and laymen-use probabilistic reasoning is predicated on a set of often questionable assumptions that are implicit and frequently go untested. They relate to the correspondence between the terms of a theory and the observations used to validate the theory and to the implicit understandings of intention and prior knowledge that arise between the conveyer and the receiver of information. The authors show several ways in which the use of probabilistic reasoning rests on a priori commitments to a partitioning of an outcome space and demonstrate that there are many more assumptions underlying the use of probabilistic reasoning than are usually acknowledged. They unfold these assumptions to show how several different interpretations of the same results in behavioral decision theory and cognitive psychology are equally well supported by "the facts." They then propose a more comprehensive approach to mapping cognitive processes than those currently used, one that is based on the analysis of all of the relevant alternative interpretations presented in the article.

Cognition↗
PubMedDate not supplied

Comparison of MultiMap and TSP/CONCORDE for constructing radiation hybrid maps.

Radiation hybrid (RH) map construction allows investigators to locate both type I and type II markers on a given genome map. The process is composed of two steps. The first consists of determining the pattern distribution of a set of markers within the different cell lines of an RH panel. This is mainly done by polymerase chain reaction (PCR) amplification and gel electrophoresis, and results in a series of numbers indicating the presence or the absence of each marker in each cell line. The second step consists of a comparison of these numbers, using various algorithms, to group and then order markers. Because different algorithms may provide (slightly) different orders, we have compared the merits of the MultiMap and TSP/CONCORDE packages using a data set of information currently under analysis for construction of the canine genome RH map.

Animals↗
PubMed2002

How to make mapping images of biological specimens--data collection and image processing.

To make high-quality elemental mapping images of biological specimens, the conditions of data collection were optimized, and image-processing methods were examined. The most important step was to obtain a sufficient number of electrons to make the images. The exposure time was limited by the characteristics of the CCD camera. Obtaining a long exposure time exceeded the limitations of the camera, so exposures of the same area were performed many times and recorded in many images. The divided images were merged after observation. To merge images, a new software, 'Rotate & Merge' (R&M), was developed. Because of the characteristics of biological specimens, R&M must have several functions. Picture-zoom and image rotation are necessary because of shrinkage of the specimens due to irradiation during exposure, since even cryo techniques, including low-dose techniques, do not prevent shrinkage of specimens. Merged phosphorus-mapping images of ultra-thin slices of yeast cells were made. In these images, ribosome particles and DNA in the nucleus were observed clearly. The merging was very useful for improving the quality of mapping images.

Cyanobacteria↗
PubMedDate not supplied

Low-dimensional chaos maps learning in a model neuropil (olfactory bulb).

Quantification of a chaotic system can be made by calculating the correlation dimension (D2) of the data that the system generates (Packard et al., 1980). The D2 algorithm, however, requires stationarity of the generator, a feature that biological data rarely reflect (Mayer-Kress et al., 1988). So we developed the "point correlation dimension" (PD2), an algorithm that accurately tracks D2 in linked data of different dimensions (Carpeggiani et al., 1991). We now present a mathematical argument that, for stationary data, individual PD2s converge to D2 and we demonstrate that the algorithm rejects contributions made by bursts of noise. Data were obtained from the surface of the olfactory bulb of the conscious rabbit (64 electrodes, 640 Hz each, 1.3 sec epochs) before and after presentation of a novel or habituated odor. D2 could be calculated in only 1 of 10 novel-odor trials, whereas PD2 could be calculated in all. Both algorithms indicated that a novel odor evokes a spatially uniform dimensional increase. The PD2 uniquely exhibited the dimensional decreases that occur during inspiration and the gradients of mean dimension present during the nonstimulated control state. These control gradients remained unchanged without odor experience, but showed spatially specific PD2 increases following odor habituation. It is interpreted that, 1) the PD2 is sensitive, accurate, and appropriate for dimensional assessment of biological data, 2) that during analysis of unfamiliar information a single global process is transiently evoked in the neuropil, and 3) after experience multiple spatially specific processes tonically map the sites of learning.

Algorithms↗
PubMedDate not supplied

Basic level object categories support the acquisition of novel adjectives: evidence from preschool-aged children.

Two experiments examined 3- and 4-year-old children's ability to map novel adjectives to object properties. Sixty-four children were introduced to a target (e.g., a bumpy object), and asked to choose between (1) a matching test object (e.g., a different bumpy object), and (2) a contrasting test object (e.g., a smooth object). Four-year-olds successfully extended novel adjectives from the target to the matching test object whether these objects were drawn from the same, or different, basic level categories. In contrast, 3-year-olds' extensions were more restricted. They successfully extended novel adjectives if the target and test objects were drawn from the same basic level category but failed to do so if the objects were drawn from different basic level categories (Experiment 1). However, if 3-year-olds (n = 20) were first permitted to extend a novel adjective to objects within the same basic level category, they were subsequently able to extend that novel adjective broadly to objects from different basic level categories (Experiment 2). Thus, basic level object categories serve as an initial foundation in the process of mapping novel adjectives to object properties.

Child Language↗
PubMed2000

Structure and mutation analysis of the gene encoding DNA fragmentation factor 40 (caspase-activated nuclease), a candidate neuroblastoma tumour suppressor gene.

We have characterised the DFFB gene, encoding the active subunit of the apoptotic nuclease DNA fragmentation factor (DFF40). DFFB maps to 1p36, near the imprinted putative tumour suppressor gene TP73. The DFFA gene (encoding the inhibitory DFF45 subunit) also maps to 1p36.2-36.3, and we show by FISH that DFFB lies distal to DFFA. We have also mapped a processed DFFB pseudogene to chromosome 9. DFFB itself has seven coding exons spanning 10 kb. Exhaustive mutation screening of 41 neuroblastomas and other tumours in which a 1p36 tumour suppressor gene is implicated showed no tumour-specific mutations. A coding region polymorphism was used to demonstrate uniformly biallelic expression in human fetal DFFB transcripts. Since the putative neuroblastoma tumour suppressor gene in distal 1p36 is predicted to be maternally expressed, the lack of imprinting and absence of somatic mutations in DFFB indicate that it is probably not the neuroblastoma tumour suppressor gene.

Apoptosis↗
PubMed2001

The AZFc region of the Y chromosome features massive palindromes and uniform recurrent deletions in infertile men.

Deletions of the AZFc (azoospermia factor c) region of the Y chromosome are the most common known cause of spermatogenic failure. We determined the complete nucleotide sequence of AZFc by identifying and distinguishing between near-identical amplicons (massive repeat units) using an iterative mapping-sequencing process. A complex of three palindromes, the largest spanning 3 Mb with 99.97% identity between its arms, encompasses the AZFc region. The palindromes are constructed from six distinct families of amplicons, with unit lengths of 115-678 kb, and may have resulted from tandem duplication and inversion during primate evolution. The palindromic complex contains 11 families of transcription units, all expressed in testis. Deletions of AZFc that cause infertility are remarkably uniform, spanning a 3.5-Mb segment and bounded by 229-kb direct repeats that probably served as substrates for homologous recombination.

Base Sequence↗
PubMed1993

The locomotion, shape and pseudopodial dynamics of unstimulated Dictyostelium cells are not random.

The dynamic periphery of unstimulated, preaggregation, hunger-stage Dictyostelium discoideum amoebae was investigated by time-lapse videomicroscopy and digital image processing. Circular maps (i.e. of each of 360 radii around the cell transformed upon Cartesian coordinates) were constructed around the centroid of individual cell images and analysed in time series. This novel technique generated spatiotemporal structures of various degrees of order in the maps, which resemble classical wave interference patterns. The patterns thus demonstrate that cell movement is not random and that cells are intrinsically vibrating bodies, transited by self-organized, superpositioned, harmonic modes of rotating oscillatory waves (ROWS). These waves appear to depend upon spatiotemporal oscillations in the physicochemical reactions associated with actin polymerization, and they govern pseudopodial movements, cell shape and locomotion generally. ROWS in this case are unrelated to the cyclic-AMP-regulated oscillations, which characterize later, aggregative populations of Dictyostelium. However, the exposure of aggregation-stage cells to a pulse of the chemoattractant cyclic-AMP induces a characteristic sequence of changes in the global cellular concentration and spatiotemporal distribution of fibrillar (F-)actin. This reaction begins with what appears to be a phase resetting of ROWS and it may, therefore, underlie the cellular perception of and response to chemotactic signals. We also develop here an analytical mathematical description of ROWS, and use it to simulate cell movements accurately.

Actins↗
PubMed1996

Differential temporal evolution of post-training changes in regional brain glucose metabolism induced by repeated spatial discrimination training in mice: visualization of the memory consolidation process?

The present study analyses the effects of the stage of learning on the spatial patterns and time-course of [14C]glucose uptake in BALB/c mice brain regions produced by spatial discrimination training in an eight-arm radial maze. Our particular approach was designed to follow, during the post-training period, the level of functional activity in individual brain areas which may underlie the memory consolidation process. Regional mapping of relative [14C]glucose uptake was assessed at three post-training time intervals (5 min, 1 and 3 h) after either the first (Day 1), the fourth (Day 4) or the last (Day 9) daily training session of the discrimination task and compared with sham-conditioned animals placed in the same experimental environment. The results indicated that numerous subcortical and cortical brain regions exhibit metabolic alterations following the acquisition of the spatial discrimination task. These alterations, which were specifically related to learning since they did not appear in sham-conditioned animals, were functions both of the post-training interval studied and of the degree of mastery of the task. On Day 1, a progressive, time-dependent and sequential increase in labelling was found from subcortical (5 min post-training) to cortical regions (3 h post-training). On Day 4, a peak of cortical metabolic activation was identified at 1 h post-training. In contrast, on Day 9, maximum labelling was found 5 min post-training in all subcortical and cortical regions followed by a general monotonic decline at 1 and 3 h post-training. These findings, which show widely distributed changes of metabolic activity in the brain, are consistent with the hypothesis that learning involves distributed neural networks. The sequential activation from subcortical to cortical regions seems to indicate a general mechanism whose function would ultimately be to store cortical memory representations. The acquisition-dependent shifts in the patterns of post-training metabolic labelling observed as a function of task mastery may be taken to represent a visualization of the spatio-temporal evolution of the networks of brain structures actively engaged in the memory consolidation process. In particular, the present data suggest that the duration of post-acquisition memory processing is a function of the quantity of new information which has to be dealt with by the central nervous system.

Animals↗
PubMedDate not supplied

The service blueprint as a tool for designing innovative pharmaceutical services.

OBJECTIVE: To describe service blueprints, discuss their need and design, and provide examples of their use in advancing pharmaceutical care. BACKGROUND: Service blueprints are pictures or maps of service processes that permit the people involved in designing, providing, managing, and using the service to better understand them and deal with them objectively. A service blueprint simultaneously depicts the service process and the roles of consumers, service providers, and supporting services. Service blueprints can be useful in pharmacy because many of the obstacles to pharmaceutical care are a result of insufficient planning by service designers and/or poor communication between those designing services and those implementing them. One consequence of this poor design and communication is that many consumers and third party payers are uninformed about pharmacist roles. Service blueprints can be used by pharmacists to promote the value of pharmaceutical care to consumers and other decision makers. They can also assist in designing better pharmaceutical services. METHODS: Blueprints are designed by identifying and mapping a process from the consumer's point of view, mapping employee actions and support activities, and adding visible evidence of service at each consumer action step. Key components of service blueprints are consumer actions, "onstage" and "backstage" employee actions, and support processes. DISCUSSION: Blueprints can help pharmacy managers identify and correct problems with the service process, provide pharmacy employees an opportunity to offer feedback in the planning stages of services, and demonstrate the value of pharmaceutical services to consumers. CONCLUSION: Service blueprints can be a valuable tool for designing, implementing, and evaluating pharmacy services.

Communication↗
PubMed2000

Is keratoconus a true ectasia? An evaluation of corneal surface area.

BACKGROUND: Keratoconus has long been considered to be an ectasia produced by stromal stretching. Although stretching should result in increased corneal surface area, previous observations of topography during progression of keratoconus have suggested that surface area may actually be conserved. A novel objective surface area measurement based on corneal topography was tested and applied to data from actual corneas under various conditions for comparative analysis. SETTING: The LSU Eye Center clinic videokeratography archives. METHODS: TMS-1 videokeratography files (Tomey Corp, Cambridge, Mass) were obtained from 6 groups of corneas: normal (n = 29), keratoconus from mild to severe states (n = 51), topographically judged keratoconus-suspect conditions (n = 10), postoperative photorefractive keratectomy for myopia (n = 39), with-the-rule corneal astigmatism (n = 17), and keratoglobus (n = 1). Additionally, 3 different spherical test surfaces were analyzed to verify the accuracy of the process. Only maps with no missing data out to ring 29 were used. The cumulative surface area from center to periphery was determined by calculating and summing the area of individual patches along consecutive annular rings. Mean surface area with respect to mean chord radius was plotted for each corneal condition, and curve fitting was used to extend each result to a 5. 85-mm limbus. Means, SEs, and 95% confidence intervals were calculated at intervals for statistical comparisons among all groups. Computer-generated surfaces helped to evaluate the relationship between shape and surface area. RESULTS: When videokeratographic test targets were used, surface area error was less than 2%, which was deemed acceptable. Normal corneas had a mean +/- SE surface area of 120.3 +/- 2.2 mm(2), whereas all keratoconus corneas combined had a mean +/- SE surface area of 116.2 +/- 3.4 mm(2). The difference was not significant at any chord radius (analysis of variance, P<. 05). The keratoglobus cornea was found to have a surface area of 129. 9 mm(2), which was 7.98% greater than normal. An individual with progressive keratoconus exhibited no appreciable trend toward increasing surface area during a 76-month period. The corneas in the other groups resembled normal corneas in their total surface area. CONCLUSIONS: With the exception of the single case of keratoglobus, corneal surface area tended to be conserved near a value of 120 mm(2) for all groups in the study, including corneas with keratoconus. Surface area is remarkably insensitive to curvature change near the vertex. Flattening seen in the periphery of corneas with keratoconus suggests that biomechanical coupling compensates for any increase in curvature occurring in the region of the cone itself. Thus, it seems that keratoconus is not a true ectasia as is keratoglobus, but rather a specialized type of warpage, at least in mild to moderate forms of the disease. Arch Ophthalmol. 2000;118:1179-1186

Algorithms↗