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Biomedical subjects

B R Holland

Publications and source records attributed to B R Holland.

12 recordsLinked to original sources
PubMed2005

Selecting representative model micro-organisms.

BACKGROUND: Micro-biological research relies on the use of model organisms that act as representatives of their species or subspecies, these are frequently well-characterized laboratory strains. However, it has often become apparent that the model strain initially chosen does not represent important features of the species. For micro-organisms, the diversity of their genomes is such that even the best possible choice of initial strain for sequencing may not assure that the genome obtained adequately represents the species. To acquire information about a species' genome as efficiently as possible, we require a method to choose strains for analysis on the basis of how well they represent the species. RESULTS: We develop the Best Total Coverage (BTC) method for selecting one or more representative model organisms from a group of interest, given that rough genetic distances between the members of the group are known. Software implementing a "greedy" version of the method can be used with large data sets, its effectiveness is tested using both constructed and biological data sets. CONCLUSION: In both the simulated and biological examples the greedy-BTC method outperformed random selection of model organisms, and for two biological examples it outperformed selection of model strains based on phylogenetic structure. Although the method was designed with microbial species in mind, and is tested here on three microbial data sets, it will also be applicable to other types of organism.

Bacteria↗
PubMed2004

The MinMax Squeeze: guaranteeing a minimal tree for population data.

We report that for population data, where sequences are very similar to one another, it is often possible to use a two-pronged (MinMax Squeeze) approach to prove that a tree is the shortest possible under the parsimony criterion. Such population data can be in a range where parsimony is a maximum likelihood estimator. This is in sharp contrast to the case with species data, where sequences are much further apart and the problem of guaranteeing an optimal phylogenetic tree is known to be computationally prohibitive for realistic numbers of species, irrespective of whether likelihood or parsimony is the optimality criterion. The Squeeze uses both an upper bound (the length of the shortest tree known) and a lower bound derived from partitions of the columns (the length of the shortest tree possible). If the two bounds meet, the shortest known tree is thus proven to be a shortest possible tree. The implementation is first tested on simulated data sets and then applied to 53 complete human mitochondrial genomes. The shortest possible trees for those data have several significant improvements from the published tree. Namely, a pair of Australian lineages comes deeper in the tree (in agreement with archaeological data), and the non-African part of the tree shows greater agreement with the geographical distribution of lineages.

Computational Biology↗
PubMed2003

Outgroup misplacement and phylogenetic inaccuracy under a molecular clock--a simulation study.

We conducted a simulation study of the phylogenetic methods UPGMA, neighbor joining, maximum parsimony, and maximum likelihood for a five-taxon tree under a molecular clock. The parameter space included a small region where maximum parsimony is inconsistent, so we tested inconsistency correction for parsimony and distance correction for neighbor joining. As expected, corrected parsimony was consistent. For these data, maximum likelihood with the clock assumption outperformed each of the other methods tested. The distance-based methods performed marginally better than did maximum parsimony and maximum likelihood without the clock assumption. Data correction was generally detrimental to accuracy, especially for short sequence lengths. We identified another region of the parameter space where, although consistent for a given method, some incorrect trees were each selected with up to twice the frequency of the correct (generating) tree for sequences of bounded length. These incorrect trees are those where the outgroup has been incorrectly placed. In addition to this problem, the placement of the outgroup sequence can have a confounding effect on the ingroup tree, whereby the ingroup is correct when using the ingroup sequences alone, but with the inclusion of the outgroup the ingroup tree becomes incorrect.

Cluster Analysis↗
PubMed2002

Delta plots: a tool for analyzing phylogenetic distance data.

A method is described that allows the assessment of treelikeness of phylogenetic distance data before tree estimation. This method is related to statistical geometry as introduced by Eigen, Winkler-Oswatitsch, and Dress (1988 [Proc. Natl. Acad. Sci. USA. 85:5913-5917]), and in essence, displays a measure for treelikeness of quartets in terms of a histogram that we call a delta plot. This allows identification of nontreelike data and analysis of noisy data sets arising from processes such as, for example, parallel evolution, recombination, or lateral gene transfer. In addition to an overall assessment of treelikeness, individual taxa can be ranked by reference to the treelikeness of the quartets to which they belong. Removal of taxa on the basis of this ranking results in an increase in accuracy of tree estimation. Recombinant data sets are simulated, and the method is shown to be capable of identifying single recombinant taxa on the basis of distance information alone, provided the parents of the recombinant sequence are sufficiently divergent and the mixture of tree histories is not strongly skewed toward a single tree. delta Plots and taxon rankings are applied to three biological data sets using distances derived from sequence alignment, gene order, and fragment length polymorphism.

Models, Genetic↗
PubMed2000

Multiple maxima of likelihood in phylogenetic trees: an analytic approach.

Maximum likelihood (ML) is a widely used criterion for selecting optimal evolutionary trees. However, the nature of the likelihood surface for trees is still not sufficiently understood, especially with regard to the frequency of multiple optima. Here, we initiate an analytic study for identifying sequences that generate multiple optima. We concentrate on the problem of optimizing edge weights for a given tree or trees (as opposed to searching through the space of all trees). We report a new approach to computing ML directly, which we have used to find large families of sequences that have multiple optima, including sequences with a continuum of optimal points. Such data sets are best supported by different (two or more) phylogenies that vary significantly in their timings of evolutionary events. Some standard biological processes can lead to data with multiple optima, and consequently the field needs further investigation. Our results imply that hill-climbing techniques as currently implemented in various software packages cannot guarantee that one will find the global ML point, even if it is unique.

Evolution, Molecular↗
PubMed1997

[Comparison of ventilation-/perfusion scintigraphy with spiral CT in acute lung embolism].

AIM: Evaluation of the validity of spiral-CT compared with ventilation/perfusion (v/p) scintigraphy, the standard diagnostic tool in patients with suspected pulmonary embolism. PATIENTS AND METHODS: Prospective study of 70 patients with symptoms of acute pulmonary embolism: examination with both methods within 4 hours. RESULTS: In 46 patients pulmonary embolism could be unequivocally excluded by both methods. Patients with high-probability-Tc-scans predominantly had central emboli on CT. In cases with medium or low probability-Tc-scans thrombi were usually visible in segmental arteries. In one patient with a non-suspicious scintigram spiral-CT was able to detect emboli in multiple segmental arteries. CONCLUSION: Spiral-CT is a fast, safe and almost always available method for detection of pulmonary embolism. In our hands it is superior to v/p-scintigraphy. It allows direct detection of a thrombus and has additional advantages in differential diagnosis (e. g. lung carcinoma, infectious infiltration). In patients with clinical suspicion of pulmonary embolism spiral-CT should be the primary diagnostic modality.

Aged↗
PubMed1996

[Spiral computerized tomography of acute abdominal aortic aneurysm with optimal 3-D image reconstruction].

43 of 46 consecutive patients with suspected rupture of abdominal aortic aneurysm could be examined by spiral CT. Rupture of an abdominal vessel was found in 18 patients and proved by surgery. Size and extent of the aneurysm, rupture, dissection and vascular occlusion were demonstrated quickly and precisely by spiral CT, planning of surgical intervention could be optimized. Using spiral CT unnecessary explorative laparotomies could be avoided in 25 patients. In addition spiral CT offers the possibility of multiplanar reconstruction images with spatial visualisation of the vascular system. In 8 patients DSA offered no advantage in comparison with 3-D reconstruction images. Spiral CT meets all requirements for quick and reliable diagnosis in suspected rupture of abdominal vessels. Other imaging modalities like digital subtraction angiography are not necessary for evaluation of abdominal aortic aneurysms.

Aged↗
PubMed1995

[Experimental studies of the visualization of the vertebral body spongiosa by high-resolution computed tomography].

AIM: To show the accuracy and the lower limit of visualisation of cancellous bone in high-resolution computed tomography (HR-CT). METHODS: 18 native human lumbar vertebrae were placed in a water phantom and examined by HR-CT. The scans were compared with contact radiographs of correlating thin bone sections by morphologic criteria. RESULTS AND CONCLUSION: The measured lower limit of visualisation of cancellous bone structures is clearly worse than expected from the measurements of spatial resolution with standard phantoms used for HR-CT (0.6 versus 0.4 mm). True and exact imaging of normal cancellous bone cannot be achieved even by modern HR-CT. Noise creates structures mimicking cancellous bone.

Adult↗
PubMed1994

[MRI diagnosis of bone tumors].

Diagnosis of bone tumours is still based on plain films and, if necessary, computed tomography because crucial morphologic criteria such as ossification of tumour matrix, patterns of bone destruction and formation of new bone are not clearly visualized by MRI. Only in a few cases is MRI helpful for characterization of bone lesions. Although MRI is of limited value for differential diagnosis of bone tumours, it may be very helpful for planning of biopsy or surgery by virtue of its ability to demonstrate tumour extent and soft tissue changes. For local staging and follow-up of primary bone tumours MRI is clearly the method of choice. MRI strategy should be coordinated with clinical requirements in order to ensure optimum evaluation of tumour extent, effectiveness of chemotherapy and detection of local recurrence.

Bone Neoplasms↗
PubMed1988

[Magnetic resonance tomographic results in bone changes associated with sclerosis].

We have compared the value of MRI with conventional radiography and CT in 40 predominantly sclerotic skeletal lesions. We have found that sclerosis and other changes in the bone structure can be demonstrated by MRI in much the same way as with conventional radiography and CT. Using high resolution surface coils, it is possible to demonstrate small areas of new bone formation such as periosteal new bone or the calcification within the nidus of an osteoid osteoma. MRI is particularly appropriate if it is necessary to show soft tissue changes within an area of sclerosis, which may be responsible for the new bone formation and which may be masked on radiographs and CT by the surrounding sclerosis.

Bone Diseases↗
PubMedDate not supplied

[Calcifying tendinitis of the femur--diagnosis and differential diagnosis exemplified by 5 cases].

Five cases of calcifying tendinitis of the femur are presented. Diagnosis were proved histologically or catamnestically. The calcifying tendinitis occurred secondary to localized regressive changes in 3 patients; in 2 cases systemic inflammatory disease had to be assumed. In patients with unclear femoral pain and radiologically visible calcifications, especially at the linea aspera, one should include a calcifying tendinitis in the differential diagnosis besides juxtacortical osteosarcoma and myositis ossificans. This entity can sometimes be a symptom of systemic disease such as psoriasis and palmoplantar pustulosis.

Adult↗