Comparison of statistical methods for classification of ovarian cancer using mass spectrometry data

MOTIVATION: Novel methods, both molecular and statistical, are urgently needed to take advantage of recent advances in biotechnology and the human genome project for disease diagnosis and prognosis. Mass spectrometry (MS) holds great promise for biomarker identification and genome-wide protein profiling. It has been demonstrated in the literature that biomarkers can be identified to distinguish normal individuals from cancer patients using MS data. Such progress is especially exciting for the detection of early-stage ovarian cancer patients. Although various statistical methods have been utilized to identify biomarkers from MS data, there has been no systematic comparison among these approaches in their relative ability to analyze MS data. RESULTS: We compare the performance of several classes of statistical methods for the classification of cancer based on MS spectra. These methods include: linear discriminant analysis, quadratic discriminant analysis, k-nearest neighbor classifier, bagging and boosting classification trees, support vector machine, and random forest (RF). The methods are applied to ovarian cancer and control serum samples from the National Ovarian Cancer Early Detection Program clinic at Northwestern University Hospital. We found that RF outperforms other methods in the analysis of MS data.     

A set of simple-sequence repeat (SSR) markers covering the Prunus genome

A set of 109 microsatellite primer pairs recently developed for peach and cherry have been studied in the almond x peach F(2) progeny previously used to construct a saturated Prunus map containing mainly restriction fragment length polymorphism markers. All but one gave amplification products, and 87 (80%) segregated in the progeny and detected 96 loci. The resulting Prunus map contains a total of 342 markers covering a total distance of 522 cM. The approximate position of nine additional simple sequence repeats (SSRs) was established by comparison with other almond and peach maps. SSRs were placed in all the eight linkage groups of this map, and their distribution was relatively even, providing a genome-wide coverage with an average density of 5.4 cM/SSR. Twenty-four single-locus SSRs, highly polymorphic in peach, and each falling within 24 evenly spaced approximately 25-cM regions covering the whole Prunus genome, are proposed as a 'genotyping set' useful as a reference for fingerprinting, pedigree and genetic analysis of this species.     

Expressed sequence tag profiling identifies developmental and anatomic partitioning of gene expression in the mouse prostate

Background  

The prostate gland is an organ with highly specialized functional attributes that serves to enhance the fertility of mammalian species. Much of the information pertaining to normal and pathological conditions affecting the prostate has been obtained through extensive developmental, biochemical and genetic analyses of rodent species. Although important insights can be obtained through detailed anatomical and histological assessments of mouse and rat models, further mechanistic explanations are greatly aided through studies of gene and protein expression.     

Reproduction in captive common marmosets (Callithrix jacchus)

Though sexual maturation may begin at around one year of age, first successful reproduction of the common marmoset (Callithrix jacchus) is likely to be later, and it is generally recommended that animals not be mated before 1.5 years of age. The average gestation period is estimated to be 143 to 144 days. A crown-rump length measurement taken by use of ultrasonography during the linear, rapid, prenatal growth phase (between approx. days 60 and 95) can be compared against standard growth curves to estimate delivery date to within 3 to 4 days, on average. Marmosets produce more young per delivery than does any other anthropoid primate, and have more variation in litter size. Many long-established colonies report that triplets are the most common litter size, and there is documented association between higher maternal body weight and higher ovulation numbers. Higher litter sizes generally do not generate higher numbers of viable young. Marmosets are unusual among primates in having a postpartum ovulation that typically results in conception and successful delivery; reported median inter-birth intervals range from 154 to 162 days. However, pregnancy losses are quite common; one study of a large breeding colony indicated 50 percent loss between conception and term delivery. The average life span for breeding females is around six years; the range of reported average lifetime number of litters for a breeding pair is 3.45 to 4.0. Our purpose is to provide an overview of reproduction in the common marmoset, including basic reproductive life history, lactation and weaning, social housing requirements, and common problems encountered in the captive breeding of this species. A brief comparison between marmoset and tamarin reproduction also will be provided.     

An analysis of two refolding routes for a C-terminally truncated human collagenase-3 expressed in Escherichia coli

We describe here the expression of a C-terminally truncated form of human procollagenase-3 in Escherichia coli. The protein was found almost exclusively in inclusion bodies that were solubilized and refolded by two separate methods and then purified on Ni-NTA agarose. The purified proenzyme could be activated with either trypsin or APMA and active enzyme could be purified on a peptidic hydroxamate affinity column. Competitive elution from the affinity matrix yielded a highly purified preparation.     

Improved growth of cultured brain microvascular endothelial cells on glass coated with a biological matrix

An improved method for culturing primary rat brain capillary endothelial cells on glass has been developed, using a corneal extracellular matrix coat. Since the collagen-coated plastic attachment surface conventionally used for primary cultures of brain microvascular endothelium gives a high level of background fluorescence in microfluorimetric studies, an alternative attachment surface was tested involving no plastic element. Five substrata combinations were examined and a new combination of glass and corneal endothelial extracellular matrix coat was found to provide excellent cell adhesion, culture growth and purity. Other established substrata combinations tested for comparison, either involved plastic, or used glass with collagen or carbodiimide and collagen coating but the last two gave poor endothelial cell adhesion and growth. Our method using this new attachment surface combination results in stable and pure endothelial cultures, as verified by immunocytochemistry, which are suitable for fluorimetric investigations.     

Correlates of Recent Declines of Rodents in Northern and Southern Australia: Habitat Structure Is Critical

Australia has experienced dramatic declines and extinctions of its native rodent species over the last 200 years, particularly in southern Australia. In the tropical savanna of northern Australia significant declines have occurred only in recent decades. The later onset of these declines suggests that the causes may differ from earlier declines in the south. We examine potential regional effects (northern versus southern Australia) on biological and ecological correlates of range decline in Australian rodents. We demonstrate that rodent declines have been greater in the south than in the tropical north, are strongly influenced by phylogeny, and are consistently greater for species inhabiting relatively open or sparsely vegetated habitat. Unlike in marsupials, where some species have much larger body size than rodents, body mass was not an important predictor of decline in rodents. All Australian rodent species are within the prey-size range of cats (throughout the continent) and red foxes (in the south). Contrary to the hypothesis that mammal declines are related directly to ecosystem productivity (annual rainfall), our results are consistent with the hypothesis that disturbances such as fire and grazing, which occur in non-rainforest habitats and remove cover used by rodents for shelter, nesting and foraging, increase predation risk. We agree with calls to introduce conservation management that limits the size and intensity of fires, increases fire patchiness and reduces grazing impacts at ecological scales appropriate for rodents. Controlling feral predators, even creating predator-free reserves in relatively sparsely-vegetated habitats, is urgently required to ensure the survival of rodent species, particularly in northern Australia where declines are not yet as severe as those in the south.