Classification and Categorical Inputs with Treed Gaussian Process Models

Recognizing the successes of treed Gaussian process (TGP) models as an interpretable and thrifty model for nonparametric regression, we seek to extend the model to classification. Both treed models and Gaussian processes (GPs) have, separately, enjoyed great success in application to classification problems. An example of the former is Bayesian CART. In the latter, real-valued GP output may be utilized for classification via latent variables, which provide classification rules by means of a softmax function. We formulate a Bayesian model averaging scheme to combine these two models and describe a Monte Carlo method for sampling from the full posterior distribution with joint proposals for the tree topology and the GP parameters corresponding to latent variables at the leaves. We concentrate on efficient sampling of the latent variables, which is important to obtain good mixing in the expanded parameter space. The tree structure is particularly helpful for this task and also for developing an efficient scheme for handling categorical predictors, which commonly arise in classification problems. Our proposed classification TGP (CTGP) methodology is illustrated on a collection of synthetic and real data sets. We assess performance relative to existing methods and thereby show how CTGP is highly flexible, offers tractable inference, produces rules that are easy to interpret, and performs well out of sample.     

Sequence of Plasmodium falciparum chromosomes 2, 10, 11 and 14

The mosquito-borne malaria parasite Plasmodium falciparum kills an estimated 0.7-2.7 million people every year, primarily children in sub-Saharan Africa. Without effective interventions, a variety of factors-including the spread of parasites resistant to antimalarial drugs and the increasing insecticide resistance of mosquitoes-may cause the number of malaria cases to double over the next two decades. To stimulate basic research and facilitate the development of new drugs and vaccines, the genome of Plasmodium falciparum clone 3D7 has been sequenced using a chromosome-by-chromosome shotgun strategy. We report here the nucleotide sequences of chromosomes 10, 11 and 14, and a re-analysis of the chromosome 2 sequence. These chromosomes represent about 35% of the 23-megabase P. falciparum genome.     

Low-penetrance susceptibility to breast cancer due to CHEK2(*)1100delC in noncarriers of BRCA1 or BRCA2 mutations

Mutations in BRCA1 and BRCA2 confer a high risk of breast and ovarian cancer, but account for only a small fraction of breast cancer susceptibility. To find additional genes conferring susceptibility to breast cancer, we analyzed CHEK2 (also known as CHK2), which encodes a cell-cycle checkpoint kinase that is implicated in DNA repair processes involving BRCA1 and p53 (refs 3,4,5). We show that CHEK2(*)1100delC, a truncating variant that abrogates the kinase activity, has a frequency of 1.1% in healthy individuals. However, this variant is present in 5.1% of individuals with breast cancer from 718 families that do not carry mutations in BRCA1 or BRCA2 (P = 0.00000003), including 13.5% of individuals from families with male breast cancer (P = 0.00015). We estimate that the CHEK2(*)1100delC variant results in an approximately twofold increase of breast cancer risk in women and a tenfold increase of risk in men. By contrast, the variant confers no increased cancer risk in carriers of BRCA1 or BRCA2 mutations. This suggests that the biological mechanisms underlying the elevated risk of breast cancer in CHEK2 mutation carriers are already subverted in carriers of BRCA1 or BRCA2 mutations, which is consistent with participation of the encoded proteins in the same pathway.     

The reversibility of mitotic exit in vertebrate cells

A guiding hypothesis for cell-cycle regulation asserts that regulated proteolysis constrains the directionality of certain cell-cycle transitions. Here we test this hypothesis for mitotic exit, which is regulated by degradation of the cyclin-dependent kinase 1 (Cdk1) activator, cyclin B. Application of chemical Cdk1 inhibitors to cells in mitosis induces cytokinesis and other normal aspects of mitotic exit, including cyclin B degradation. However, chromatid segregation fails, resulting in entrapment of chromatin in the midbody. If cyclin B degradation is blocked with a proteasome inhibitor or by expression of non-degradable cyclin B, Cdk inhibitors will nonetheless induce mitotic exit and cytokinesis. However, if after mitotic exit, the Cdk1 inhibitor is washed free from cells in which cyclin B degradation is blocked, the cells can revert back to M phase. This reversal is characterized by chromosome recondensation, nuclear envelope breakdown, assembly of microtubules into a mitotic spindle, and in most cases, dissolution of the midbody, reopening of the cleavage furrow, and realignment of chromosomes at the metaphase plate. These findings demonstrate that proteasome-dependent degradation of cyclin B provides directionality for the M phase to G1 transition.     

No supernovae associated with two long-duration gamma-ray bursts

It is now accepted that long-duration gamma-ray bursts (GRBs) are produced during the collapse of a massive star. The standard 'collapsar' model predicts that a broad-lined and luminous type Ic core-collapse supernova accompanies every long-duration GRB. This association has been confirmed in observations of several nearby GRBs. Here we report that GRB 060505 (ref. 10) and GRB 060614 (ref. 11) were not accompanied by supernova emission down to limits hundreds of times fainter than the archetypal supernova SN 1998bw that accompanied GRB 980425, and fainter than any type Ic supernova ever observed. Multi-band observations of the early afterglows, as well as spectroscopy of the host galaxies, exclude the possibility of significant dust obscuration and show that the bursts originated in actively star-forming regions. The absence of a supernova to such deep limits is qualitatively different from all previous nearby long-duration GRBs and suggests a new phenomenological type of massive stellar death.     

Land snail diversity in Wind Cave National Park, South Dakota

Eighty-two soil samples and additional hand-collection in Wind Cave National Park yielded over 2000 terrestrial gastropod specimens. The specimens represent 26 different species, including a South Dakota species of concern, Vertigo arthuri . New South Dakota state records for Gastrocopta pellucida and Vertigo tridentata were recorded. Samples from grassland habitats were less likely to contain snails and had lower species richness than samples from either forest or shrubland habitats. Canyons, creek beds, bases of limestone cliffs, and shrublands are important habitats for snails in the park.     

Breeding and parental care in the endangered Tehuantepec jackrabbit ( Lepus flavigularis )

We documented date and duration of each breeding phase, breeding rate, nursing behavior, parental care, and leveret survival of the Tehuantepec jackrabbit ( Lepus flavigularis ), a critically endangered lagomorph. Between June 2006 and May 2008, we observed 60 adult radio-collared jackrabbits in Oaxaca, México. Tehuantepec jackrabbits exhibit breeding behaviors 250 days out of the year, with a high-intensity period during the rainy season (May–October). Females give birth to 2 leverets 32 days after copulation. Directly after birth, leverets are put into “beds” or “nests,” which are depressions in the ground covered by prairie grass ( Jouvea pilosa ). Females return to nurse and groom the leverets once per day until the leverets are weaned (12 days after birth). The breeding season and parental care behaviors of Tehuantepec jackrabbits are similar to those of other jackrabbits. Females produced an average of 2 litters per breeding season. The breeding rate for the Tehuantepec jackrabbit (4 leverets per breeding female per breeding season) is lower than the average of other species in the genus Lepus. The survival rate of Tehuantepec jackrabbit leverets (50% at day 19) is higher than that of other leporids. Predation by domestic dogs ( Canis familiaris ) is the main cause of mortality. Understanding reproductive behavior is critical for captive breeding, reintro duction, and conservation efforts for endangered leporids such as the Tehuantepec jackrabbit. Documentamos la fecha y la duración de cada fase de la reproducción, la tasa reproductiva, el amamantamiento, el cuidado parental y los instintos de supervivencia de los lebratos de la liebre de Tehuantepec ( Lepus flavigularis ), un lagomorfo en peligro crítico de extinción. Entre junio de 2006 y mayo de 2008 observamos 60 liebres adultas con collares radiotransmisores en Oaxaca, Mexico. Las liebres de Tehuantepec se reproducen 250 días del año, con un período de alta intensidad durante la estación lluviosa (de mayo a octubre). Las hembras paren 2 lebratos 32 días después de la cópula; colocan a los lebratos en “camas”, o huecos en el suelo cubiertos del pasto Jouvea pilosa, justo después de nacer. Las hembras regresan para amamantar y limpiar a los lebratos una vez cada tarde hasta destetarlos 12 días después de nacer. La temporada de reproducción y el cuidado parental de la liebre de Tehuantepec son parecidos a los de otras liebres. En promedio, las hembras producen 2 crías cada temporada de reproducción. La tasa de reproducción de la liebre de Tehuantepec (4 lebratos por hembra reproductora por temporada de reproducción) está por debajo del promedio de otras especies del género Lepus. La tasa de supervivencia de los lebratos de la liebre de Tehuantepec (50% al día 19) es superior a la que se ha documentado para otros lepóridos, siendo la principal causa de mortalidad la depredación por los perros domésticos ( Canis familiaris ). Es crucial entender el comportamiento reproductor para la crianza en cautiverio, la reintroducción y para los esfuerzos de conservación de lepóridos que están en peligro de extinción tal como occure con la liebre de Tehuantepec.     

Unravelling the signal-transduction network in B lymphocytes

The Alliance for Cellular Signaling has chosen the mouse B lymphocyte as a model system to understand basic principles that govern cellular signalling. Progress to that end has focused initially on establishing a reproducible experimental cell system and characterizing essential signalling responses. Although unravelling this complex network will take years, findings revealed in the interim will prove immensely useful to the scientific community at large.