clusterBMA: Bayesian model averaging for clustering

Various methods have been developed to combine inference across multiple sets of results for unsupervised clustering, within the ensemble clustering literature. The approach of reporting results from one `best' model out of several candidate clustering models generally ignores the uncertainty that arises from model selection, and results in inferences that are sensitive to the particular model and parameters chosen. Bayesian model averaging (BMA) is a popular approach for combining results across multiple models that offers some attractive benefits in this setting, including probabilistic interpretation of the combined cluster structure and quantification of model-based uncertainty. In this work we introduce clusterBMA, a method that enables weighted model averaging across results from multiple unsupervised clustering algorithms. We use clustering internal validation criteria to develop an approximation of the posterior model probability, used for weighting the results from each model. From a consensus matrix representing a weighted average of the clustering solutions across models, we apply symmetric simplex matrix factorisation to calculate final probabilistic cluster allocations. In addition to outperforming other ensemble clustering methods on simulated data, clusterBMA offers unique features including probabilistic allocation to averaged clusters, combining allocation probabilities from 'hard' and 'soft' clustering algorithms, and measuring model-based uncertainty in averaged cluster allocation. This method is implemented in an accompanying R package of the same name

A multi-stage genome-wide association study of bladder cancer identifies multiple susceptibility loci.

We conducted a multi-stage, genome-wide association study of bladder cancer with a primary scan of 591,637 SNPs in 3,532 affected individuals (cases) and 5,120 controls of European descent from five studies followed by a replication strategy, which included 8,382 cases and 48,275 controls from 16 studies. In a combined analysis, we identified three new regions associated with bladder cancer on chromosomes 22q13.1, 19q12 and 2q37.1: rs1014971, (P = 8 × 10⁻¹²) maps to a non-genic region of chromosome 22q13.1, rs8102137 (P = 2 × 10⁻¹¹) on 19q12 maps to CCNE1 and rs11892031 (P = 1 × 10⁻⁷) maps to the UGT1A cluster on 2q37.1. We confirmed four previously identified genome-wide associations on chromosomes 3q28, 4p16.3, 8q24.21 and 8q24.3, validated previous candidate associations for the GSTM1 deletion (P = 4 × 10⁻¹¹) and a tag SNP for NAT2 acetylation status (P = 4 × 10⁻¹¹), and found interactions with smoking in both regions. Our findings on common variants associated with bladder cancer risk should provide new insights into the mechanisms of carcinogenesis

A multi-stage genome-wide association study of bladder cancer identifies multiple susceptibility loci.

We conducted a multi-stage, genome-wide association study of bladder cancer with a primary scan of 591,637 SNPs in 3,532 affected individuals (cases) and 5,120 controls of European descent from five studies followed by a replication strategy, which included 8,382 cases and 48,275 controls from 16 studies. In a combined analysis, we identified three new regions associated with bladder cancer on chromosomes 22q13.1, 19q12 and 2q37.1: rs1014971, (P = 8 × 10⁻¹²) maps to a non-genic region of chromosome 22q13.1, rs8102137 (P = 2 × 10⁻¹¹) on 19q12 maps to CCNE1 and rs11892031 (P = 1 × 10⁻⁷) maps to the UGT1A cluster on 2q37.1. We confirmed four previously identified genome-wide associations on chromosomes 3q28, 4p16.3, 8q24.21 and 8q24.3, validated previous candidate associations for the GSTM1 deletion (P = 4 × 10⁻¹¹) and a tag SNP for NAT2 acetylation status (P = 4 × 10⁻¹¹), and found interactions with smoking in both regions. Our findings on common variants associated with bladder cancer risk should provide new insights into the mechanisms of carcinogenesis

Identification of a novel susceptibility locus at 13q34 and refinement of the 20p12.2 region as a multi-signal locus associated with bladder cancer risk in individuals of european ancestry

Candidate gene and genome-wide association studies (GWAS) have identified 15 independent genomic regions associated with bladder cancer risk. In search for additional susceptibility variants, we followed up on four promising single-nucleotide polymorphisms (SNPs) that had not achieved genome-wide significance in 6911 cases and 11 814 controls (rs6104690, rs4510656, rs5003154 and rs4907479, P < 1 7 10(-6)), using additional data from existing GWAS datasets and targeted genotyping for studies that did not have GWAS data. In a combined analysis, which included data on up to 15 058 cases and 286 270 controls, two SNPs achieved genome-wide statistical significance: rs6104690 in a gene desert at 20p12.2 (P = 2.19 7 10(-11)) and rs4907479 within the MCF2L gene at 13q34 (P = 3.3 7 10(-10)). Imputation and fine-mapping analyses were performed in these two regions for a subset of 5551 bladder cancer cases and 10 242 controls. Analyses at the 13q34 region suggest a single signal marked by rs4907479. In contrast, we detected two signals in the 20p12.2 region-the first signal is marked by rs6104690, and the second signal is marked by two moderately correlated SNPs (r(2) = 0.53), rs6108803 and the previously reported rs62185668. The second 20p12.2 signal is more strongly associated with the risk of muscle-invasive (T2-T4 stage) compared with non-muscle-invasive (Ta, T1 stage) bladder cancer (case-case P 64 0.02 for both rs62185668 and rs6108803). Functional analyses are needed to explore the biological mechanisms underlying these novel genetic associations with risk for bladder cancer

Kinetics of charge transfer processes in organic solar cells: Implications for the design of acceptor molecules

We report the electronic properties of a new class of non-fullerene electron acceptor molecules with electron affinities tunable over an approximately 1 eV range. This tunability allows us to vary the thermodynamic driving force for electron transfer (Delta G degrees) such that it is equal-and-opposite-to the reorganization energy for the ionized states (lambda). We utilize this design principle, derived from Marcus-Hush theory, to optimize the rate of charge transfer in blends of these acceptors with poly(3-n-hexylthiophene-2,5-diyl) (P3HT) - a standard organic solar cell donor material. We show that computationally inexpensive calculations can be used to parameterize Marcus-Hush theory so as to correctly predict whether quenching will occur. Arguments based solely on energetics are common in the literature and we show that such theories do not predict the trends observed in our photoluminescence quenching experiments. This is the case whether the energies determined from experiments [cyclic voltammetry (CV) and the optical gap) or calculated from density functional theory for the solid state. We predict essentially barrier-less photoelectron transfer (PET) from P3HT to the acceptor 2-[{7-(9,9-di-n-propyl-9H-fluoren-2-yl)benzo[c] [1,2,5] thiadiazol-4-yl}methylene]malononitrile (or K12), consistent with the experimental photoluminescence quenching efficiencies found for P3HT:K12 blends. Our results clearly show that energetics alone is not sufficient to predict PET between the acceptor-donor pair, and that kinetics are an important determining factor. (C) 2012 Elsevier B.V. All rights reserved

Morphology dependent electron transport in an n-type electron accepting small molecule for solar cell applications

We report on the charge transport properties of a simple solution processable small-molecule electron acceptor, 2-[{7-(9,9-di-n-propyl-9H-fluoren-2-yl)benzo[c][1,2,5]thiadiazol-4-yl}methylene] malononitrile (K12), designed for use in bulk-heterojunction organic photovoltaic cells. It was found that the molecular order in as-cast films can be dramatically improved by annealing at moderate temperatures (60 degrees C), which leads to a greatly enhanced electron mobility. Using the photoinduced charge extraction in linearly increasing voltage technique we measured bulk electron mobilities to be as high as 10(-4) cm(2) V-1 s(-1), comparable with some of the best nonfullerene acceptor materials reported to date. (C) 2011 American Institute of Physics. [doi: 10.1063/1.3556280

A solution processable fluorene-benzothiadiazole small molecule for n-type organic field-effect transistors

We report an n-type organic semiconductor [2-({7-(9,9-di-n-propyl-9H-fluoren-2-yl}benzo[c][1,2,5] thiadiazol-4-yl) methylene]malononitrile (herein referred to as K12) for use in organic field-effect transistors (OFETs). K12 can be processed by spin-coating from solution or by vacuum deposition, organizing into highly orientated microcrystalline structures at modest (75 degrees C) annealing temperatures. OFETs with n-octyltrichlorosilane or hexamethyldisilazane monolayers, or poly(propylene-co-1-butene) (PPCB) modified dielectric surfaces were prepared. The mobility, ON/OFF ratio, threshold voltage, and current hysteresis were found to be dependent on the thermal history of the film and surface onto which it was deposited. The highest OFET mobility achieved was 2.4 X 10(-3) cm(2)/V s, for spin-coated films with a PPCB modified silicon dioxide dielectric. (C) 2011 American Institute of Physics. [doi:10.1063/1.3569818

Identifying the optimum composition in organic solar cells comprising non-fullerene electron acceptors

We explore the inter-relationship between the phase behavior and photovoltaic performance for two blend systems comprising poly(3-n-hexylthiophene-2,5-diyl) (P3HT) as the electron donating moiety and two newly developed small molecule non-fullerene electron acceptors. Binary non-equilibrium temperature/composition phase diagrams of the two systems are prepared from differential scanning calorimetry (DSC) thermograms of blends of different compositions. The phase behavior is correlated with the optoelectronic performance of corresponding binaries in bulk heterojunction (BHJ) solar cells. The thermal and optoelectronic blend characterization is supported with optical microscopy and specular X-ray diffraction (sXRD) experiments. For both electron-accepting compounds the composition yielding the maximum photocurrent generation in devices was found to be in the hypoeutectic regime, i.e. at compositions that are shifted from the eutectic towards the small molecule rich region in the phase diagrams. We demonstrate that measuring the thermal properties of the blends is useful for rapid component ratio optimization and the evaluation of unexplored materials combinations

A flexible n-type organic semiconductor for optoelectronics

n-Type organic semiconductors are important for a range of optoelectronic applications including organic photovoltaic devices, light-emitting diodes, and field effect transistors (FETs). In spite of this clear motivation there has been significantly less development of n-type compounds relative to p-type systems. We have developed a simple, small molecule n-type material, 2-[(7-{9,9-di-n-propyl-9H-fluoren-2-yl}benzo[c][1,2,5]thiadiazol-4-yl)methylene]malononitrile (K12), that can be processed either by spin-coating from solution or evaporation in vacuum. The thermal properties of K12 enable the film morphology to be controlled at easily accessible temperatures allowing the charge mobility to be tuned over two orders of magnitude. The electron mobility in the films was found to be independent of the initial processing conditions (solution or evaporation). The electron mobility measured in a FET configuration was of the order of 10(-3) cm(2) V-1 s(-1) for films prepared via either processing method whilst Photoinduced Charge Extraction in Linearly Increasing Voltage (PhotoCELIV) gave a mobility of order 10(-4) cm(2) V-1 s(-1)