Arief Gusnanto

• University of Leeds

What is the optimal level of questionnaire detail required to measure bilingual language experience? This empirical evaluation compares alternative measures of language exposure of varying cost (i.e., questionnaire detail) in terms of their performance as predictors of oral language outcomes. The alternative measures were derived from Q-BEx questio...

Glioblastoma (GBM), the most aggressive adult brain cancer, comprises a complex tumour microenvironment (TME) with diverse cellular interactions driving progression and pathobiology. How these spatial patterns and interactions evolve with treatment remains unclear. Here, we apply imaging mass cytometry to analyse protein-level changes in paired pre...

Microsatellite instability (MSI) occurs across a number of cancers and is associated with different clinical characteristics when compared to microsatellite stable (MSS) cancers. As MSI cancers have different characteristics, routine MSI testing is now recommended for a number of cancer types including colorectal cancer (CRC). Using gene panels for...

Bilingual children’s language abilities are influenced by the richness of their language experience, which is typically estimated using parental questionnaires and often expressed as a composite score based on frequency-based variables (e.g., time spent reading). We evaluated whether the composite richness score in the Q-BEx questionnaire (De Cat e...

Copy number alterations (CNA) are structural variation in the genome, in which some regions exhibit more or less than the normal two chromosomal copies. This genomic CNA profile provides critical information in tumour progression and is therefore informative for patients' survival. It is currently a statistical challenge to model patients' survival...

Myalgic Encephalomyelitis (ME) /Chronic Fatigue Syndrome (CFS) is a severely debilitating and complex illness of uncertain aetiology, affecting the lives of millions and characterised by prolonged fatigue. The initiating factors and mechanisms leading to chronic debilitating muscle fatigue in ME/CFS are unknown and are complicated by the time requi...

Two-sample tests are probably the most commonly used tests in statistics. These tests generally address one aspect of the samples' distribution, such as mean or variance. When the null hypothesis is that two distributions are equal, the Anderson–Darling (AD) test, which is developed from the Cramer–von Mises (CvM) test, is generally employed. Unfor...

The purpose of this study is to highlight the application of sparse logistic regression models in dealing with prediction of tumour pathological subtypes based on lung cancer patients' genomic information. We consider sparse logistic regression models to deal with the high dimensionality and correlation between genomic regions. In a hierarchical li...

Clustering amino acids is one of the most challenging problems in functional and structural prediction of protein. Previous studies have proposed clusters based on measurements of physical and biochemical characteristics of the amino acids such as volume, area, hydrophilicity, polarity, hydrogen bonding, shape, and charge. These characteristics, al...

Chronic fatigue syndrome (CFS) is a severely debilitating and complex illness of uncertain cause, characterised by prolonged, fatigue triggered by minimal activity. There is evidence that CFS is associated with chronic inflammation. Studies have shown that plasma levels of cytokines are chronically modified in patients with CFS. This study examined...

Purpose In this study we present a fully automatic method to generate multiparameter normal tissue complication probability (NTCP) models and compare its results with a published model of the same patient cohort. Methods and Materials Data were analysed from 345 rectal cancer patients treated with external radiotherapy to predict the risk of patie...

We introduce a new method to test efficiently for cospeciation in tritrophic systems. Our method utilises an analogy with electrical circuit theory to reduce higher order systems into bitrophic data sets that retain the information of the original system. We use a sophisticated permutation scheme that weights interactions between two trophic layers...

Cognitive deficits in frontal lobe-related (executive) functions in Phenylketonuria (PKU) have been well documented. However, despite studies in PKU mice revealing reduced hippocampal synaptic connectivity, and volumetric MRI studies showing hippocampal volume loss in PKU patients, we are not aware of any studies assessing aspects of cognition spec...

Bioinformatics is an important research area for statisticians. This discussion provides some additional topics to the paper, namely on statistical contributions to detect differential expressed genes, for protein structure prediction, and for the analysis of highly correlated features in Glycomics datasets.

Motivation: Studying transcript regulatory patterns in cell differentiation is critical in understanding its complex nature of the formation and function of different cell types. This is done usually by measuring gene expression at different stages of the cell differentiation. However, if the gene expression data available are only from the mature...

The literature exploring the executive function correlates of bilingualism is vast, but to date, few studies have concentrated on children, for whom the bilingual advantage appears even more inconsistent than for adults. We investigate a highly heterogeneous group of children (in terms of bilingual experience and socio-economic status) and identify...

A number of areas related to learning under supervision have not been fully investigated, particularly the possibility of incorporating the method of classification into shape analysis. In this regard, practical ideas conducive to the improvement of form classification are the focus of interest. Our proposal is to employ a hybrid classifier built o...

We focus our analysis on the structural alignment of proteins from the trypsin family. Calculating basic summary statistics on the resulting aligned distance matrices revealed an interesting result. We discovered a set of residues where the distance between these specific residues and every other residue in each structure is highly conserved across...

The role of personalised medicine and target treatment in the clinical management of cancer patients has become increasingly important in recent years. This has made the task of precise histological substratification of cancers crucial. Increasingly genomic data are being seen as a valuable classifier. Specifically, copy number alteration (CNA) pro...

In a calibration of near-infrared (NIR) instrument, we regress some chemical compositions of interest as a function of their NIR spectra. In this process, we have two immediate challenges: first, the number of variables exceeds the number of observations and, second, the multicollinearity between variables are extremely high. To deal with the chall...

Current high throughput sequencing has greatly transformed genome sequence analysis. In the context of very low- coverage sequencing (<0.1X), performing 'binning' or 'windowing' on mapped short sequences ('reads') is critical to extract genomic information of interest for further evaluation, such as copy number alterations analysis. If the window s...

Our main interest in supervised classification of gene expression data is to infer whether the expressions can discriminate biological characteristics of samples. With thousands of gene expressions to consider, a gene selection has been advocated to decrease classification by including only the discriminating genes. We propose to make the gene sele...

Recent genome-wide association studies have reported the discoveries of genetic variants of small to moderate effects. However, most studies of complex diseases face a great challenge because the number of significant variants is less than what is required to explain the disease heritability. A new approach is needed to recognize all potential disc...

Comparison of read depths from next-generation sequencing between cancer and normal cells makes the estimation of copy number alteration (CNA) possible, even at very low coverage. However, estimating CNA from patients' tumour samples poses considerable challenges due to infiltration with normal cells and aneuploid cancer genomes. Here we provide a...

LPS Supplementary Table 1. RNA yield and quality data for all samples and those included in the study.

LPS Supplementary Table 2. cDNA quantity, quality, labeling and amplification data for all samples and those included in the study.

Supplementary Table 3 Ctrl vs LPS in vitro. Full results of the in vitro experiments.

Supplementary Methods. Full methods of the in vitro experiments.

It is widely accepted that atherosclerosis and inflammation are intimately linked. Monocytes play a key role in both of these processes and we hypothesized that activation of inflammatory pathways in monocytes would lead to, among others, proatherogenic changes in the monocyte transcriptome. Such differentially expressed genes in circulating monocy...

Within the healthy population, there is substantial, heritable, and interindividual variability in the platelet response. We explored whether a proportion of this variability could be accounted for by interindividual variation in gene expression. Through a correlative analysis of genome-wide platelet RNA expression data from 37 subjects representin...

The karyotype of human tumors are often aneuploid: besides these numerical deviations, there are often structural rearrangements within individual chromosomes such as amplifications, deletions and translocations. In the resulting genome, profound and complex alterations in the underlying gene network and dosage occur, giving rise to the observed ma...

Hematopoiesis is a carefully controlled process that is regulated by complex networks of transcription factors that are, in part, controlled by signals resulting from ligand binding to cell-surface receptors. To further understand hematopoiesis, we have compared gene expression profiles of human erythroblasts, megakaryocytes, B cells, cytotoxic and...

Haematopoiesis is a carefully controlled process that is regulated by complex networks of transcription factors that are, in part, controlled by signals resulting from ligand binding to cell surface receptors. In order to further understand haematopoiesis, we have compared gene expression profiles of human erythroblasts, megakaryocytes, B-cells, cy...

Introduction: Inflammatory activation of both circulating blood cells as well as vessel wall cells is a hallmark of atherogenesis. Agonists of the Toll-like receptor 4 pathway, present on white blood cells as well as endothelial cells, have been associated with a pro-atherogenic state. Recently, standardized inflammatory challenge models using lipo...

Platelet Glycoprotein VI (GPVI) is the activatory collagen signalling receptor that transmits an outside-in signal via the FcR gamma-chain. In Caucasians two GP6 haplotypes have been identified which encode GPVI isoforms that differ by five amino-acids. The minor haplotype is associated with a modest but statistically significant reduction in GPVI...

The question of what significance threshold is appropriate for genomewide association studies is somewhat unresolved. Previous theoretical suggestions have yet to be validated in practice, whereas permutation testing does not resolve a discrepancy between the genomewide multiplicity of the experiment and the subset of markers actually tested. We us...

Array comparative genomic hybridization (aCGH) provides a genome-wide technique to screen for copy number alteration. The existing segmentation approaches for analyzing aCGH data are based on modeling data as a series of discrete segments with unknown boundaries and unknown heights. Although the biological process of copy number alteration is discr...

The diagnosis of follicular thyroid carcinoma (FTC) in the absence of metastasis can only be established postoperatively. Moreover, high-risk FTCs are often not identifiable at the time of diagnosis. In this study, we aimed to identify transcriptional markers of malignancy and high-risk disease in follicular thyroid tumors. The expression levels of...

Our ability to detect differentially expressed genes in a microarray experiment can be hampered when the number of biological samples of interest is limited. In this situation, we propose the use of information from self-self hybridizations to acuminate our inference of differential expression. A unified modelling strategy is developed to allow bet...

To highlight the development in microarray data analysis for the identification of differentially expressed genes, particularly via control of false discovery rate. The emergence of high-throughput technology such as microarrays raises two fundamental statistical issues: multiplicity and sensitivity. We focus on the biological problem of identifyin...

To identify previously unknown platelet receptors we compared the transcriptomes of in vitro differentiated megakaryocytes (MKs) and erythroblasts (EBs). RNA was obtained from purified, biologically paired MK and EB cultures and compared using cDNA microarrays. Bioinformatical analysis of MK-up-regulated genes identified 151 transcripts encoding tr...

Platelet Glycoprotein VI (GPVI) is a lineage specific collagen signalling receptor that transmits outside-in signalling via the FcR γ-chain. Two GPVI haplotypes have been identified, ‘a’ and ‘b’, that differ by five amino acids. These substitutions have a profound effect on signalling downstream of GPVI and are also associated with variation in the...

Summary Platelets are derived from a polyploid precursor cell, the megakaryocyte (MK). The MK and the precursor of red cells, the erythroblast (EBs) share a common bipotent progenitor and have closely linked differentiation pathways. We hypothesized that the subset of genes that are differentially expressed between MKs and EBs would contain novel,...

Recent developments in the statistical analysis of genome-wide studies are reviewed. Genome-wide analyses are becoming increasingly common in areas such as scans for disease-associated markers and gene expression profiling. The data generated by these studies present new problems for statistical analysis, owing to the large number of hypothesis tes...

The false discovery rate (fdr) is a key tool for statistical assessment of differential expression (DE) in microarray studies. Overall control of the fdr alone, however, is not sufficient to address the problem of genes with small variance, which generally suffer from a disproportionally high rate of false positives. It is desirable to have an fdr-...

Proteomic and genomic technologies provide powerful tools for characterizing the multitude of events that occur in the anucleate platelet. These technologies are beginning to define the complete platelet transcriptome and proteome as well as the protein-protein interactions critical for platelet function. The integration of these results provides t...

Motivation: In microarray data studies most researchers are keenly aware of the potentially high rate of false positives and the need to control it. One key statistical shift is the move away from the well-known P-value to false discovery rate (FDR). Less discussion perhaps has been spent on the sensitivity or the associated false negative rate (FN...

Microarray experiments produce expression measurements for thousands of genes simultaneously, though usually for a small number of RNA samples. The most common problem is the identification of genes that are differentially expressed between different groups of samples or biological conditions. As the number of genes far exceeds the number of RNA sa...

The fjord-region PAH dibenzo[a,l]pyrene (DBP) is considerably more carcinogenic than the bay-region benzo[a]pyrene (BP). This fact can be ascribed to differences in DNA binding efficiency of their ultimate carcinogenic diol epoxide (DEs) intermediates, differences in structural features of the DNA adducts, and differences in DNA adduct recognition...

Completion of the fission yeast genome sequence has opened up possibilities for post-genomic approaches. We have constructed a DNA microarray for genome-wide gene expression analysis in fission yeast. The microarray contains DNA fragments, PCR-amplified from a genomic DNA template, that represent > 99% of the 5000 or so annotated fission yeast gene...

Standard methods for calibration of near-infrared instruments, such as partial least-squares (PLS) and ridge regression (RR), typically use the full set of wavelengths in the model. In this paper we investigate the effect of variable (wavelength) selection for these two methods on the model prediction. For RR the selection is optimized with respect...