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Modern Applied Statistics With S

1. Type 1 diabetes (due to b-cell destruction, usually leading to absolute insulin deficiency) 2. Type 2 diabetes (due to a progressive insulin secretory defect on the background of insulin resistance) 3. Gestational diabetes mellitus (GDM) (diabetes diagnosed in the second or third trimester of pregnancy that is not clearly overt diabetes) 4. Specific types of diabetes due to other causes, e.g., monogenic diabetes syndromes (such as neonatal diabetes and maturity-onset diabetes of the young [MODY]), diseases of the exocrine pancreas (such as cystic fibrosis), and drugor chemical-induced diabetes (such as in the treatment of HIV/AIDS or after organ transplantation)

Classification and diagnosis of diabetes

Pancreatic cancer remains one of the most lethal of malignancies and a major health burden. We performed whole-genome sequencing and copy number variation (CNV) analysis of 100 pancreatic ductal adenocarcinomas (PDACs). Chromosomal rearrangements leading to gene disruption were prevalent, affecting genes known to be important in pancreatic cancer (TP53, SMAD4, CDKN2A, ARID1A and ROBO2) and new candidate drivers of pancreatic carcinogenesis (KDM6A and PREX2). Patterns of structural variation (variation in chromosomal structure) classified PDACs into 4 subtypes with potential clinical utility: the subtypes were termed stable, locally rearranged, scattered and unstable. A significant proportion harboured focal amplifications, many of which contained druggable oncogenes (ERBB2, MET, FGFR1, CDK6, PIK3R3 and PIK3CA), but at low individual patient prevalence. Genomic instability co-segregated with inactivation of DNA maintenance genes (BRCA1, BRCA2 or PALB2) and a mutational signature of DNA damage repair deficiency. Of 8 patients who received platinum therapy, 4 of 5 individuals with these measures of defective DNA maintenance responded.

Whole genomes redefine the mutational landscape of pancreatic cancer.

Understanding immune memory to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is critical for improving diagnostics and vaccines and for assessing the likely future course of the COVID-19 pandemic. We analyzed multiple compartments of circulating immune memory to SARS-CoV-2 in 254 samples from 188 COVID-19 cases, including 43 samples at ≥6 months after infection. Immunoglobulin G (IgG) to the spike protein was relatively stable over 6+ months. Spike-specific memory B cells were more abundant at 6 months than at 1 month after symptom onset. SARS-CoV-2-specific CD4+ T cells and CD8+ T cells declined with a half-life of 3 to 5 months. By studying antibody, memory B cell, CD4+ T cell, and CD8+ T cell memory to SARS-CoV-2 in an integrated manner, we observed that each component of SARS-CoV-2 immune memory exhibited distinct kinetics.

Immunological memory to SARS-CoV-2 assessed for up to 8 months after infection.

‡We describe the use of singular value decomposition in transforming genome-wide expression data from genes 3 arrays space to reduced diagonalized ‘‘eigengenes’’ 3 ‘‘eigenarrays’’ space, where the eigengenes (or eigenarrays) are unique orthonormal superpositions of the genes (or arrays). Normalizing the data by filtering out the eigengenes (and eigenarrays) that are inferred to represent noise or experimental artifacts enables meaningful comparison of the expression of different genes across different arrays in different experiments. Sorting the data according to the eigengenes and eigenarrays gives a global picture of the dynamics of gene expression, in which individual genes and arrays appear to be classified into groups of similar regulation and function, or similar cellular state and biological phenotype, respectively. After normalization and sorting, the significant eigengenes and eigenarrays can be associated with observed genome-wide effects of regulators, or with measured samples, in which these regulators are overactive or underactive, respectively.

Singular Value Decomposition for Genome-Wide Expression Data Processing and Modeling

In the omics era, saliva, a filtrate of blood, may serve as an alternative, noninvasive biospecimen to blood, although its use for specific metabolomic applications has not been fully evaluated. We demonstrated that the saliva metabolome may provide sensitive measures of traffic-related air pollution (TRAP) and associated biological responses via high-resolution, longitudinal metabolomics profiling. We collected 167 pairs of saliva and plasma samples from a cohort of 53 college student participants and measured corresponding indoor and outdoor concentrations of six air pollutants for the dormitories where the students lived. Grand correlation between common metabolic features in saliva and plasma was moderate to high, indicating a relatively consistent association between saliva and blood metabolites across subjects. Although saliva was less associated with TRAP compared to plasma, 25 biological pathways associated with TRAP were detected via saliva and accounted for 69% of those detected via plasma. Given the slightly higher feature reproducibility found in saliva, these findings provide some indication that the saliva metabolome offers a sensitive and practical alternative to blood for characterizing individual biological responses to environmental exposures.

Evaluation of the Use of Saliva Metabolome as a Surrogate of Blood Metabolome in Assessing Internal Exposures to Traffic-Related Air Pollution.

—The training of modern speech processing systems often requires a large amount of simulated room impulse response (RIR) data in order to allow the systems to generalize well in real- world, reverberant environments. However, simulating realistic RIR data typically requires accurate physical modeling, and the acceleration of such simulation process typically requires certain computational platforms such as a graphics processing unit (GPU). In this paper, we propose FRA-RIR, a fast random approximation method of the widely-used image-source method (ISM), to efﬁciently generate realistic RIR data without speciﬁc computational devices. FRA-RIR replaces the physical simulation in the standard ISM by a series of random approximations, which signiﬁcantly speeds up the simulation process and enables its application in on-the-ﬂy data generation pipelines. Experiments show that FRA-RIR can not only be signiﬁcantly faster than other existing ISM-based RIR simulation tools on standard computational platforms, but also improves the performance of speech denoising systems evaluated on real-world RIR when trained with simulated RIR. A Python implementation of FRA- RIR is available online 1 .

FRA-RIR: Fast Random Approximation of the Image-source Method

Despite the rapid progress in speech enhancement (SE) research, enhancing the quality of desired speech in environments with strong noise and interfering speakers remains challenging. In this paper, we extend the application of the recently proposed band-split RNN (BSRNN) model to full-band SE and personalized SE (PSE) tasks. To mitigate the effects of unstable high-frequency components in full-band speech, we perform bi-directional and uni-directional band-level modeling to low-frequency and high-frequency subbands, respectively. For PSE task, we incorporate a speaker enrollment module into BSRNN to utilize target speaker information. Moreover, we utilize a MetricGAN discriminator (MGD) and a multi-resolution spectrogram discriminator (MRSD) to improve perceptual quality metrics. Experimental results show that our system outperforms various top-ranking SE systems, achieves state-of-the-art (SOTA) results on the DNS-2020 test set and ranks among the top 3 in the DNS-2023 challenge.

High Fidelity Speech Enhancement with Band-split RNN

Two proteins share immunological epitopes on the tumor-associated antigen 17-1A

Nuclear magnetic resonance (NMR) spectroscopy, traditionally used in analytical chemistry, has recently been introduced to studies of metabolite composition of biological fluids and tissues. Metabolite levels change over time, and providing a tool for better extraction of NMR peaks exhibiting periodic behavior is of interest. We propose a method in which NMR peaks are clustered based on periodic behavior. Periodic regression is used to obtain estimates of the parameter corresponding to period for individual NMR peaks. A mixture model is then used to develop clusters of peaks, taking into account the variability of the regression parameter estimates. Methods are applied to NMR data collected from human blood plasma over a 24-hour period. Simulation studies show that the extra variance component due to the estimation of the parameter estimate should be accounted for in the clustering procedure.

Tianwei Yu

Papers

Evaluation of the Use of Saliva Metabolome as a Surrogate of Blood Metabolome in Assessing Internal Exposures to Traffic-Related Air Pollution.

FRA-RIR: Fast Random Approximation of the Image-source Method

High Fidelity Speech Enhancement with Band-split RNN

Two proteins share immunological epitopes on the tumor-associated antigen 17-1A

Clustering Based on Periodicity in High-Throughput Time Course Data