Statistical Methodology for Sequence Analysis

Rare disease variants are receiving increasing importance in the past few years as the potential cause for many complex diseases, after the common disease variants failed to explain a large part of the missing heritability. With the advancement in sequencing techniques as well as computational capabilities, statistical methodology for analyzing rare variants is now a hot topic, especially in case-control association studies. In this thesis, we initially present two related statistical methodologies designed for case-control studies to predict the number of common and rare variants in a particular genomic region underlying the complex disease. Genome-wide association studies are nowadays routinely performed to identify a few putative marker loci or a candidate region for further analysis. These methods are designed to work with SNP data on such a genomic region highlighted by GWAS studies for potential disease variants. The fundamental idea is to use Bayesian methodology to obtain bivariate posterior distributions on counts of common and rare variants. While the first method uses randomly generated (minimal) ancestral recombination graphs, the second method uses ensemble clustering method to explore the space of genealogical trees that represent the inherent structure in the test subjects. In contrast to the aforesaid methods which work with SNP data, the third chapter deals with next-generation sequencing data to detect the presence of rare variants in a genomic region. We present a non-parametric statistical methodology for rare variant association testing, using the well-known Kolmogorov-Smirnov framework adapted for genetic data. it is a fast, model-free robust statistic, designed for situations where both deleterious and protective variants are present. It is also unique in utilizing the variant locations in the test statistic

当代中国人群牙齿可观测特征的多样性研究

This study is based on 3D dental models of contemporary Chinese groups and dental landmarking methods used according to research protocols developed by the Consortium for the Analysis of the Diversity and Evolution of Latin America (CANDELA). Dental phenotypes represented by Euclidean linear distances (ELD) computed between landmarks are used to assess dental diversity. This study aims to explore the impact of individual factors (age and gender) and population factors (ethnic groups) on dental diversity among contemporary Chinese groups. The results of canonical variate analysis (CVA), cross-validated canonical variate analysis (CV), principal component analysis (PCA), Pearson correlation analyses, and biodistances showed that the dental observable characteristics of populations that had closer evolutionary relationships were often more similar. Specifically, the dental observable characteristics of the upper teeth of Han nationality are closer to those of Zhuang and Miao nationalities but different from those of Mongolian nationality, and the dental observable characteristics of upper and lower teeth of Tibetan nationality are different from those of Uyghur nationality. The biodistance differentiation in dental phenotypes of southern/ northern/ central Han Chinese was clearly directional (clines), and the differences in mandibular teeth were higher than those of maxillary teeth. From the perspective of gender, the differences in dental phenotypes between men and women were mainly reflected in the canines, and the average width and height of male canines were significantly greater than that of female canines. The analysis among different age groups showed that the influence of extragenetic factors on the dental observable characteristics was mainly reflected in the canines, maxillary first molars, and mandibular first premolars.本研究基于当代中国人群 3D 牙齿模型数据, 参照拉美人群进化和多样性研究联合会( consortium for the analysis of the diversity and evolution of Latin America, CANDELA)所使用的牙齿特征点标记方法, 使用牙齿特征点间的欧几里得线性距 离(Euclidean linear distances, ELD)表示的牙齿表型作为牙齿可观测特征的度量, 探究个体因素(年龄、 性别)和群体因素(民 族)对当代中国人群牙齿可观测特征多样性的影响。 通过对牙齿标记特征点的典型变量分析( canonical variate analysis, CVA)、 交叉验证(cross validation, CV)、 主成分分析(principal component analysis, PCA)以及对牙齿表型的 Pearson 相关性分 析和差异分析, 本研究发现进化上相近的群体牙齿可观测特征往往更接近。 具体来说, 汉族的上颌牙齿可观测特征和壮族、 苗族较为接近而不同于蒙古族的, 而藏族的上、 下颌牙齿可观测特征不同于维吾尔族的; 南北中汉族牙齿表型的差异具有明 确的方向性, 下颌牙齿差异比上颌更明显; 从性别角度看, 男女牙齿表型差异主要体现在尖牙上, 男性尖牙平均宽度和高度 显著大于女性的; 对不同年龄群体的差异分析表明, 遗传外因素对牙齿可观测特征的影响主要体现在尖牙、 上颌第一磨牙、 下颌第一前磨牙上。Fil: Hao, Luo. Fudan University; ChinaFil: Chen, Yingjie. Fudan University; ChinaFil: Yang, Guangrui. Fudan University; ChinaFil: Adhikari, Kaustubh. The Open University; Reino UnidoFil: Xia, Bin. Peking University; ChinaFil: Ruiz-Linares, Andres. Fudan University; ChinaFil: Delgado Burbano, Miguel Eduardo. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Área Antropológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentin

Human ratings of LLM response generation in pair-programming dialogue

We take first steps in exploring whether Large Language Models (LLMs) can be adapted to dialogic learning practices, specifically pair programming — LLMs have primarily been implemented as programming assistants, not fully exploiting their dialogic potential. We used new dialogue data from real pair-programming interactions between students, prompting state-of-the-art LLMs to assume the role of a student, when generating a response that continues the real dialogue. We asked human annotators to rate human and AI responses on the criteria through which we operationalise the LLMs’ suitability for educational dialogue: Coherence, Collaborativeness, and whether they appeared human. Results show model differences, with Llama-generated responses being rated similarly to human answers on all three criteria. Thus, for at least one of the models we investigated, the LLM utterance-level response generation appears to be suitable for pair-programming dialogue

Factors associated with hypertension in Pakistan: A systematic review and meta-analysis

Background: High blood pressure is an important public health concern and the leading risk factor for global mortality and morbidity. To assess the implications of this condition, we aimed to review the existing literature and study the factors that are significantly associated with hypertension in the Pakistani population.Methods: We conducted several electronic searches in PubMed, ISI Web of Science, PsycINFO, EMBASE, Scopus, Elsevier, and manually searched the citations of published articles on hypertension from May 2019 to August 2019. We included all studies that examined factors associated with hypertension regardless of the study design. To assess the quality of the research, we used the Newcastle-Ottawa Quality Assessment Scale. We also conducted meta-analyses using the DerSimonian & Laird random-effects model to collate results from at least three studies.Results: We included 30 cross-sectional and 7 case-control studies (99,391 participants country-wide) in this review and found 13 (35.1%) to be high-quality studies. We identified 5 socio-demographic, 3 lifestyle, 3 health-related, and 4 psychological variables that were significantly associated with hypertension. Adults aged between 30–60 years who were married, living in urban areas with high incomes, used tobacco, had a family history of hypertension, and had comorbidities (overweight, obesity, diabetes, anxiety, stress, and anger management issues) were positively associated with hypertension. On the other hand, individuals having high education levels, normal physical activity, and unrestricted salt in their diet were negatively associated with hypertension.Conclusion: We found several socio-demographic, lifestyle, health-related, and psychological factors that were significantly (positively and negatively) associated with hypertension. Our findings may help physicians and public health workers to identify high-risk groups and recommend appropriate prevention strategies. Further research is warranted to investigate these factors rigorously and collate global evidence on the same

Exploring The Diversity Of Our Skin

This report will discuss the process of collecting skin tone measurements from a diverse group of participants and analyse the accuracies of machine-based readings through comparing with reference measurements. The machines usually take the readings of the skin tone level by generating the images and analysing them with various statistical techniques to read the information received. Most methods used today can be completed using machines and technology and we have taken advantage of this by obtaining image samples of the participants faces or/and parts of their arms and have the image processed by self-created algorithm to get the colour values of each image sample for every sample given. Instead of the results received being based on societies ethnicities the colours are received in RGB (red, green, and blue) reflectance values with a median number between 0 and 255 for each image sample processed. Using this information, we can observe the accuracy that is assumed for the machine to have when reading the skin tone of a range of skin tones and use the results as a basis to improve accuracy in machines when it comes to recognising those of a darker skin tone removing the Caucasian bias within them

Genetic components of human pain sensitivity: a protocol for a genome-wide association study of experimental pain in healthy volunteers

International audiencePain constitutes a major component of the global burden of diseases. Recent studies suggest a strong genetic contribution to pain susceptibility and severity. Whereas most of the available evidence relies on candidate gene association or linkage studies, research on the genetic basis of pain sensitivity using genome-wide association studies (GWAS) is still in its infancy. This protocol describes a proposed GWAS on genetic contributions to baseline pain sensitivity and nociceptive sensitisation in a sample of unrelated healthy individuals of mixed Latin American ancestry

Meta-analysis of genome-wide association studies identifies 8 novel loci involved in shape variation of human head hair

Shape variation of human head hair shows striking variation within and between human populations, while its genetic basis is far from being understood. We performed a series of genome-wide association studies (GWASs) and replication studies in a total of 28 964 subjects from 9 cohorts from multiple geographic origins. A meta-analysis of three European GWASs identified 8 novel loci (1p36.23

Automatic landmarking identifies new loci associated with face morphology and implicates Neanderthal introgression in human nasal shape

We report a genome-wide association study of facial features in >6000 Latin Americans based on automatic landmarking of 2D portraits and testing for association with inter-landmark distances. We detected significant associations (P-value <5 × 10−8) at 42 genome regions, nine of which have been previously reported. In follow-up analyses, 26 of the 33 novel regions replicate in East Asians, Europeans, or Africans, and one mouse homologous region influences craniofacial morphology in mice. The novel region in 1q32.3 shows introgression from Neanderthals and we find that the introgressed tract increases nasal height (consistent with the differentiation between Neanderthals and modern humans). Novel regions include candidate genes and genome regulatory elements previously implicated in craniofacial development, and show preferential transcription in cranial neural crest cells. The automated approach used here should simplify the collection of large study samples from across the world, facilitating a cosmopolitan characterization of the genetics of facial features

A geometric morphometric approach to the study of variation of shovel-shaped incisors

International audienc

A geometric morphometric approach to the study of variation of shovel-shaped incisors

Objectives: The scoring and analysis of dental nonmetric traits are predominantly accomplished by using the Arizona State University Dental Anthropology System (ASUDAS), a standard protocol based on strict definitions and three‐dimensional dental plaques. However, visual scoring, even when controlled by strict definitions of features, visual reference, and the experience of the observer, includes an unavoidable part of subjectivity. In this methodological contribution, we propose a new quantitative geometric morphometric approach to quickly and efficiently assess the variation of shoveling in modern human maxillary central incisors (UI1). Materials and methods: We analyzed 87 modern human UI1s by means of virtual imaging and the ASU‐UI1 dental plaque grades using geometric morphometrics by placing semilandmarks on the labial crown aspect. The modern human sample was composed of individuals from Europe, Africa, and Asia and included representatives of all seven grades defined by the ASUDAS method. Results: Our results highlighted some limitations in the use of the current UI1 ASUDAS plaque, indicating that it did not necessarily represent an objective gradient of expression of a nonmetric tooth feature. Rating of shoveling tended to be more prone to intra‐ and interobserver bias for the highest grades. In addition, our analyses suggest that the observers were strongly influenced by the depth of the lingual crown aspect when assessing the shoveling. Discussion: In this context, our results provide a reliable and reproducible framework reinforced by statistical results supporting the fact that open scale numerical measurements can complement the ASUDAS method