arXiv subjects

Guoqiang Yu

Publications and source records attributed to Guoqiang Yu.

60 records · Page 4Linked to original sources

arXiv2015

Asymmetric Independence Model for Detecting Interactions between Variables

Detecting complex interactions among risk factors in case-control studies is a fundamental task in clinical and population research. However, though hypothesis testing using logistic regression (LR) is a convenient solution, the LR framework is poorly powered and ill-suited under several common circumstances in practice including missing or unmeasured risk factors, imperfectly correlated "surrogates", and multiple disease sub-types. The weakness of LR in these settings is related to the way in which the null hypothesis is defined. Here we propose the Asymmetric Independence Model (AIM) as a biologically-inspired alternative to LR, based on the key observation that the mechanisms associated with acquiring a "disease" versus maintaining "health" are asymmetric. We prove mathematically that, unlike LR, AIM is a robust model under the abovementioned confounding scenarios. Further, we provide a mathematical definition of a "synergistic" interaction, and prove that theoretically AIM has better power than LR for such interactions. We then experimentally show the superior performance of AIM as compared to LR on both simulations and four real datasets. While the principal application here involves genetic or environmental variables in the life sciences, our methodology is readily applied to other types of measurements and inferences, e.g. in the social sciences.

stat.ME↗

arXiv2014

A feasible roadmap to identifying significant intercellular genomic heterogeneity in deep sequencing data

Intercellular heterogeneity serves as both a confounding factor in studying individual clones and an information source in characterizing any heterogeneous tissues, such as blood, tumor systems. Due to inevitable sequencing errors and other sample preparation artifacts such as PCR errors, systematic efforts to characterize intercellular genomic heterogeneity must effectively distinguish genuine clonal sequences from fake derivatives. We developed a novel approach (SIGH) for identifying significant genuine clonal sequences directly from mixed sequencing reads that can improve genomic analyses in many biological contexts. This method offers several attractive features: (1) it automatically estimates the error rate from raw sequence reads and identifies genuine clonal sequences; (2) it is robust to the large variety of error rate due to the various experimental conditions; (3) it is supported by a well grounded statistical framework that exploits probabilistic characteristics of sequencing errors; (4) its unbiased strategy allows detecting rare clone(s) despite that clone relative abundance; and (5) it estimates constituent proportions in each sample. Extensive realistic simulation studies show that our method can reliably estimate the error rates and faithfully distinguish the genuine clones from fake derivatives, paving the way for follow up analysis that is otherwise ruined by the often dominant fake clones.

q-bio.GN↗

arXiv2014

A Statistical Approach to Identifying Significant Transgenerational Methylation Changes

Epigenetic aberrations have profound effects on phenotypic output. Genome wide methylation alterations are inheritable to pass down the aberrations through multiple generations. We developed a statistical method, Genome-wide Identification of Significant Methylation Alteration, GISAIM, to study the significant transgenerational methylation changes. GISAIM finds the significant methylation aberrations that are inherited through multiple generations. In a concrete biological study, we investigated whether exposing pregnant rats (F0) to a high fat (HF) diet throughout pregnancy or ethinyl estradiol (EE2)-supplemented diet during gestation days 14 20 affects carcinogen-induced mammary cancer risk in daughters (F1), granddaughters (F2) and great-granddaughters (F3). Mammary tumorigenesis was higher in daughters and granddaughters of HF rat dams, and in daughters, granddaughters and great-granddaughters of EE2 rat dams. Outcross experiments showed that increased mammary cancer risk was transmitted to HF granddaughters equally through the female or male germlines, but is only transmitted to EE2 granddaughters through the female germline. Transgenerational effect on mammary cancer risk was associated with increased expression of DNA methyltransferases, and across all three EE2 generations hypo or hyper methylation of the same 375 gene promoter regions in their mammary glands. Our study shows that maternal dietary estrogenic exposures during pregnancy can increase breast cancer risk in multiple generations of offspring, and the increase in risk may be inherited through non-genetic means, possibly involving DNA methylation.

q-bio.QM↗

arXiv2014

BACOM 2.0 facilitates absolute normalization and quantification of somatic copy number alterations in heterogeneous tumor

BACOM is a statistically principled and unsupervised method that detects copy number deletion types (homozygous versus heterozygous), estimates normal cell fraction, and recovers cancer specific copy number profiles, using allele specific copy number signals. In a subsequent analysis of TCGA ovarian cancer dataset, the average normal cell fraction estimated by BACOM was found higher than expected. In this letter, we first discuss the advantages of the BACOM in relation to alternative approaches. Then, we show that this elevated estimate of normal cell fraction is the combined result of inaccurate signal modeling and normalization. Lastly, we describe an allele specific signal modeling and normalization scheme that can enhance BACOM applications in many biological contexts. An open source MATLAB program was developed to implement our extended method and it is publically available.

q-bio.GN↗

arXiv2013

Switching of perpendicular magnetization by spin-orbit torques in the absence of external magnetic fields

Magnetization switching by current-induced spin-orbit torques (SOTs) is of great interest due to its potential applications for ultralow-power memory and logic devices. In order to be of technological interest, SOT effects need to switch ferromagnets with a perpendicular (out-of-plane) magnetization. Currently, however, this typically requires the presence of an in-plane external magnetic field, which is a major obstacle for practical applications. Here we report for the first time on SOT-induced switching of out-of-plane magnetized Ta/Co20Fe60B20/TaOx structures without the need for any external magnetic fields, driven by in-plane currents. This is achieved by introducing a lateral structural asymmetry into our devices during fabrication. The results show that a new field-like SOT is induced by in-plane currents in such asymmetric structures. The direction of the current-induced effective field corresponding to this new field-like SOT is out-of-plane, which facilitates switching of perpendicular magnets. This work thus provides a pathway towards bias-field-free SOT devices.

cond-mat.mes-hall↗

arXiv2013

A feasible roadmap for unsupervised deconvolution of two-source mixed gene expressions

Tissue heterogeneity is a major confounding factor in studying individual populations that cannot be resolved directly by global profiling. Experimental solutions to mitigate tissue heterogeneity are expensive, time consuming, inapplicable to existing data, and may alter the original gene expression patterns. Here we ask whether it is possible to deconvolute two-source mixed expressions (estimating both proportions and cell-specific profiles) from two or more heterogeneous samples without requiring any prior knowledge. Supported by a well-grounded mathematical framework, we argue that both constituent proportions and cell-specific expressions can be estimated in a completely unsupervised mode when cell-specific marker genes exist, which do not have to be known a priori, for each of constituent cell types. We demonstrate the performance of unsupervised deconvolution on both simulation and real gene expression data, together with perspective discussions.

stat.ML↗