A flexible computational framework for detecting, characterizing, and interpreting statistical patterns of epistasis in genetic studies of human disease susceptibility

Detecting, characterizing, and interpreting gene-gene interactions or epistasis in studies of human disease susceptibility is both a mathematical and a computational challenge. To address this problem, we have previously developed a multifactor dimensionality reduction (MDR) method for collapsing high-dimensional genetic data into a single dimension (i.e. constructive induction) thus permitting interactions to be detected in relatively small sample sizes. In this paper, we describe a comprehensive and flexible framework for detecting and interpreting gene-gene interactions that utilizes advances in information theory for selecting interesting single-nucleotide polymorphisms (SNPs), MDR for constructive induction, machine learning methods for classification, and finally graphical models for interpretation. We illustrate the usefulness of this strategy using artificial datasets simulated from several different two-locus and three-locus epistasis models. We show that the accuracy, sensitivity, specificity, and precision of a na?ve Bayes classifier are significantly improved when SNPs are selected based on their information gain (i.e. class entropy removed) and reduced to a single attribute using MDR. We then apply this strategy to detecting, characterizing, and interpreting epistatic models in a genetic study (n = 500) of atrial fibrillation and show that both classification and model interpretation are significantly improved.     

基于多目标的杨树速生丰产林主伐决策分析

经济效益综合评价是产业决策研究的重要内容.从系统工程观点来看,经济效益综合评价本质上是一个有限方案多目标决策问题.因此,本文采用多目标决策法对杨树速生丰产林的主伐决策进行研究,以年均净现值、内部收益率、土地期望价、效益成本比、成本利润率为指标,提出用熵技术法确定评价指标权重,结合"理想点"法、TOPSIS法和线性加权和法三种方法对决策方案进行排序择优,得到不同排序结果,最后用平均值法得到最终综合评价结果.结果表明,对所研究的密度为10×10m~2、8×8m~2、6×8m~2、5×6m~2的杨速生丰产林进行分析得到综合评价结果,其最优主伐龄分别为:13年、10年、9年、9年.随着密度的增大,经济成熟龄提前.本研究表明该方法对杨树速生丰产林的主伐决策研究是有效可行的.     

利用最大熵模型和规则集遗传算法模型预测孑遗植物裸果木的潜在地理分布及格局

利用野外调查的16个居群分布点和7个环境因子图层, 选择最大熵模型(MAXENT)和规则集遗传算法模型(GARP), 在地理和环境空间上模拟了第三纪孑遗植物裸果木(Gymnocarpos przewalskii)在中国西北地区的潜在分布。结果表明: (1)裸果木的潜在适生区全部集中在西北荒漠区, 其中最佳适生区主要集中在3个区域, 一是河西走廊中部和玉门以西、宁夏北部及内蒙古乌拉特后旗; 二是塔里木盆地西北缘; 三是柴达木盆地西北缘两片极小的高度适生区。裸果木的生态位被确定在一个较广的干旱环境空间: 适生区极端最高气温基本上在29.2-36.8 ℃之间, 极端最低气温在-18.3至-13.4 ℃之间; 年平均降水量40-200 mm; 潜在蒸发率在3-15之间。(2) MAXENT和GARP模型都较好地预测了裸果木的潜在分布, 但GARP产生了相对较大、较连续的潜在分布区, 部分过预测了破碎化生境; 而MAXENT预测到的潜在分布区, 在不同区域具有不同的环境适生性指数, 而且成功地排除了不合理的破碎化分布, 从而更直观地展示了裸果木的潜在分布格局和生态位要求。     

Perspective: Researching the transition from non-living to the first microorganisms: Methods and experiments are major challenges

Methods to research the origin of microbial life are limited. However, microorganisms were the first organisms on the Earth capable of cell growth and division, and interactions with their environment, other microbial cells, and eventually with diverse eukaryotic organisms. The origin of microbial life and the supporting scientific evidence are both an enigma and a scientific priority. Numerous hypotheses have been proposed, scenarios imagined, speculations presented in papers, insights shared, and assumptions made without supporting experimentation, which have led to limited progress in understanding the origin of microbial life. The use of the human imagination to envision the origin of life events, without supporting experimentation, observation and independently replicated experiments required for science, is a significant constraint. The challenge remains how to better understand the origin of microbial life using observations and experimental methods as opposed to speculation, assumptions, scenarios, envisioning events and un-testable hypotheses. This is not an easy challenge as experimental design and plausible hypothesis testing are difficult. Since past approaches have been inconclusive in providing evidence for the origin of microbial life mechanisms and the manner in which genetic instructions was encoded into DNA/RNA, it is reasonable and logical to propose that progress will be made when testable, plausible hypotheses and methods are used in the origin of microbial life research, and the experimental observations are, or are not reproduced in independent laboratories. These perspectives will be discussed in this article as well as the possibility that a pre-biotic film preceded a microbial biofilm as a possible micro-location for the origin of microbial cells capable of growth and division.     

Are bird song complexity and song sharing shaped by habitat structure? An information theory and statistical approach

In songbirds, song complexity and song sharing are features of prime importance for territorial defence and mate attraction. These aspects of song may be strongly influenced by changes in social environment caused by habitat fragmentation. We tested the hypothesis that habitat fragmentation induced by human activities influences song complexity and song sharing in the skylark, a songbird with a very large repertoire and whose population recently underwent a large decline. We applied powerful mathematical and statistical tools to assess and compare song complexity and song sharing patterns of syllables and sequences of syllables in two populations: a declining population in a fragmented habitat, in which breeding areas are separated from each other by unsuitable surroundings, and a stable population in a continuous habitat. Our results show that the structure of the habitat influences song sharing, but not song complexity. Neighbouring birds shared more syllables and sequences of syllables in the fragmented habitat than in the continuous one. Habitat fragmentation seems thus to have an effect on the composition of elements in songs, but not on the number and complexity of these elements, which may be a fixed feature of song peculiar to skylarks.     

Information capacity of nucleotide sequences and Its applications

The information capacity of nucleotide sequences is defined through the specific entropy of frequency dictionary of a sequence determined with respect to another one containing the most probable continuations of shorter strings. This measure distinguishes a sequence both from a random one, and from ordered entity. A comparison of sequences based on their information capacity is studied. An order within the genetic entities is found at the length scale ranged from 3 to 8. Some other applications of the developed methodology to genetics, bioinformatics, and molecular biology are discussed.     

HIV-1 GP120 V3 conformational and informational entropies

In an attempt to analyze structure, function and evolution of HIV-1 GP120 V3, interactions among the Hartree–Fock energy, the conformational entropy and the Shannon entropy were determined for the 1NJ0 set of antibody-bound V3 loop conformers. The Hartree–Fock energy of each conformer was determined at the MINI level with GAMESS. The conformational entropy was determined per conformer and per residue from the mass-weighted covariance matrices. The Shannon entropy per residue was determined from sequence-substitution frequencies. Correlations were determined by linear regression analysis. There was a negative correlation between the Hartree–Fock energy and the conformational entropy (R=−0.4840, p=0.0078, df =28) that enhanced the negative Helmholtz-free-energy change for the binding of the GP120 ligand to target CD4. The Shannon entropy of V3 was a function of the conformational entropy variance (R=0.7225, p=0.00157, df=15) and of the V3 Hartree–Fock energy. Biological implications of this work are that (1) conformational entropy interacts with V3 Hartree–Fock energy to enhance GP120 binding to CD4 cell receptors and that (2) the Hartree–Fock energy of V3 interacts with the evolutionary system to participate in the regulation of V3 diversity.     

Biological models: measuring variability with classical and quantum information

This essay proposes methods to analyse the variability of biological data. The idea is to express the state of a biological system as a linear combination of base states in a Hilbert space. Coefficients of the linear combination can be interpreted as probabilities and informational entropy is associated to each state allowing the definition of a classical variability measure. Besides, state transition matrices can also be calculated and their norms express the dynamics of the system organization and a quantum variability measure. As the examples show, the classical measure expresses a structural variability and the quantum measure expresses a functional variability.     

一株GⅠ.3[P13]型诺如病毒的全基因组序列分析

诺如病毒(Norovirus,NoV)是人类非菌性急性肠胃炎的主要病原,GⅠ和GⅡ基因群在人类中流行较广,但对GⅠ群少有研究。为分析西安市2018年一株GⅠ型诺如病毒CHN/Xian/18N239的全基因组基因特征,本研究对某幼儿园急性肠胃炎病例肛拭子检出的一株GⅠ型诺如病毒,使用下一代测序方法对其全基因组测序,用Blastn比对和诺如病毒在线定型工具分析CHN/Xian/18N239的基因型,用MEGA-X对其进化分析,用Bioedit对其同源性、氨基酸变异和熵值进行计算,并用SWⅠSS-MODEL和PyMOL2.3.2预测和可视化三维结构。CHN/Xian/18N239株全长7684 nt,开放阅读框(ORF)1~3分别长5316 nt(84~5399 nt)、1635 nt(5383~7017 nt)和648 nt(7017~7664nt),ORF1和ORF2的重叠区长17 nt。Blastn比对显示其与GⅠ.3[P13]型2019年中国台湾株(MN922738)核苷酸同源性最高(98.91%)。系统进化分析表明其为GⅠ.3[P13]型,与韩国2017-2018年、中国台湾2018-2019年流行株核苷酸同源性为98.7%~99.3%。与参考序列U04469比,变异位点共75个,主要在P2区,其中在人外周血抗原结合位点Ⅱ有1个,且在A-Loop、T-loop、U-loop和S-loop区的三维结构改变较大。VP2区熵值为0的位点最少,VP1区易突变位点最多。应加强对本地区诺如病毒分子型别监测,提高防控能力。     

Bits and q-bits in a psychiatric ward

The present study is a trial on expressing the whole state of a psychiatric ward as a linear combination of base states in a Hilbert space. Real data were collected by observing the behavior of the patients from the psychiatric ward of the Clinical Hospital from Faculdade de Medicina de Ribeir?o Preto for 12 days and, according to standard procedures, 18 behavioral parameters were daily measured for each patient. The whole data set was analyzed and, by taking the standard grades as eigenstates, the state of the ward was daily expressed by a linear combination of them, allowing the estimation of state transition matrices and of the quantum variability measure. Coefficients of the linear combination can be interpreted as square roots of probabilities and informational entropy is associated to each state resulting in the classical variability measure. Temporal evolutions of the classical and quantum variability measures are plotted trying to relate them to the behavioral state of the whole ward.