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1.
Fabrice Berger Benoît De Hertogh Michaël Pierre Anthoula Gaigneaux Eric Depiereux 《Central European Journal of Biology》2008,3(3):327-344
This work focuses on differential expression analysis of microarray datasets. One way to improve such statistical analyses
is to integrate biological information in the design of these analyses. In this paper, we will use the relationship between
the level of gene expression and variability. Using this biological information, we propose to integrate the information from
multiple genes to get a better estimate of individual gene variance, when a small number of replicates are available, to increase
the power of the statistical analysis. We describe a strategy named the “Window t test” that uses multiple genes which share a similar expression level to compute the variance which is then incorporated
a classic t test. The performances of this new method are evaluated by comparison with classic and widely-used methods for differential
expression analysis (the classic Student t test, the Regularized t test (reg t test), SAM, Limma, LPE and Shrinkage t). In each case tested, the results obtained were at least equivalent to the best performing method and, in most cases, outperformed
it. Moreover, the Window t test relies on a very simple procedure requiring small computing power compared with other methods designed for microarray
differential expression analysis.
Electronic Supplementary Material Supplementary material is available for this article at and is accessible for authorized users. 相似文献
2.
Tatiana Barkova Paul Comtois Zave Chad John Weisnagel André Caron Jaime Del Carpio Guérin Dorval John Schulz Lorne Umemoto Yves Charbonneau David Copeland 《Aerobiologia》1995,11(2):119-128
The purpose of this epidemiological study was to assess respiratory allergy in relation to the presence of indoor airborne
fungi. The relationship between IgE-mediated respiratory allergy (skin test positivity) and the presence of fungi (CFU/m3) in the indoor environments of 104 subjects was assessed in a cross-sectional study by controlling for extraneous variables
(age, gender, predisposition, asthma, rhinitis, skin positivity to ragweed and mite, and smoking). The qualitative and quantitative
measurements of airborne seasonal fungi (Alternaria spp. andCladosporium spp.) and non-seasonal airborne fungi (Penicillium spp. andAspergillus spp.) were taken in the subjects’ indoor environments twice in a 2-year period by volumetric methods (Burkard Personal Sampler).
There was a significant association between skin test positivity to seasonal fungi and to ragweed (Adj. OR=3.42, CI=1.76–6.66).
There was no association between skin test positivity to seasonal fungi and asthma (Adj. OR=0.52, CI=0.28–0.98), but a significant
association was found between skin test positivity to seasonal fungi and rhinitis (Adj. OR=5, CI=2.03–12.32). In a logistic
regression analysis (maximum likelihood estimates—model A), no statistical association was found indoors between skin prick
test positivity to seasonal fungi (Alternaria and/orCladosporium) and airborneAlternaria and/orCladosporium concentrations (Adj. OR=1.18, CI=0.66–2.07). There was a significant association between skin prick test positivity to seasonal
fungi and to non-seasonal fungi (Adj. OR=12.81, CI=1.67–98.34). There was no association between asthma and airbornePenicillium concentrations (Adj. OR=1.86, CI=0.47–7.33) nor between rhinitis and airbornePenicillium concentrations (Adj. OR=0.18, CI=0.03–1.19). In another logistic regression analysis (maximum likelihood estimates — model
B) using non-seasonal fungi (Aspergillus andPenicillium), no statistical association was found indoors between skin prick test positivity to non-seasonal fungi and airbornePenicillium concentrations (Adj. OR=0.33, CI=0.07–1.69). These findings suggest an association between rhinitis and seasonal fungi. In
the rhinitis stratum, subjects who had skin test positivity to ragweed had a higher risk of being sensitive to seasonal airborne
fungal allergens. Subjects with non-seasonal fungal allergy had a high relative risk if they were also allergic to seasonal
fungi. There was no association between asthma and airborne fungi, as the epidemiological study (cross-sectional design),
by definition, does not allow an etiological evaluation of chronic disease. This would require a longitudinal study, i.e.
the measurement of repeated exposure as an independent variable (allergen) and repeated measurement as a function of the disease
as outcome in humans as a dependent variable. 相似文献
3.
J. Oosterom C. H. den Uyl J. R. J. Bänffer S. Lauwers J. Huismans A. E. Busschbach F. G. J. Poelma R. Bellemans 《Antonie van Leeuwenhoek》1985,51(3):321-331
An enzyme-linked immunosorbent assay (ELISA) was developed for the detection of total anti-Campylobacter immunoglobulins in human sera. In this assay disintegratedCampylobacter bacteria were used as the antigen. Absorption tests including other possibly enteropathogenic bacterial species showed that
the ELISA system displayed a high immunological specificity forCampylobacter. Using this ELISA it was found that in about 80% ofCampylobacter patients theseCampylobacter antibodies are produced to almost maximal levels within 8 days after onset of disease, and that they may persist for at least
4 months. Indeed,Campylobacter antibodies were demonstrated at low levels in a large number of control sera. However, accepting an antibody titre of 1:
640 as indicative ofCampylobacter infection, the statistical sensitivity of the ELISA system was 77% and the specificity 95%. In an epidemiological survey
a high association was demonstrated between the severity ofCampylobacter-related symptoms and antibody titre values. Assessment ofCampylobacter antibody titres by means of this ELISA and by a complement fixation test in 92 sera from index patients and contacts with
and without symptoms showed a high association of results. 相似文献
4.
Yoshimoto Saitoh Kosuke Izumitsu Atsushi Morita Chihiro Tanaka 《Molecular genetics and genomics : MGG》2010,284(1):33-43
Copper is an essential trace element that serves as a cofactor for numerous enzymes. In eukaryotes, copper-transporting ATPases
deliver copper to various copper-containing proteins in the trans-golgi network. This study identified a copper-transporting ATPase gene BcCcc2 in a fungus pathogenic to plants, Botrytis cinerea. We investigated the biological roles of BcCCC2 by generating null mutants for BcCcc2. Melanization, conidiation and the formation of sclerotia were severely affected in ∆BcCcc2 mutants. Moreover, a pathogenicity assay using tomato leaves and carnation petals revealed the mutants to be nonpathogenic.
Further analysis indicated that they formed fewer appressoria and infection cushions than the wild-type. These structures
were aberrant in morphology and in many cases had a significantly reduced ability to penetrate the plant epidermis. An assay
also indicated that ∆BcCcc2 mutants were defective in infection through wounds. BcCCC2 is necessary not only for penetrating a host but also for fungal
growth within plant tissues. Our results also imply that B. cinerea requires copper-containing proteins for infection that are inactive in the absence of the copper-transporting ATPase BcCCC2. 相似文献
5.
Generation of white mold disease-resistant sunflower plants expressing human lysozyme gene 总被引:1,自引:0,他引:1
Sunflower plants were transformed via co-cultivation of previously bombarded hypocotyl explants with Agrobacterium tumefaciens harboring the plasmid pNGL that contains the human lysozyme gene. The transformed shoots were selected using kanamycin and
regenerated plants were analyzed using histochemical β-glucuronidase assay. Southern, Western and Northern blot analyses indicated
the transfer, expression and stable integration of the foreign DNA into the sunflower genome. Resistance against the phytopathogenic
fungus Sclerotinia sclerotiorum, which causes white mold disease, was confirmed using a phytopathogenic test and microscopic observation of the infection
process. 相似文献
6.
Pythium porphyrae is a fungal pathogen responsible for red rot disease of the seaweed Porphyra (Rhodophyta). Infection forecasts of Porphyra by P. porphyrae were estimated from the epidemiological observations of Porphyra thalli and numbers of zoospore of P. porphyrae in laboratory and cultivation areas. Four features of forecasting infections were determined by relating zoospore concentrations to the incidence of thallus infection; infection (in more than 1000 zoospores L−1), microscopic infection [less than 2 mm in diameter of lesion (in from 2000 to 3000 zoospores L−1)], macroscopic infection [more than 2 mm in diameter of lesion (in from 3000 to 4000 zoospores L−1), and thallus disintegration (in more than 4000 zoospores L−1). High zoospore concentrations led to more infection. The tendency that zoospore concentration of P. porphyrae increased with the rate of infection of Porphyra thalli was generally observed in forecasting infections in both the laboratory and in cultivation areas. Based on the Porphyra cultivation areas, the accuracy and consistency of forecasting infections suggest that this method could be employed to manage and control red rot disease. 相似文献
7.
8.
Michael R. Pears Denis Rubtsov Hannah M. Mitchison Jonathan D. Cooper David A. Pearce Russell J. Mortishire-Smith Julian L. Griffin 《Metabolomics : Official journal of the Metabolomic Society》2007,3(2):121-136
Using an NMR based approach, employing both solution state and high resolution magic angle spinning (HR MAS) 1H NMR spectroscopy, in conjunction with an array of statistical methods, we report cerebral metabolic deficits in a mouse
model of Batten disease (Cln3 null mutant mice). Batten disease is the most common progressive neurodegenerative disorder of childhood and is caused by
mutations in the Cln3 gene. In particular, brain tissue from Cln3 mice was characterised by increased concentrations of glutamine, myo-inositol, scyllo-inositol, aspartate and lactate, alongside
decreased concentrations of N-acetyl-l-aspartate (NAA), N-acetyl-l-glutamate (NAG), γ-amino butyric acid (GABA), glutamate and creatine. Accompanying changes in lipid deposition were also
detected in intact cortical tissue by HR MAS 1H NMR spectroscopy. To realise the true potential of metabolomic datasets necessitates a comprehensive analysis of the data,
such that useful biological information can be extracted and used to generate hypotheses which can be further tested and refined.
We found that using a combination of univariate and multivariate analyses, a maximal number of metabolic deficits were successfully
identified. In particular the complementary nature of the statistical approaches allowed the definition of changes which were
relative, absolute or simply a change in variance, allowing a greater understanding of the disease processes detected. 相似文献
9.
Chromoblastomycosis is a subcutaneous fungal disease caused by dematiaceous fungi, especially by Fonsecaea pedrosoi, regarded as its major causative agent in Brazil. In recent years there has been a decline in the use of skin testing for
delayed-type hypersensitivity (DTH) in epidemiological surveys of fungal infections, mainly because of the unpredictability
of positive reactions and lack of specificity of the antigens used. The aim of the present study was to assess delayed-type
skin tests in guinea pigs experimentally infected with F. pedrosoi using exoantigens prepared from two culture filtrates. Sixteen adult male guinea pigs were inoculated intratesticularly with
fungal cells and submitted to sensitivity assays 4 weeks after inoculation. They received an intradermal injection with crude
and fractionated antigens from Alviano’s and Smith’s cultures, and were assessed 24 and 48 h thereafter. Except for one animal,
all of them had positive indurations after 48 h. There were no statistical differences between the measurements at 24 and
48 h for each exoantigen used, neither among the induration measurements at 48 h when different preparations were compared.
Our results suggest that a delayed-type skin test using antigens produced in synthetic media may be useful for the assessment
of primary exposure to chromoblastomycosis. 相似文献
10.
【目的】对桑椹灾害性真菌病害——桑椹肥大性菌核病病原菌,即桑实杯盘菌(Ciboria shiraiana)的生物学特性进行研究,分析其流行性。【方法】采用人工接种、调查等研究方法,对C.shiraiana在无性生长阶段中菌丝侵染能力,菌核的休眠期,有性生长阶段中子囊孢子的结构、释放、数目以及萌发等进行研究,并对菌核萌发的物候期进行调查。【结果】C.shiraiana菌丝对桑雌花没有侵染能力;C.shiraiana菌核具有休眠期,低温处理6周以上的菌核才能萌发形成子囊盘;1个菌核可萌发1–15个子囊盘,直径为1.5 cm的子囊盘能产生高达(5.6–6.3)×10~7个子囊孢子;C.shiraiana子囊孢子在酸性环境中的萌发率明显高于在中性和碱性环境中的萌发率;C.shiraiana菌核萌发形成子囊盘产生子囊孢子的物候期,从1月下旬开始到4月中旬结束,其中在3月中旬萌发子囊盘的数目达到最高值。【结论】桑椹肥大性菌核病属于典型的流行性侵染病,在果桑栽培上容易造成毁灭性危害,生产上必须高度重视该病的防控。 相似文献
11.
Nakayama EE Carpentier W Costagliola D Shioda T Iwamoto A Debre P Yoshimura K Autran B Matsushita S Theodorou I 《Immunogenetics》2007,59(6):511-515
Polymorphisms in human genes have been shown to affect the rate of disease progression to acquired immune deficiency syndrome
in human immunodeficiency virus type 1 (HIV-1)-infected individuals. Recently, tripartite motif 5α (TRIM5α) was identified
as a factor that confers resistance to HIV-1 infection in Old World monkey cells. Subsequently, Sawyer et al. (Curr Biol 16:95–100,
2006) reported a single nucleotide polymorphism (H43Y) in the human TRIM5α gene and TRIM5α protein with 43Y was found to lose its ability to restrict HIV-1. In the present study, we reevaluated effects
of this allele on in vitro anti-HIV-1 activity as well as on HIV-1 disease progression in European and Asian cohorts of HIV-1-infected
individuals. Our epidemiological and molecular biological findings clearly indicate H43Y has a very minor effect on anti-HIV-1
activity of TRIM5α, suggesting that this allele is immaterial, at least in HIV-1-infected Europeans and Asians. 相似文献
12.
A host’s first line of defense in response to the threat of parasitic infection is behavior, yet the efficacy of anti-parasite
behaviors in reducing infection are rarely quantified relative to immunological defense mechanisms. Larval amphibians developing
in aquatic habitats are at risk of infection from a diverse assemblage of pathogens, some of which cause substantial morbidity
and mortality, suggesting that behavioral avoidance and resistance could be significant defensive strategies. To quantify
the importance of anti-parasite behaviors in reducing infection, we exposed larval Pacific chorus frogs (Pseudacris
regilla) to pathogenic trematodes (Ribeiroia and Echinostoma) in one of two experimental conditions: behaviorally active (unmanipulated) or behaviorally impaired (anesthetized). By quantifying
both the number of successful and unsuccessful parasites, we show that host behavior reduces infection prevalence and intensity
for both parasites. Anesthetized hosts were 20–39% more likely to become infected and, when infected, supported 2.8-fold more
parasitic cysts. Echinostoma had a 60% lower infection success relative to the more deadly Ribeiroia and was also more vulnerable to behaviorally mediated reductions in transmission. For Ribeiroia, increases in host mass enhanced infection success, consistent with epidemiological theory, but this relationship was eroded
among active hosts. Our results underscore the importance of host behavior in mitigating disease risk and suggest that, in
some systems, anti-parasite behaviors can be as or more effective than immune-mediated defenses in reducing infection. Considering
the severe pathologies induced by these and other pathogens of amphibians, we emphasize the value of a broader understanding
of anti-parasite behaviors and how co-occurring stressors affect them. 相似文献
13.
Dongdong Di Buyun Cui Heng Wang Hongyan Zhao Dongri Piao Lili Tian Guozhong Tian Jingli Kang Xiang Mao Xiaojun Zhang Pengfei Du Lin Zhu Zhuo Zhao Lingling Mao Wenqing Yao Pingyuan Guan Weixing Fan Hai Jiang 《PloS one》2014,9(1)
In China, brucellosis is an endemic disease typically caused by Brucella melitensis infection (biovars 1 and 3). Brucella canis infection in dogs has not traditionally recognized as a major problem. In recent years however, brucellosis resulting from Brucella canis infection has also been reported, suggesting that infections from this species may be increasing. Data concerning the epidemiology of brucellosis resulting from Brucella canis infection is limited. Therefore, the purpose of this study was to assess the diversity among Chinese Brucella canis strains for epidemiological purposes. First, we employed a 16-marker VNTR assay (Brucella MLVA-16) to assess the diversity and epidemiological relationship of 29 Brucella canis isolates from diverse locations throughout China with 38 isolates from other countries. MLVA-16 analysis separated the 67 Brucella canis isolates into 57 genotypes that grouped into five clusters with genetic similarity coefficients ranging from 67.73 to 100%. Moreover, this analysis revealed a new genotype (2-3-9-11-3-1-5-1:118), which was present in two isolates recovered from Guangxi in 1986 and 1987. Second, multiplex PCR and sequencing analysis were used to determine whether the 29 Chinese Brucella canis isolates had the characteristic BMEI1435 gene deletion. Only two isolates had this deletion. Third, amplification of the omp25 gene revealed that 26 isolates from China had a T545C mutation. Collectively, this study reveals that considerable diversity exists among Brucella canis isolates in China and provides resources for studying the genetic variation and microevolution of Brucella. 相似文献
14.
Hasenbrink G Kolacna L Ludwig J Sychrova H Kschischo M Lichtenberg-Fraté H 《Applied microbiology and biotechnology》2007,73(5):1212-1221
Inward rectifying K+ (Kir) channels are a subfamily of the potassium channel superfamily. They mediate potassium influx into the cells, a process
responding to the polarization state, a variety of intracellular messengers and specific auxiliary proteins, thereby they
are involved in important physiological processes such as the pacemaker activity in the heart, insulin release, and potassium
uptake in glial cells. The Saccharomyces cerevisiae mKir2.1 in vitro assay was subjected to a ring test assessment. Compound-associated mKir2.1 modulating effects were detected
by growth determination of functionally complemented S. cerevisiae cells in a 96-well format within 15 h. Dose–response diagrams and EC50 value calculations were determined by parametric model and model-free fits using cubic spline interpolation. These characteristics
were evaluated by statistical methods to determine reproducibility among working groups. Nonparametric bootstrap simulations
of the variability of the data revealed that EC50 values of the mKir2.1 indicator strain were well-matched (81–92 μM), enabling unambiguous quantitative statements about inhibitory
effects and no significant influence of the different laboratory conditions. Limitations of the assay include compounds/samples
that are either insoluble under the conditions of the test or strongly cytotoxic to yeast. Thus, the described test is a sensitive
and reliable tool that can be used in different laboratories and is applicable in drug discovery and development as simple
and reliable prescreening procedure. 相似文献
15.
16.
Longitudinal studies of human leucocyte telomere length often report a percentage of individuals whose telomeres appear to lengthen. However, based on theoretical considerations and empirical data, Steenstrup et al. (Nucleic Acids Research, 2013, vol 41(13): e131) concluded that this lengthening is unlikely to be a real biological phenomenon and is more likely to be an artefact of measurement error. We dispute the logic underlying this claim. We argue that Steenstrup et al.'s analysis is incomplete because it failed to compare predictions derived from assuming a scenario with no true telomere lengthening with alternative scenarios in which true lengthening occurs. To address this deficit, we built a computational model of telomere dynamics that allowed us to compare the predicted percentage of observed telomere length gainers given differing assumptions about measurement error and the true underling dynamics. We modelled a set of scenarios, all assuming measurement error, but both with and without true telomere lengthening. We found a range of scenarios assuming some true telomere lengthening that yielded either similar or better quantitative fits to the empirical data on the percentage of individuals showing apparent telomere lengthening. We conclude that although measurement error contributes to the prevalence of apparent telomere lengthening, Steenstrup et al.'s conclusion was too strong, and current data do not allow us to reject the hypothesis that true telomere lengthening is a real biological phenomenon in epidemiological studies. Our analyses highlight the need for process‐level models in the analysis of telomere dynamics. 相似文献
17.
An important criterion used to detect adaptive evolution in DNA sequence data is ωi > 1, where ωi is the ratio of nonsynonymous to synonymous substitution rates in lineage i. However, the evaluation of multiple ωi within a phylogenetic tree can easily inflate the statistical type I error rate. We developed two rigorous methods of analysis
that avoid this and other potential pitfalls. We applied these methods to four published examples of adaptive evolution. One
case was strongly supported by our reanalysis (abalone sperm lysin), and one was weakly supported (baboon α-globin), but two
examples (primate lysozyme and Antarctic fish β-globin) did not show significant evidence of adaptive evolution. Our first
method is a “bottom-up” hierarchical maximum likelihood approach, which (1) tests for significant heterogeneity in ω across
the phylogeny, (2) locates its source using a sequence of planned comparisons, and (3) tests homogeneous groups of ω for ω
> 1, using a modified level of significance that incorporates the pretesting. The second method is a “top-down” log-linear
analysis based on estimates of nonsynonymous and synonymous substitutions in pairs of lineages. The log-linear test is applied
to pairs of lineages joined at progressively deeper nodes. For each pair, the analysis simultaneously tests for adaptive evolution
(ω > 1), a shift in natural selection (ω1 ≠ω2), and unequal evolution rate (the relative rate test). In both tests, we emphasized that the criterion ω1 ≠ ω2 is an important additional indicator of a phylogenetic shift in the balance between natural selection and genetic drift between
two related lineages.
[Reviewing Editor: Dr. John Huelsenbeck] 相似文献
18.
Svihrova V Hudeckova H Jesenak M Schwarzova K Kostanova Z Ciznar I 《Folia microbiologica》2011,56(3):270-275
Lyme borreliosis (LB) presents as one of the most frequent tick-borne diseases in Europe with more than 85,000 reported cases
every year. The transport of this disease on humans is by tick species of the genus Ixodes. In our work, we aimed to perform a retrospective analysis of the incidence and seasonality of Lyme borreliosis during the
period 1999–2008 in Slovakia. For our analysis, we used all the relevant data about the patients with Lyme borreliosis reported
in the Epidemiological Informative System of Communicable Diseases in Slovakia during the decade of 1999–2008. During the
observed period, there were 7,349 reported cases of LB in Slovakia. Whereas the incidence of early localized infection did
not change during the observed period, there was a significant increase in the incidence of early disseminated infection and
late persistent infection of LB. Seventy per cent of all patients was infected by tick bite. LB was more frequently reported
in females than in males (56.1% vs. 43.9%; p < 0.05), and the most involved age group was the productive age (15–64 years). The incidence of disseminated infection and
persistent infection was rising with increasing age. Regarding the seasonality of LB, we found the highest incidence during
the summer months. Comparing the situation of LB in 1999 and 2008, significant increase in the number of reported cases was
in April and June and from September to November (p < 0.05). Our epidemiological analysis confirmed that Lyme borreliosis requires increased attention due to its increasing
incidence. 相似文献
19.
【背景】禽致病性大肠杆菌(avian pathogenic Escherichia coli,APEC)可引起禽类急性或亚急性感染,在近年新发现的大肠杆菌Ⅲ型分泌系统2 (Escherichia coli type III secretion system 2,ETT2)中,毒力基因yqeH对其致病性的影响尚不明确。【目的】探究yqeH在APEC致病过程中的作用,为后期深入研究ETT2致病机制奠定基础。【方法】利用Red同源重组技术构建yqeH缺失株ΔyqeH及其回复株CΔyqeH,通过运动性、生物被膜形成能力、抗逆性、抗血清杀菌能力等试验分析yqeH对APEC生物学功能的影响,并通过细胞黏附、侵袭试验、致病力测定及荧光定量PCR检测细胞炎性因子转录水平,探究yqeH对APEC感染宿主的影响。【结果】构建了缺失株ΔyqeH和回复株CΔyqeH;生物学特性试验结果表明,与野生株APEC81相比,缺失株ΔyqeH生物被膜形成能力、运动能力降低,对酸、碱、渗透压、氧化休克的耐受力降低,抗血清杀菌能力及致病力显著降低;与野生株APEC81相比,缺失株ΔyqeH对鸡气管黏膜上皮细胞的黏附及侵袭能... 相似文献
20.
One of the critical requirements of data analysis involving large DNA sequences is an effective statistical summarization
of those sequences. In this article DNA sequences have been analyzed based on word frequencies. Our analysis focuses on the
detection of structural signature of a genome reflected in word frequencies and identification of phylogenetic relationships
among different species reflected in the variation of word distributions in their DNA sequences. We have carried out a statistical
study of the complete genome of baker's yeast, of various ribosomal RNA sequences from different prokaryotic and eukaryotic
organisms and of the full genomes of some bacteriophages. Our exploratory analysis amply demonstrates the usefulness of DNA
word frequencies in reducing the dimensionality of large sequences while retaining some of the structural information there
that can have biological significance. Some conceptual issues that arise in course of our investigation have been addressed.
A few interesting problems related to the statistics of DNA words have been pointed out with some indication of their possible
solutions. The work has been partially motivated by the fact that sequence alignment and homology techniques that are quite
popular for comparing and analyzing relatively smaller DNA sequences of nearly equal sizes are not applicable to data consisting
of large sequences with widely varying sizes, which may contain segments with unknown or no biological functions, and consequently
their comparison through functional homology is either impossible or extremely difficult.
Received: 15 October 2000 / Revised version: 8 October 2002
Published online: 28 February 2003
Current address: CF186, Salt lake, Calcutta 700064, India
Research presented here was supported in part by a grant from Indian Statistical Institute.
Key words or phrases: Average linkage clustering – Chernoff's faces – Dendrograms – DNA words – F-ranks of words – F-ratios of words – l
1-distance – Phylogenetic relationships – Rank correlation – Single linkage clustering 相似文献