Rethinking the Kolmogorov-Smirnov test of Goodness of fit in a compositional way

The Kolmogorov Smirnov test (KS) is a well known test used to asses how a set of observations is significantly different from the probability model specified under the null hypothesis. The KS test statistic quantifies the distance between the empirical distribution function and the hypothetical one. The modification introduced in Monti et al. (2017) consists of computing the mentioned distances as Aitchison distances. In this contribution, we suggest a further modification of the latter test and investigate, by simulation, the asymptotic distribution of the proposed test statistic, checking the appropriateness of a Generalized Extreme Value (GEV) Distribution. The properties of the asymptotic distribution are studied via Monte Carlo simulations.Peer ReviewedPostprint (author's final draft

Comparison of X-ray dose-response curves obtained by chromosome painting using conventional and PAINT nomenclatures

Altres ajuts: Consejo Español de Seguridad Nuclear (exp. 246/96)Purpose: The compare the suitability of PAINT and conventional nomenclature systems for the construction of chromosome aberration dose- effect curves for X-rays using FISH techniques, and to compare these curves with those based on solid-stained dicentrics analysed in first division metaphases by the FPG technique. Materials and methods: Blood samples were irradiated at 0.1, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4 and 5 Gy 180 kV X-rays. FISH painting was performed using probes for chromosomes 1, 4 and 11 in combination with a pan-centromeric probe. Results: Translocations showed a higher background frequency than dicentrics. This influences the ratio of translocations:dicentrics at the lower doses and the uncertainties of dose- effect curves for translocations. The dose-effect curves for dicentrics obtained by FISH and solid stain were in close agreement. Conclusion: For short-term biological dosimetry purposes by FISH, the use of dic(BA) (PAINT nomenclature) or total dicentrics (conventional nomenclature) should give similar dose estimates. For dose reconstruction, the use of total or complete translocations result in similar uncertainties

Estimating the evidence of selection and the reliability of inference in unigenic evolution

<p>Abstract</p> <p>Background</p> <p>Unigenic evolution is a large-scale mutagenesis experiment used to identify residues that are potentially important for protein function. Both currently-used methods for the analysis of unigenic evolution data analyze 'windows' of contiguous sites, a strategy that increases statistical power but incorrectly assumes that functionally-critical sites are contiguous. In addition, both methods require the questionable assumption of asymptotically-large sample size due to the presumption of approximate normality.</p> <p>Results</p> <p>We develop a novel approach, termed the Evidence of Selection (EoS), removing the assumption that functionally important sites are adjacent in sequence and and explicitly modelling the effects of limited sample-size. Precise statistical derivations show that the EoS score can be easily interpreted as an expected log-odds-ratio between two competing hypotheses, namely, the hypothetical presence or absence of functional selection for a given site. Using the EoS score, we then develop selection criteria by which functionally-important yet non-adjacent sites can be identified. An approximate power analysis is also developed to estimate the reliability of inference given the data. We validate and demonstrate the the practical utility of our method by analysis of the homing endonuclease <monospace>I-Bmol</monospace>, comparing our predictions with the results of existing methods.</p> <p>Conclusions</p> <p>Our method is able to assess both the evidence of selection at individual amino acid sites and estimate the reliability of those inferences. Experimental validation with <monospace>I-Bmol</monospace> proves its utility to identify functionally-important residues of poorly characterized proteins, demonstrating increased sensitivity over previous methods without loss of specificity. With the ability to guide the selection of precise experimental mutagenesis conditions, our method helps make unigenic analysis a more broadly applicable technique with which to probe protein function.</p> <p>Availability</p> <p>Software to compute, plot, and summarize EoS data is available as an open-source package called 'unigenic' for the 'R' programming language at <url>http://www.fernandes.org/txp/article/13/an-analytical-framework-for-unigenic-evolution</url>.</p

High-risk sex behavior and HIV prevalence among gay and bisexual men in the community of Madrid

BACKGROUND: To analyze high-risk sexual behavior as regards HIV, the use of preventive measures and the patient-reported prevalence of HIV infections among males belonging to one of the leading homosexual associations in the Region of Madrid. METHODS: Cross-sectional study conducted in 1997-1998 by way of mailed anonymous questionnaires. An analysis is made of the sociodemographic characteristics, how often condoms are used for different types of sexual intercourse with regular or casual partners, patient-reported prevalence of HIV and other related aspects. RESULTS: 157 questionnaires were returned by gay/bisexual males. These subjects averaged 32 years of age, 85% having a high school or college education, over the past 3 months, 56% had had intercourse with more than one man; 70.6% practiced insertive anal intercourse with a regular partner and 57.4% with casual partners, solely 32.5% and 61.1% of whom always used a condom. 69.7% had receptive anal intercourse with a regular partner and 39.4% with casual partners, 35.5% and 78.4% of whom respectively always used a condom. 86.6% had oral-genital intercourse, less than 10% having always used a condom. 137 were aware of their serological condition, and 15.2% were HIV positive. 10% had had some STD at some point during the previous year. CONCLUSIONS: A major percentage of those surveyed were involved in high-risk practices (several partners and unprotected high-risk sexual intercourse) which, in conjunction with the major prevalence of infection, can be said to be the same as a major seroconversion rate. ra la infección por VIH, el uso de medidas de preven- ción y la prevalencia autoinformada de infección por VIH en varones de una de las principales asociaciones de homo- sexuales de la Comunidad de Madrid. Métodos: Estudio tmnsversal realizado durante 1997- 1998. mediante un cuestionario anónimo remitido por correo. Se analizan las caructerísticas sociodemogrificas, la frecuen- cia de uso del preservativo en las distintas prklicas sexuales con la pareja estable y con las ocasionales. la prevalen& au- toinformada de VIH y otros aspectos relacionados. Resultados: Se obtuvieron 157 cuestionarios de varones homosexuales y bisexuales. Su edad media fue de 32 aiíos y el 85% tenía estudios medios o superiores. En los últimos 3 me- ses: el 56% tuvo relaciones con ~xí.s de un hombre; el 70.6% practicó la penetración anal insertiva con pareja estable y el 57,3% con conpactos ocasionales, de los que sólo el 33,510 y el 61,1% respectivamente utilizaron siempre el preservativo. La penetración anal receptiva la realizaron el 09.7% con pareja estable y el 39,4% con contactos ocasionales, utilizando siem- pre el preservativo el 355% y el 78,4% respectivamente. El 86.6% tuvieron relaciones oro-genitales y menos del 10% uti- lizaron siempre el preservativo. 137 hombres conocím su es- tado serológico y el 15,2% resultó VIH positivo. El 102% padeció alguna ETS durante el último aio. Conclusiones: Un importante porcentaje de entrevis- tndos mantiene prkticas de riesgo (varias parejas y relacio- nes sexuales de alto riesgo sin protección) que, asociado a una prevalencia de infección elevada, puede traducirse en unti importante tasa de seroconversión.Proyecto financiado por el Fondo de Investigación sanitaria ()

Impact of index hopping and bias towards the reference allele on accuracy of genotype calls from low-coverage sequencing

Abstract Background Inherent sources of error and bias that affect the quality of sequence data include index hopping and bias towards the reference allele. The impact of these artefacts is likely greater for low-coverage data than for high-coverage data because low-coverage data has scant information and many standard tools for processing sequence data were designed for high-coverage data. With the proliferation of cost-effective low-coverage sequencing, there is a need to understand the impact of these errors and bias on resulting genotype calls from low-coverage sequencing. Results We used a dataset of 26 pigs sequenced both at 2× with multiplexing and at 30× without multiplexing to show that index hopping and bias towards the reference allele due to alignment had little impact on genotype calls. However, pruning of alternative haplotypes supported by a number of reads below a predefined threshold, which is a default and desired step of some variant callers for removing potential sequencing errors in high-coverage data, introduced an unexpected bias towards the reference allele when applied to low-coverage sequence data. This bias reduced best-guess genotype concordance of low-coverage sequence data by 19.0 absolute percentage points. Conclusions We propose a simple pipeline to correct the preferential bias towards the reference allele that can occur during variant discovery and we recommend that users of low-coverage sequence data be wary of unexpected biases that may be produced by bioinformatic tools that were designed for high-coverage sequence data

Prospective assessment of Y-chromosome microdeletions and reproductive outcomes among infertile couples of Japanese and African origin

BACKGROUND: To compare the frequency of Y-chromosome microdeletions in Japanese and African azoospermic and oligozoospermic men and describe embryo characteristics and reproductive outcome following in vitro fertilization (IVF) with intracytoplasmic sperm injection (ICSI). METHODS: Our study was performed prospectively at two centers, a private IVF clinic and a university hospital. Japanese and African (Tanzanian) men with nonobstructive azoospermia (NOA) and oligozoospermia (concentration < 5 × 10(6 )/ml) were evaluated for Y-chromosome microdeletions (n = 162). Of the 47 men with NOA, 26 were Japanese and 21 were Africans. Of the 115 men with oligozoospermia, 87 were Japanese and 28 were Africans. Reproductive outcomes of patients with Y-chromosome microdeletions were then compared with those of 19 IVF+ICSI cycles performed on couples with Y-chromosome intact males/tubal factor infertility which served as a control group. RESULTS: Seven azoospermic and oligozoospermic patients had Y-chromosome deletions; the total number of deletions in the AZFc region was five. There was only one deletion in the AZFa region and one complete deletion involving all three regions (AZFa, b, and c) within AZF. In our study population, microdeletion frequency among Japanese men was 6.2% (95% CI, 4.25% – 14.45%), whereas no deletions were identified in the African group (95% CI, 0.0% – 7.27%). The difference between the two groups was not statistically significant, however. Embryos derived from ICSI utilizing sperm with Y-chromosome microdeletion showed reduced rates of fertilization, blastocyst development, implantation, and pregnancy compared to the Y-chromosome intact group, although these observed differences were not statistically significant. CONCLUSION: The observed frequency of Y-chromosome microdeletion was 6.2% among Japanese azoospermic and oligozoospermic males; no microdeletions were identified among our African study patients. In this population of couples undergoing IVF+ICSI, there was no statistically significant difference in embryo characteristics or pregnancy outcome between patients with Y-chromosome microdeletion and those with an intact Y-chromosome

Modeling Intrinsically Disordered Proteins with Bayesian Statistics

The characterization of intrinsically disordered proteins is challenging because accurate models of these systems require a description of both their thermally accessible conformers and the associated relative stabilities or weights. These structures and weights are typically chosen such that calculated ensemble averages agree with some set of prespecified experimental measurements; however, the large number of degrees of freedom in these systems typically leads to multiple conformational ensembles that are degenerate with respect to any given set of experimental observables. In this work we demonstrate that estimates of the relative stabilities of conformers within an ensemble are often incorrect when one does not account for the underlying uncertainty in the estimates themselves. Therefore, we present a method for modeling the conformational properties of disordered proteins that estimates the uncertainty in the weights of each conformer. The Bayesian weighting (BW) formalism incorporates information from both experimental data and theoretical predictions to calculate a probability density over all possible ways of weighting the conformers in the ensemble. This probability density is then used to estimate the values of the weights. A unique and powerful feature of the approach is that it provides a built-in error measure that allows one to assess the accuracy of the ensemble. We validate the approach using reference ensembles constructed from the five-residue peptide met-enkephalin and then apply the BW method to construct an ensemble of the K18 isoform of the tau protein. Using this ensemble, we indentify a specific pattern of long-range contacts in K18 that correlates with the known aggregation properties of the sequence.National Institutes of Health (U.S.) (NIH Grant 5R21NS063185-02