Computational and Biological Analogies for Understanding Fine-Tuned Parameters in Physics

In this philosophical paper, we explore computational and biological analogies to address the fine-tuning problem in cosmology. We first clarify what it means for physical constants or initial conditions to be fine-tuned. We review important distinctions such as the dimensionless and dimensional physical constants, and the classification of constants proposed by Levy-Leblond. Then we explore how two great analogies, computational and biological, can give new insights into our problem. This paper includes a preliminary study to examine the two analogies. Importantly, analogies are both useful and fundamental cognitive tools, but can also be misused or misinterpreted. The idea that our universe might be modelled as a computational entity is analysed, and we discuss the distinction between physical laws and initial conditions using algorithmic information theory. Smolin introduced the theory of "Cosmological Natural Selection" with a biological analogy in mind. We examine an extension of this analogy involving intelligent life. We discuss if and how this extension could be legitimated. Keywords: origin of the universe, fine-tuning, physical constants, initial conditions, computational universe, biological universe, role of intelligent life, cosmological natural selection, cosmological artificial selection, artificial cosmogenesis.Comment: 25 pages, Foundations of Science, in pres

Efficient error correction for next-generation sequencing of viral amplicons

<p>Abstract</p> <p>Background</p> <p>Next-generation sequencing allows the analysis of an unprecedented number of viral sequence variants from infected patients, presenting a novel opportunity for understanding virus evolution, drug resistance and immune escape. However, sequencing in bulk is error prone. Thus, the generated data require error identification and correction. Most error-correction methods to date are not optimized for amplicon analysis and assume that the error rate is randomly distributed. Recent quality assessment of amplicon sequences obtained using 454-sequencing showed that the error rate is strongly linked to the presence and size of homopolymers, position in the sequence and length of the amplicon. All these parameters are strongly sequence specific and should be incorporated into the calibration of error-correction algorithms designed for amplicon sequencing.</p> <p>Results</p> <p>In this paper, we present two new efficient error correction algorithms optimized for viral amplicons: (i) k-mer-based error correction (KEC) and (ii) empirical frequency threshold (ET). Both were compared to a previously published clustering algorithm (SHORAH), in order to evaluate their relative performance on 24 experimental datasets obtained by 454-sequencing of amplicons with known sequences. All three algorithms show similar accuracy in finding true haplotypes. However, KEC and ET were significantly more efficient than SHORAH in removing false haplotypes and estimating the frequency of true ones.</p> <p>Conclusions</p> <p>Both algorithms, KEC and ET, are highly suitable for rapid recovery of error-free haplotypes obtained by 454-sequencing of amplicons from heterogeneous viruses.</p> <p>The implementations of the algorithms and data sets used for their testing are available at: <url>http://alan.cs.gsu.edu/NGS/?q=content/pyrosequencing-error-correction-algorithm</url></p

Simple tools for assembling and searching high-density picolitre pyrophosphate sequence data

<p>Abstract</p> <p>Background</p> <p>The advent of pyrophosphate sequencing makes large volumes of sequencing data available at a lower cost than previously possible. However, the short read lengths are difficult to assemble and the large dataset is difficult to handle. During the sequencing of a virus from the tsetse fly, <it>Glossina pallidipes</it>, we found the need for tools to search quickly a set of reads for near exact text matches.</p> <p>Methods</p> <p>A set of tools is provided to search a large data set of pyrophosphate sequence reads under a "live" CD version of Linux on a standard PC that can be used by anyone without prior knowledge of Linux and without having to install a Linux setup on the computer. The tools permit short lengths of <it>de novo </it>assembly, checking of existing assembled sequences, selection and display of reads from the data set and gathering counts of sequences in the reads.</p> <p>Results</p> <p>Demonstrations are given of the use of the tools to help with checking an assembly against the fragment data set; investigating homopolymer lengths, repeat regions and polymorphisms; and resolving inserted bases caused by incomplete chain extension.</p> <p>Conclusion</p> <p>The additional information contained in a pyrophosphate sequencing data set beyond a basic assembly is difficult to access due to a lack of tools. The set of simple tools presented here would allow anyone with basic computer skills and a standard PC to access this information.</p

Chromosomal-level assembly of the Asian Seabass genome using long sequence reads and multi-layered scaffolding

We report here the ~670 Mb genome assembly of the Asian seabass (Lates calcarifer), a tropical marine teleost. We used long-read sequencing augmented by transcriptomics, optical and genetic mapping along with shared synteny from closely related fish species to derive a chromosome-level assembly with a contig N50 size over 1 Mb and scaffold N50 size over 25 Mb that span ~90% of the genome. The population structure of L. calcarifer species complex was analyzed by re-sequencing 61 individuals representing various regions across the species' native range. SNP analyses identified high levels of genetic diversity and confirmed earlier indications of a population stratification comprising three clades with signs of admixture apparent in the South-East Asian population. The quality of the Asian seabass genome assembly far exceeds that of any other fish species, and will serve as a new standard for fish genomics

AIDS-Related Tuberculosis in Rio de Janeiro, Brazil

BACKGROUND: We studied the incidence of tuberculosis, AIDS, AIDS deaths and AIDS-TB co-infection at the population level in Rio de Janeiro, Brazil where universal and free access to combination antiretroviral therapy has been available since 1997. METHODOLOGY/PRINCIPAL FINDINGS: This was a retrospective surveillance database match of Rio de Janeiro databases from 1995-2004. Proportions of tuberculosis occurring within 30 days and between 30 days and 1 year after AIDS diagnosis were determined. Generalized additive models fitted with cubic splines with appropriate estimating methods were used to describe rates and proportions over time. Overall, 90,806 tuberculosis cases and 16,891 AIDS cases were reported; 3,125 tuberculosis cases within 1 year of AIDS diagnosis were detected. Tuberculosis notification rates decreased after 1997 from a fitted rate (fR per 100,000) of 166.5 to 138.8 in 2004. AIDS incidence rates increased 26% between 1995 and 1998 (30.7 to 38.7) followed by a 33.3% decrease to 25.8 in 2004. AIDS mortality rates decreased dramatically after antiretroviral therapy was introduced between 1995 (27.5) and 1999 (13.4). The fitted proportion (fP) of patients with tuberculosis diagnosed within one year of AIDS decreased from 1995 (24.4%) to 1998 (15.2%), remaining stable since. Seventy-five percent of tuberculosis diagnoses after an AIDS diagnosis occurred within 30 days of AIDS diagnosis. CONCLUSIONS/SIGNIFICANCE: Our results suggest that while combination ART should be considered an essential component of the response to the HIV and HIV/tuberculosis epidemics, it may not be sufficient alone to prevent progression from latent TB to active disease among HIV-infected populations. When tuberculosis is diagnosed prior to or at the same time as AIDS and ART has not yet been initiated, then ART is ineffective as a tuberculosis prevention strategy for these patients. Earlier HIV/AIDS diagnosis and ART initiation may reduce TB incidence in HIV/AIDS patients. More specific interventions will be required if HIV-related tuberculosis incidence is to continue to decline

500 ml of blood loss does not decrease non-invasive tissue oxygen saturation (StO2) as measured by near infrared spectroscopy - A hypothesis generating pilot study in healthy adult women

BACKGROUND: The goal when resuscitating trauma patients is to achieve adequate tissue perfusion. One parameter of tissue perfusion is tissue oxygen saturation (StO2), as measured by near infrared spectroscopy. Using a commercially available device, we investigated whether clinically relevant blood loss of 500 ml in healthy volunteers can be detected by changes in StO2 after a standardized ischemic event. METHODS: We performed occlusion of the brachial artery for 3 minutes in 20 healthy female blood donors before and after blood donation. StO2 and total oxygenated tissue hemoglobin (O2Hb) were measured continuously at the thenar eminence. 10 healthy volunteers were assessed in the same way, to examine whether repeated vascular occlusion without blood donation exhibits time dependent effects. RESULTS: Blood donation caused a substantial decrease in systolic blood pressure, but did not affect resting StO2 and O2Hb values. No changes were measured in the blood donor group in the reaction to the vascular occlusion test, but in the control group there was an increase in the O2Hb rate of recovery during the reperfusion phase. CONCLUSION: StO2 measured at the thenar eminence seems to be insensitive to blood loss of 500 ml in this setting. Probably blood loss greater than this might lead to detectable changes guiding the treating physician. The exact cut off for detectable changes and the time effect on repeated vascular occlusion tests should be explored further. Until now no such data exist

Multidrug-resistant Mycobacterium tuberculosis in HIV-Infected Persons, Peru

During 1999 to 2000, we identified HIV-infected persons with new episodes of tuberculosis (TB) at 10 hospitals in Lima-Peru and a random sample of other Lima residents with TB. Multidrug-resistant (MDR)-TB was documented in 35 (43%) of 81 HIV-positive patients and 38 (3.9%)of 965 patients who were HIV-negative or of unknown HIV status (p < 0.001). HIV-positive patients with MDR-TB were concentrated at three hospitals that treat the greatest numbers of HIV-infected persons with TB. Of patients with TB, those with HIV infection differed from those without known HIV infection in having more frequent prior exposure to clinical services and more frequent previous TB therapy or prophylaxis. However, MDR-TB in HIV-infected patients was not associated with previous TB therapy or prophylaxis. MDR-TB is an ongoing problem in HIV-infected persons receiving care in public hospitals in Lima and Callao; they represent sentinel cases for a potentially larger epidemic of nosocomial MDR-TB

Corrigendum: An ethnically relevant consensus Korean reference genome is a step towards personal reference genomes.

This corrects the article DOI: 10.1038/ncomms13637

Identification of polymorphic inversions from genotypes

Background: Polymorphic inversions are a source of genetic variability with a direct impact on recombination frequencies. Given the difficulty of their experimental study, computational methods have been developed to infer their existence in a large number of individuals using genome-wide data of nucleotide variation. Methods based on haplotype tagging of known inversions attempt to classify individuals as having a normal or inverted allele. Other methods that measure differences between linkage disequilibrium attempt to identify regions with inversions but unable to classify subjects accurately, an essential requirement for association studies. Results: We present a novel method to both identify polymorphic inversions from genome-wide genotype data and classify individuals as containing a normal or inverted allele. Our method, a generalization of a published method for haplotype data [1], utilizes linkage between groups of SNPs to partition a set of individuals into normal and inverted subpopulations. We employ a sliding window scan to identify regions likely to have an inversion, and accumulation of evidence from neighboring SNPs is used to accurately determine the inversion status of each subject. Further, our approach detects inversions directly from genotype data, thus increasing its usability to current genome-wide association studies (GWAS). Conclusions: We demonstrate the accuracy of our method to detect inversions and classify individuals on principled-simulated genotypes, produced by the evolution of an inversion event within a coalescent model [2]. We applied our method to real genotype data from HapMap Phase III to characterize the inversion status of two known inversions within the regions 17q21 and 8p23 across 1184 individuals. Finally, we scan the full genomes of the European Origin (CEU) and Yoruba (YRI) HapMap samples. We find population-based evidence for 9 out of 15 well-established autosomic inversions, and for 52 regions previously predicted by independent experimental methods in ten (9+1) individuals [3,4]. We provide efficient implementations of both genotype and haplotype methods as a unified R package inveRsion