Fractal-like Distributions over the Rational Numbers in High-throughput Biological and Clinical Data

Recent developments in extracting and processing biological and clinical data are allowing quantitative approaches to studying living systems. High-throughput sequencing, expression profiles, proteomics, and electronic health records are some examples of such technologies. Extracting meaningful information from those technologies requires careful analysis of the large volumes of data they produce. In this note, we present a set of distributions that commonly appear in the analysis of such data. These distributions present some interesting features: they are discontinuous in the rational numbers, but continuous in the irrational numbers, and possess a certain self-similar (fractal-like) structure. The first set of examples which we present here are drawn from a high-throughput sequencing experiment. Here, the self-similar distributions appear as part of the evaluation of the error rate of the sequencing technology and the identification of tumorogenic genomic alterations. The other examples are obtained from risk factor evaluation and analysis of relative disease prevalence and co-mordbidity as these appear in electronic clinical data. The distributions are also relevant to identification of subclonal populations in tumors and the study of the evolution of infectious diseases, and more precisely the study of quasi-species and intrahost diversity of viral populations

T-cell cytotoxicity in the absence of viral protein synthesis in target cells

CYTOTOXIC T cells lyse only those virus infected target cells in vitro which express, in addition to the viral antigen(s), those K or D region products of the major histocompati-bility complex (MHC) which were present during anti-viral sensitisation in vivo. This 'associative recogniton' by cytotoxic T cells could reflect the interaction of two T-cell receptors with specificity for target K or D gene products and independently for the viral antigen, or one receptor with specificity for virally altered K or D region products (see ref. 1 and refs therein). There are various ways that the MHC antigens could be altered, including 'modification from within', where the virus modifies host protein synthesis by interfering with transcription2, translation or post-translational glycosylation; or 'modification from without' where enzymic or chemical alteration of cell membrane proteins are induced by virus activity at the cell surface. In this report we show that inactivated Sendai virus or isolated Sendai virus envelopes can serve to modify a cell and make it a specific target for Sendai-immune T-cell killing, thus excluding the possibility of 'modification from within' in this system

Limitations of Majority Agreement in Crowdsourced Image Interpretation

Crowdsourcing can efficiently complete tasks that are difficult to automate, but the quality of crowdsourced data is tricky to evaluate. Algorithms to grade volunteer work often assume that all tasks are similarly difficult, an assumption that is frequently false. We use a cropland identification game with over 2,600 participants and 165,000 unique tasks to investigate how best to evaluate the difficulty of crowdsourced tasks and to what extent this is possible based on volunteer responses alone. Inter-volunteer agreement exceeded 90% for about 80% of the images and was negatively correlated with volunteer-expressed uncertainty about image classification. A total of 343 relatively difficult images were independently classified as cropland, non-cropland or impossible by two experts. The experts disagreed weakly (one said impossible while the other rated as cropland or non-cropland) on 27% of the images, but disagreed strongly (cropland vs. non-cropland) on only 7%. Inter-volunteer disagreement increased significantly with inter-expert disagreement. While volunteers agreed with expert classifications for most images, over 20% would have been mis-categorized if only the volunteers’ majority vote was used. We end with a series of recommendations for managing the challenges posed by heterogeneous tasks in crowdsourcing campaigns

Two-temperature LATE-PCR endpoint genotyping

BACKGROUND: In conventional PCR, total amplicon yield becomes independent of starting template number as amplification reaches plateau and varies significantly among replicate reactions. This paper describes a strategy for reconfiguring PCR so that the signal intensity of a single fluorescent detection probe after PCR thermal cycling reflects genomic composition. The resulting method corrects for product yield variations among replicate amplification reactions, permits resolution of homozygous and heterozygous genotypes based on endpoint fluorescence signal intensities, and readily identifies imbalanced allele ratios equivalent to those arising from gene/chromosomal duplications. Furthermore, the use of only a single colored probe for genotyping enhances the multiplex detection capacity of the assay. RESULTS: Two-Temperature LATE-PCR endpoint genotyping combines Linear-After-The-Exponential (LATE)-PCR (an advanced form of asymmetric PCR that efficiently generates single-stranded DNA) and mismatch-tolerant probes capable of detecting allele-specific targets at high temperature and total single-stranded amplicons at a lower temperature in the same reaction. The method is demonstrated here for genotyping single-nucleotide alleles of the human HEXA gene responsible for Tay-Sachs disease and for genotyping SNP alleles near the human p53 tumor suppressor gene. In each case, the final probe signals were normalized against total single-stranded DNA generated in the same reaction. Normalization reduces the coefficient of variation among replicates from 17.22% to as little as 2.78% and permits endpoint genotyping with >99.7% accuracy. These assays are robust because they are consistent over a wide range of input DNA concentrations and give the same results regardless of how many cycles of linear amplification have elapsed. The method is also sufficiently powerful to distinguish between samples with a 1:1 ratio of two alleles from samples comprised of 2:1 and 1:2 ratios of the same alleles. CONCLUSION: SNP genotyping via Two-Temperature LATE-PCR takes place in a homogeneous closed-tube format and uses a single hybridization probe per SNP site. These assays are convenient, rely on endpoint analysis, improve the options for construction of multiplex assays, and are suitable for SNP genotyping, mutation scanning, and detection of DNA duplication or deletions

LACO-Wiki: A New Online Land Cover Validation Tool Demonstrated Using GlobeLand30 for Kenya

Accuracy assessment, also referred to as validation, is a key process in the workflow of developing a land cover map. To make this process open and transparent, we have developed a new online tool called LACO-Wiki, which encapsulates this process into a set of four simple steps including uploading a land cover map, creating a sample from the map, interpreting the sample with very high resolution satellite imagery and generating a report with accuracy measures. The aim of this paper is to present the main features of this new tool followed by an example of how it can be used for accuracy assessment of a land cover map. For the purpose of illustration, we have chosen GlobeLand30 for Kenya. Two different samples were interpreted by three individuals: one sample was provided by the GlobeLand30 team as part of their international efforts in validating GlobeLand30 with GEO (Group on Earth Observation) member states while a second sample was generated using LACO-Wiki. Using satellite imagery from Google Maps, Bing and Google Earth, the results show overall accuracies between 53% to 61%, which is lower than the global accuracy assessment of GlobeLand30 but may be reasonable given the complex landscapes found in Kenya. Statistical models were then fit to the data to determine what factors affect the agreement between the three interpreters such as the land cover class, the presence of very high resolution satellite imagery and the age of the image in relation to the baseline year for GlobeLand30 (2010). The results showed that all factors had a significant effect on the agreement

Conformity and tradition are more important than environmental values in constraining resource overharvest

We present the results of a hybrid research design that borrows from both experimental techniques-experimental games-and observational techniques-surveys-to examine the relationships between basic human values and exposure to natural ecosystems, on the one hand, and collective action for resource governance, on the other. We initially hypothesize that more frequent exposure to forests, and more pro-environmental values will be associated with more conservation action. However, we find that other values-tradition and conformity-are more important than pro-environmental values or exposure to nature. Our results imply that resource governance is likely to be more successful where resource users hold values that facilitate cooperation, not necessarily strong pro-environmental values

Lateralization of infant holding by mothers: a longitudinal evaluation of variations over the first 12 weeks

The maternal preference to hold infants on the left rather than right side of the body was examined longitudinally, with attention to four explanations: maternal monitoring of infant state, maternal handedness, infant proximity to the mother’s heartbeat, and preferred infant head position. The side and site of holding were measured over the first twelve weeks of the lives of 24 infants. Information about group and individual consistency in holding side allowed novel evaluation of the theories. A strong bias to hold on the left dropped below significance when the infants were aged twelve weeks and was limited to specific holding positions. Findings were generally consistent with the monitoring hypothesis, and little support was found for the three alternative explanations

Role of spinon and spinon singlet pair excitations on phase transitions in d−waved-wave superconductors

We examine the roles of massless Dirac spinon and spin singlet pair excitations on the phase transition in $d-wave$ superconductors. Although the massless spinon excitations in the presence of the spin singlet pair excitations do not alter the nature of the phase transition at $T = 0$, that is, the XY universality class, they are seen to induce an additional attractive interaction potential between vortices, further stabilizing vortex-antivortex pairs at low temperature for lightly doped high $T_c$ samples.Comment: 5 pages, 1 figur

Multiple reassortment events in the evolutionary history of H1N1 influenza A virus since 1918

The H1N1 subtype of influenza A virus has caused substantial morbidity and mortality in humans, first documented in the global pandemic of 1918 and continuing to the present day. Despite this disease burden, the evolutionary history of the A/H1N1 virus is not well understood, particularly whether there is a virological basis for several notable epidemics of unusual severity in the 1940s and 1950s. Using a data set of 71 representative complete genome sequences sampled between 1918 and 2006, we show that segmental reassortment has played an important role in the genomic evolution of A/H1N1 since 1918. Specifically, we demonstrate that an A/H1N1 isolate from the 1947 epidemic acquired novel PB2 and HA genes through intra-subtype reassortment, which may explain the abrupt antigenic evolution of this virus. Similarly, the 1951 influenza epidemic may also have been associated with reassortant A/H1N1 viruses. Intra-subtype reassortment therefore appears to be a more important process in the evolution and epidemiology of H1N1 influenza A virus than previously realized