Analyzing ChIP-chip Data Using Bioconductor

Analyzing ChIP-chip Data Using Bioconducto

Minimum follow-up time required for the estimation of statistical cure of cancer patients: verification using data from 42 cancer sites in the SEER database

BACKGROUND: The present commonly used five-year survival rates are not adequate to represent the statistical cure. In the present study, we established the minimum number of years required for follow-up to estimate statistical cure rate, by using a lognormal distribution of the survival time of those who died of their cancer. We introduced the term, threshold year, the follow-up time for patients dying from the specific cancer covers most of the survival data, leaving less than 2.25% uncovered. This is close enough to cure from that specific cancer. METHODS: Data from the Surveillance, Epidemiology and End Results (SEER) database were tested if the survival times of cancer patients who died of their disease followed the lognormal distribution using a minimum chi-square method. Patients diagnosed from 1973–1992 in the registries of Connecticut and Detroit were chosen so that a maximum of 27 years was allowed for follow-up to 1999. A total of 49 specific organ sites were tested. The parameters of those lognormal distributions were found for each cancer site. The cancer-specific survival rates at the threshold years were compared with the longest available Kaplan-Meier survival estimates. RESULTS: The characteristics of the cancer-specific survival times of cancer patients who died of their disease from 42 cancer sites out of 49 sites were verified to follow different lognormal distributions. The threshold years validated for statistical cure varied for different cancer sites, from 2.6 years for pancreas cancer to 25.2 years for cancer of salivary gland. At the threshold year, the statistical cure rates estimated for 40 cancer sites were found to match the actuarial long-term survival rates estimated by the Kaplan-Meier method within six percentage points. For two cancer sites: breast and thyroid, the threshold years were so long that the cancer-specific survival rates could yet not be obtained because the SEER data do not provide sufficiently long follow-up. CONCLUSION: The present study suggests a certain threshold year is required to wait before the statistical cure rate can be estimated for each cancer site. For some cancers, such as breast and thyroid, the 5- or 10-year survival rates inadequately reflect statistical cure rates, and highlight the need for long-term follow-up of these patients

Large introns in relation to alternative splicing and gene evolution: a case study of Drosophila bruno-3

Background: Alternative splicing (AS) of maturing mRNA can generate structurally and functionally distinct transcripts from the same gene. Recent bioinformatic analyses of available genome databases inferred a positive correlation between intron length and AS. To study the interplay between intron length and AS empirically and in more detail, we analyzed the diversity of alternatively spliced transcripts (ASTs) in the Drosophila RNA-binding Bruno-3 (Bru-3) gene. This gene was known to encode thirteen exons separated by introns of diverse sizes, ranging from 71 to 41,973 nucleotides in D. melanogaster. Although Bru-3's structure is expected to be conducive to AS, only two ASTs of this gene were previously described. Results: Cloning of RT-PCR products of the entire ORF from four species representing three diverged Drosophila lineages provided an evolutionary perspective, high sensitivity, and long-range contiguity of splice choices currently unattainable by high-throughput methods. Consequently, we identified three new exons, a new exon fragment and thirty-three previously unknown ASTs of Bru-3. All exon-skipping events in the gene were mapped to the exons surrounded by introns of at least 800 nucleotides, whereas exons split by introns of less than 250 nucleotides were always spliced contiguously in mRNA. Cases of exon loss and creation during Bru-3 evolution in Drosophila were also localized within large introns. Notably, we identified a true de novo exon gain: exon 8 was created along the lineage of the obscura group from intronic sequence between cryptic splice sites conserved among all Drosophila species surveyed. Exon 8 was included in mature mRNA by the species representing all the major branches of the obscura group. To our knowledge, the origin of exon 8 is the first documented case of exonization of intronic sequence outside vertebrates. Conclusion: We found that large introns can promote AS via exon-skipping and exon turnover during evolution likely due to frequent errors in their removal from maturing mRNA. Large introns could be a reservoir of genetic diversity, because they have a greater number of mutable sites than short introns. Taken together, gene structure can constrain and/or promote gene evolution

Comparing nuclear power trajectories in Germany and the UK: from ‘regimes' to ‘democracies’ in sociotechnical transitions and Discontinuities

This paper focuses on arguably the single most striking contrast in contemporary major energy politics in Europe (and even the developed world as a whole): the starkly differing civil nuclear policies of Germany and the UK. Germany is seeking entirely to phase out nuclear power by 2022. Yet the UK advocates a ‘nuclear renaissance’, promoting the most ambitious new nuclear construction programme in Western Europe.Here,this paper poses a simple yet quite fundamental question: what are the particular divergent conditions most strongly implicated in the contrasting developments in these two countries. With nuclear playing such an iconic role in historical discussions over technological continuity and transformation, answering this may assist in wider understandings of sociotechnical incumbency and discontinuity in the burgeoning field of‘sustainability transitions’. To this end, an ‘abductive’ approach is taken: deploying nine potentially relevant criteria for understanding the different directions pursued in Germany and the UK. Together constituted by 30 parameters spanning literatures related to socio-technical regimes in general as well as nuclear technology in particular, the criteria are divided into those that are ‘internal’ and ‘external’ to the ‘focal regime configuration’ of nuclear power and associated ‘challenger technologies’ like renewables. It is ‘internal’ criteria that are emphasised in conventional sociotechnical regime theory, with ‘external’ criteria relatively less well explored. Asking under each criterion whether attempted discontinuation of nuclear power would be more likely in Germany or the UK, a clear picture emerges. ‘Internal’ criteria suggest attempted nuclear discontinuation should be more likely in the UK than in Germany– the reverse of what is occurring. ‘External’ criteria are more aligned with observed dynamics –especially those relating to military nuclear commitments and broader ‘qualities of democracy’. Despite many differences of framing concerning exactly what constitutes ‘democracy’, a rich political science literature on this point is unanimous in characterising Germany more positively than the UK. Although based only on a single case,a potentially important question is nonetheless raised as to whether sociotechnical regime theory might usefully give greater attention to the general importance of various aspects of democracy in constituting conditions for significant technological discontinuities and transformations. If so, the policy implications are significant. A number of important areas are identified for future research, including the roles of diverse understandings and specific aspects of democracy and the particular relevance of military nuclear commitments– whose under-discussion in civil nuclear policy literatures raises its own questions of democratic accountability

Global Identification and Characterization of Transcriptionally Active Regions in the Rice Genome

Genome tiling microarray studies have consistently documented rich transcriptional activity beyond the annotated genes. However, systematic characterization and transcriptional profiling of the putative novel transcripts on the genome scale are still lacking. We report here the identification of 25,352 and 27,744 transcriptionally active regions (TARs) not encoded by annotated exons in the rice (Oryza. sativa) subspecies japonica and indica, respectively. The non-exonic TARs account for approximately two thirds of the total TARs detected by tiling arrays and represent transcripts likely conserved between japonica and indica. Transcription of 21,018 (83%) japonica non-exonic TARs was verified through expression profiling in 10 tissue types using a re-array in which annotated genes and TARs were each represented by five independent probes. Subsequent analyses indicate that about 80% of the japonica TARs that were not assigned to annotated exons can be assigned to various putatively functional or structural elements of the rice genome, including splice variants, uncharacterized portions of incompletely annotated genes, antisense transcripts, duplicated gene fragments, and potential non-coding RNAs. These results provide a systematic characterization of non-exonic transcripts in rice and thus expand the current view of the complexity and dynamics of the rice transcriptome

Inflammatory Genital Infections Mitigate a Severe Genetic Bottleneck in Heterosexual Transmission of Subtype A and C HIV-1

The HIV-1 epidemic in sub-Saharan Africa is driven largely by heterosexual transmission of non-subtype B viruses, of which subtypes C and A are predominant. Previous studies of subtype B and subtype C transmission pairs have suggested that a single variant from the chronically infected partner can establish infection in their newly infected partner. However, in subtype A infected individuals from a sex worker cohort and subtype B individuals from STD clinics, infection was frequently established by multiple variants. This study examined over 1750 single-genome amplified viral sequences derived from epidemiologically linked subtype C and subtype A transmission pairs very early after infection. In 90% (18/20) of the pairs, HIV-1 infection is initiated by a single viral variant that is derived from the quasispecies of the transmitting partner. In addition, the virus initiating infection in individuals who were infected by someone other than their spouse was characterized to determine if genital infections mitigated the severe genetic bottleneck observed in a majority of epidemiologically linked heterosexual HIV-1 transmission events. In nearly 50% (3/7) of individuals infected by someone other than their spouse, multiple genetic variants from a single individual established infection. A statistically significant association was observed between infection by multiple genetic variants and an inflammatory genital infection in the newly infected individual. Thus, in the vast majority of HIV-1 transmission events in cohabiting heterosexual couples, a single genetic variant establishes infection. Nevertheless, this severe genetic bottleneck can be mitigated by the presence of inflammatory genital infections in the at risk partner, suggesting that this restriction on genetic diversity is imposed in large part by the mucosal barrier

Lung epithelial stem cells and their niches : Fgf10 takes center stage

Throughout life adult animals crucially depend on stem cell populations to maintain and repair their tissues to ensure life-long organ function. Stem cells are characterized by their capacity to extensively self-renew and give rise to one or more differentiated cell types. These powerful stem cell properties are key to meet the changing demand for tissue replacement during normal lung homeostasis and regeneration after lung injury. Great strides have been made over the last few years to identify and characterize lung epithelial stem cells as well as their lineage relationships. Unfortunately, knowledge on what regulates the behavior and fate specification of lung epithelial stem cells is still limited, but involves communication with their microenvironment or niche, a local tissue environment that hosts and influences the behaviors or characteristics of stem cells and that comprises other cell types and extracellular matrix. As such, an intimate and dynamic epithelial-mesenchymal cross-talk, which is also essential during lung development, is required for normal homeostasis and to mount an appropriate regenerative response after lung injury. Fibroblast growth factor 10 (Fgf10) signaling in particular seems to be a well-conserved signaling pathway governing epithelial-mesenchymal interactions during lung development as well as between different adult lung epithelial stem cells and their niches. On the other hand, disruption of these reciprocal interactions leads to a dysfunctional epithelial stem cell-niche unit, which may culminate in chronic lung diseases such as chronic obstructive pulmonary disease (COPD), chronic asthma and idiopathic pulmonary fibrosis (IPF)

Disseminated Coccidioidomycosis: Cutaneous, Soft Tissue, Osseous, and “Shotgun Intraparenchymal” Brain Disease

Coccidioidomycosis is a disease found in the southwestern United States and caused by inhalation of arthroconidia of Coccidioides immitis and posadasii. Although the disease is most commonly asymptomatic or respiratory, it has a propensity to disseminate to any tissue in the body with the most common being skin, bone, joints, and central nervous system. This case demonstrates the dissemination of coccidioidomycosis to several foci along with a rare form of parenchymal dissemination with an unusual neuroradiological finding