Teaching data science and cloud computing in low and middle income countries

Large, publicly available data sets present a challenge and an opportunity for researchers based in Low and Middle Income Countries (LMIC). The challenge for these researchers is how they can make use of such data sets given their poor connectivity and infrastructure. The opportunity is the ability to perform leading edge research using these data sets and hence avoid having to invest substantial resources in generating the data sets. The offshoot of this will be to generate solutions to the substantial local problems encountered in these countries and create an educated workforce in data science. Cloud computing in particular may well close the infrastructural gap here. In this paper we discuss our experiences of teaching a variety of summer schools on data intensive analysis in bioinformatics in China, Namibia and Malaysia. On the basis of these experiences we propose that a larger series of summer schools in data science and cloud computing in LMIC would create a cadre of data scientists to start this process. We finally discuss the possibility of the provision of cloud computing resources where the usage costs are controlled so that it is affordable for LMIC researchers

Optimising the analysis of transcript data using high density oligonucleotide arrays and genomic DNA-based probe selection

Background: Affymetrix GeneChip arrays are widely used for transcriptomic studies in a diverse range of species. Each gene is represented on a GeneChip array by a probe-set, consisting of up to 16 probe-pairs. Signal intensities across probe-pairs within a probe-set vary in part due to different physical hybridisation characteristics of individual probes with their target labelled transcripts. We have previously developed a technique to study the transcriptomes of heterologous species based on hybridising genomic DNA (gDNA) to a GeneChip array designed for a different species, and subsequently using only those probes with good homology. Results: Here we have investigated the effects of hybridising homologous species gDNA to study the transcriptomes of species for which the arrays have been designed. Genomic DNA from Arabidopsis thaliana and rice (Oryza sativa) were hybridised to the Affymetrix Arabidopsis ATH1 and Rice Genome GeneChip arrays respectively. Probe selection based on gDNA hybridisation intensity increased the number of genes identified as significantly differentially expressed in two published studies of Arabidopsis development, and optimised the analysis of technical replicates obtained from pooled samples of RNA from rice. Conclusion: This mixed physical and bioinformatics approach can be used to optimise estimates of gene expression when using GeneChip arrays

Yeast m6 A methylated mRNAs are enriched on translating ribosomes during meiosis, and under rapamycin treatment

Interest in mRNA methylation has exploded in recent years. The sudden interest in a 40 year old discovery was due in part to the finding of FTO’s (Fat Mass Obesity) N6-methyladenosine (m6 A) deaminase activity, thus suggesting a link between obesity-associated diseases and the presence of m6 A in mRNA. Another catalyst of the sudden rise in mRNA methylation research was the release of mRNA methylomes for human, mouse and Saccharomyces cerevisiae. However, the molecular function, or functions of this mRNA ‘epimark’ remain to be discovered. There is supportive evidence that m6 A could be a mark for mRNA degradation due to its binding to YTH domain proteins, and consequently being chaperoned to P bodies. Nonetheless, only a subpopulation of the methylome was found binding to YTHDF2 in HeLa cells.The model organism Saccharomyces cerevisiae, has only one YTH domain protein (Pho92, Mrb1), which targets PHO4 transcripts for degradation under phosphate starvation. However, mRNA methylation is only found under meiosis inducing conditions, and PHO4 transcripts are apparently non-methylated. In this paper we set out to investigate if m6 A could function alternatively to being a degradation mark in S. cerevisiae; we also sought to test whether it can be induced under non-standard sporulation conditions. We find a positive association between the presence of m6 A and message translatability. We also find m6 A induction following prolonged rapamycin treatment

Complete Genome Sequence of Vibrio coralliilyticus Strain OCN014, Isolated from a Diseased Coral at Palmyra Atoll

Vibrio coralliilyticus is a marine gammaproteobacterium that has been implicated as an etiological agent of disease for multiple coral genera on reefs worldwide. We report the complete genome of V. coralliilyticus strain OCN014, isolated from a diseased Acropora cytherea colony off the western reef terrace of Palmyra Atoll

The Role of Palliative Surgery for Malignant Bowel Obstruction and Perforation in Advanced Microsatellite Instability-High Colorectal Carcinoma in the Era of Immunotherapy: Case Report.

The role of palliative surgery in the management of acute complications in patients with disseminated malignancy remains controversial given the complexity of assessing acute surgical risk and long-term oncologic outcome. With the emergence of checkpoint blockade immunotherapy, there appears to be an increasing role for historically palliative procedures as a bridge to systemic immunotherapy. This is especially evident in advanced microsatellite instability-high (MSI-H) colorectal cancer where malignant obstruction and fistula formation are more common and where immunotherapy with checkpoint blockade (anti-PD-1/PD-L1, anti-CTLA-4) has a high response rate with potential for favorable oncologic outcomes. We present a series of three patients with MSI-H metastatic colorectal cancer complicated by malignant bowel obstruction and fistula formation, who having progressed on standard chemotherapy, underwent palliative intervention as a bridge to immune checkpoint blockade with durable and clinically meaningful anti-cancer responses. These cases highlight the need to re-evaluate the role of historically palliative operations in the setting of disease progression for immunotherapy-responsive tumors

Using genomic DNA-based probe-selection to improve the sensitivity of high-density oligonucleotide arrays when applied to heterologous species

High-density oligonucleotide (oligo) arrays are a powerful tool for transcript profiling. Arrays based on GeneChip® technology are amongst the most widely used, although GeneChip® arrays are currently available for only a small number of plant and animal species. Thus, we have developed a method to improve the sensitivity of high-density oligonucleotide arrays when applied to heterologous species and tested the method by analysing the transcriptome of Brassica oleracea L., a species for which no GeneChip® array is available, using a GeneChip® array designed for Arabidopsis thaliana (L.) Heynh. Genomic DNA from B. oleracea was labelled and hybridised to the ATH1-121501 GeneChip® array. Arabidopsis thaliana probe-pairs that hybridised to the B. oleracea genomic DNA on the basis of the perfect-match (PM) probe signal were then selected for subsequent B. oleracea transcriptome analysis using a .cel file parser script to generate probe mask files. The transcriptional response of B. oleracea to a mineral nutrient (phosphorus; P) stress was quantified using probe mask files generated for a wide range of gDNA hybridisation intensity thresholds. An example probe mask file generated with a gDNA hybridisation intensity threshold of 400 removed > 68 % of the available PM probes from the analysis but retained >96 % of available A. thaliana probe-sets. Ninety-nine of these genes were then identified as significantly regulated under P stress in B. oleracea, including the homologues of P stress responsive genes in A. thaliana. Increasing the gDNA hybridisation intensity thresholds up to 500 for probe-selection increased the sensitivity of the GeneChip® array to detect regulation of gene expression in B. oleracea under P stress by up to 13-fold. Our open-source software to create probe mask files is freely available http://affymetrix.arabidopsis.info/xspecies/ webcite and may be used to facilitate transcriptomic analyses of a wide range of plant and animal species in the absence of custom arrays

Professional Organizations and Healthcare Industry Support: Ethical Conflict?

A good deal of attention has been recently focused on the presumed advertising excesses of the healthcare industry in its promotion techniques to healthcare professionals, whether through offering gratuities such as gifts, honoraria, or travel support2-6 or through deception. Two basic concerns have been expressed: Does the acceptance of gratuities bias the recipient, tainting his or her responsibilities as the patient's agent? Does acceptance of the gratuity by the healthcare professional contribute to the high cost of healthcare products? The California Society of Hospital Pharmacists was recently asked by its members to formulate a policy for an appropriate relationship between the Society and the healthcare industry, addressing these concerns. In formulating its policy, it became clear that the Society depended on healthcare industry support, gathered through journal advertising, fees for booths at its various educational events, and grants for speaker

A cross-species gene expression marker-based genetic map and QTL analysis in bambara groundnut

Bambara groundnut (Vigna subterranea (L.) Verdc.) is an underutilised legume crop, which has long been recognised as a protein-rich and drought-tolerant crop, used extensively in Sub-Saharan Africa. The aim of the study was to identify quantitative trait loci (QTL) involved in agronomic and drought-related traits using an expression marker-based genetic map based on major crop resources developed in soybean. The gene expression markers (GEMs) were generated at the (unmasked) probe-pair level after cross-hybridisation of bambara groundnut leaf RNA to the Affymetrix Soybean Genome GeneChip. A total of 753 markers grouped at an LOD (Logarithm of odds) of three, with 527 markers mapped into linkage groups. From this initial map, a spaced expression marker-based genetic map consisting of 13 linkage groups containing 218 GEMs, spanning 982.7 cM (centimorgan) of the bambara groundnut genome, was developed. Of the QTL detected, 46% were detected in both control and drought treatment populations, suggesting that they are the result of intrinsic trait differences between the parental lines used to construct the cross, with 31% detected in only one of the conditions. The present GEM map in bambara groundnut provides one technically feasible route for the translation of information and resources from major and model plant species to underutilised and resource-poor crops