A transfer-learning approach to feature extraction from cancer transcriptomes with deep autoencoders

Publicado en Lecture Notes in Computer Science.The diagnosis and prognosis of cancer are among the more challenging tasks that oncology medicine deals with. With the main aim of fitting the more appropriate treatments, current personalized medicine focuses on using data from heterogeneous sources to estimate the evolu- tion of a given disease for the particular case of a certain patient. In recent years, next-generation sequencing data have boosted cancer prediction by supplying gene-expression information that has allowed diverse machine learning algorithms to supply valuable solutions to the problem of cancer subtype classification, which has surely contributed to better estimation of patient’s response to diverse treatments. However, the efficacy of these models is seriously affected by the existing imbalance between the high dimensionality of the gene expression feature sets and the number of sam- ples available for a particular cancer type. To counteract what is known as the curse of dimensionality, feature selection and extraction methods have been traditionally applied to reduce the number of input variables present in gene expression datasets. Although these techniques work by scaling down the input feature space, the prediction performance of tradi- tional machine learning pipelines using these feature reduction strategies remains moderate. In this work, we propose the use of the Pan-Cancer dataset to pre-train deep autoencoder architectures on a subset com- posed of thousands of gene expression samples of very diverse tumor types. The resulting architectures are subsequently fine-tuned on a col- lection of specific breast cancer samples. This transfer-learning approach aims at combining supervised and unsupervised deep learning models with traditional machine learning classification algorithms to tackle the problem of breast tumor intrinsic-subtype classification.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Survival processing in times of stress

Recent studies have found that processing information according to an evolutionary relevant (i.e., survival) scenario improves its subsequent memorability, potentially as a result of fitness advantages gained in the ancestral past. So far, research has not revealed much about any proximate mechanisms that might underlie this so-called survival processing advantage in memory. Intriguingly, research has shown that the memorability of stressful situations is enhanced via the release of stress hormones acting on brain regions involved in memory. Since survival situations habitually involve some degree of stress, in the present study, we investigated whether stress serves as a proximate mechanism to promote survival processing. Participants rated words for their relevance to either a survival or a neutral (moving) scenario after they had been exposed to a psychosocial stressor or a no-stress control condition. Surprise retention tests immediately following the rating task revealed that survival processing and acute stress independently boosted memory performance. These results therefore suggest that stress does not serve as a proximate mechanism of the survival processing advantage in memory

Adaptive memory: Stereotype activation is not enough

Studies have shown that survival processing leads to superior memorability. The aim of the present study was to examine whether this survival recall advantage might result from stereotype activation. To test this hypothesis, we conducted a pilot study and two experiments in which participants were primed with stereotypes (Experiment 1, professor and elderly person; Experiment 2, survival-stereotype). In Experiment 1, 120 undergraduates were randomly assigned to a survival, professor stereotype, elderly person stereotype, or moving scenario and rated words for their relevance to the imagined scenario. In Experiment 2, 75 undergraduates were given a survival, survival-stereotype (based on our pilot study), or moving scenario. Both experiments showed that survival processing leads to a greater recall advantage over the stereotype groups and control group. These data indicate that the mere activation of stereotypes cannot explain the survival recall advantage

Climate Variability and Ross River Virus Transmission in Townsville Region, Australia 1985 to 1996

Background How climate variability affects the transmission of infectious diseases at a regional level remains unclear. In this paper, we assessed the impact of climate variation on the Ross River virus (RRv) transmission in the Townsville region, Queensland, north-east Australia. Methods Population-based information was obtained on monthly variations in RRv cases, climatic factors, sea level, and population growth between 1985 and 1996. Cross-correlations were computed for a series of associations between climate variables (rainfall, maximum temperature, minimum temperature, relative humidity and high tide) and the monthly incidence of RRv disease over a range of time lags. The impact of climate variability on RRv transmission was assessed using the seasonal auto-regressive integrated moving average (SARIMA) model. Results There were significant correlations of the monthly incidence of RRv to rainfall, maximum temperature, minimum temperature and relative humidity, all at a lag of 2 months, and high tide in the current month. The results of SARIMA models show that monthly average rainfall (β=0.0012, p=0.04) and high tide (β=0.0262, p=0.01) were significantly associated with RRv transmission, although temperature and relative humidity did not seem to have played an important role in the Townsville region. Conclusions Rainfall, and high tide were likely to be key determinants of RRv transmission in the Townsville region

Targeted knock-down of miR21 primary transcripts using snoMEN vectors induces apoptosis in human cancer cell lines

We have previously reported an antisense technology, 'snoMEN vectors', for targeted knock-down of protein coding mRNAs using human snoRNAs manipulated to contain short regions of sequence complementarity with the mRNA target. Here we characterise the use of snoMEN vectors to target the knock-down of micro RNA primary transcripts. We document the specific knock-down of miR21 in HeLa cells using plasmid vectors expressing miR21-targeted snoMEN RNAs and show this induces apoptosis. Knock-down is dependent on the presence of complementary sequences in the snoMEN vector and the induction of apoptosis can be suppressed by over-expression of miR21. Furthermore, we have also developed lentiviral vectors for delivery of snoMEN RNAs and show this increases the efficiency of vector transduction in many human cell lines that are difficult to transfect with plasmid vectors. Transduction of lentiviral vectors expressing snoMEN targeted to pri-miR21 induces apoptosis in human lung adenocarcinoma cells, which express high levels of miR21, but not in human primary cells. We show that snoMEN-mediated suppression of miRNA expression is prevented by siRNA knock-down of Ago2, but not by knock-down of Ago1 or Upf1. snoMEN RNAs colocalise with Ago2 in cell nuclei and nucleoli and can be co-immunoprecipitated from nuclear extracts by antibodies specific for Ago2

Urolithiasis and psoas abscess in a 2-year-old boy with type 1 glycogen storage disease

We report on a pyogenic psoas abscess secondary to an impacted calcium oxalate ureteric stone in a 2-year-old boy with glycogen storage disease type 1 (GSD-1). The patient had a drainage of the abscess through a flank incision followed by percutaneous nephrostomy and open ureterolithotomy. Metabolic acidosis, hyperuricemia, hypocitraturia, and hypercalciuria appear to be significant in the pathogenesis of urolithiasis in patients with GSD-1. Regular ultrasonography of the abdomen along with optimal metabolic control may delay or prevent urolithiasis and its complications in GSD-1 patients

Protocol for population testing of an Internet-based Personalised Decision Support system for colorectal cancer screening

Extent: 8p.Background: Australia has a comparatively high incidence of colorectal (bowel) cancer; however, population screening uptake using faecal occult blood test (FOBT) remains low. This study will determine the impact on screening participation of a novel, Internet-based Personalised Decision Support (PDS) package. The PDS is designed to measure attitudes and cognitive concerns and provide people with individually tailored information, in real time, that will assist them with making a decision to screen. The hypothesis is that exposure to (tailored) PDS will result in greater participation in screening than participation following exposure to non-tailored PDS or resulting from the current non-tailored, paper-based approach. Methods/design: A randomised parallel trial comprising three arms will be conducted. Men and women aged 50-74 years (N = 3240) will be recruited. They must have access to the Internet; have not had an FOBT within the previous 12 months, or sigmoidoscopy or colonoscopy within the previous 5 years; have had no clinical diagnosis of bowel cancer. Groups 1 and 2 (PDS arms) will access a website and complete a baseline survey measuring decision-to-screen stage, attitudes and cognitive concerns and will receive immediate feedback; Group 1 will receive information 'tailored' to their responses in the baseline survey and group 2 will received 'non-tailored' bowel cancer information. Respondents in both groups will subsequently receive an FOBT kit. Group 3 (usual practice arm) will complete a paper-based version of the baseline survey and respondents will subsequently receive 'non-tailored' paper-based bowel cancer information with accompanying FOBT kit. Following despatch of FOBTs, all respondents will be requested to complete an endpoint survey. Main outcome measures are (1) completion of FOBT and (2) change in decision-to-screen stage. Secondary outcomes include satisfaction with decision and change in attitudinal scores from baseline to endpoint. Analyses will be performed using Chi-square tests, analysis of variance and log binomial generalized linear models as appropriate. Discussion: It is necessary to restrict participants to Internet users to provide an appropriately controlled evaluation of PDS. Once efficacy of the approach has been established, it will be important to evaluate effectiveness in the wider at-risk population, and to identify barriers to its implementation in those settings.Carlene J Wilson, Ingrid HK Flight, Ian T Zajac, Deborah Turnbull, Graeme P Young, Stephen R Cole, Tess Gregor

Identification of Cancer Cell-Line Origins Using Fluorescence Image-Based Phenomic Screening

Universal phenotyping techniques that can discriminate among various states of biological systems have great potential. We applied 557 fluorescent library compounds to NCI's 60 human cancer cell-lines (NCI-60) to generate a systematic fluorescence phenotypic profiling data. By the kinetic fluorescence intensity analysis, we successfully discriminated the organ origin of all the 60 cell-lines