Quantifying alternative splicing from paired-end RNA-sequencing data

RNA-sequencing has revolutionized biomedical research and, in particular, our ability to study gene alternative splicing. The problem has important implications for human health, as alternative splicing may be involved in malfunctions at the cellular level and multiple diseases. However, the high-dimensional nature of the data and the existence of experimental biases pose serious data analysis challenges. We find that the standard data summaries used to study alternative splicing are severely limited, as they ignore a substantial amount of valuable information. Current data analysis methods are based on such summaries and are hence suboptimal. Further, they have limited flexibility in accounting for technical biases. We propose novel data summaries and a Bayesian modeling framework that overcome these limitations and determine biases in a nonparametric, highly flexible manner. These summaries adapt naturally to the rapid improvements in sequencing technology. We provide efficient point estimates and uncertainty assessments. The approach allows to study alternative splicing patterns for individual samples and can also be the basis for downstream analyses. We found a severalfold improvement in estimation mean square error compared popular approaches in simulations, and substantially higher consistency between replicates in experimental data. Our findings indicate the need for adjusting the routine summarization and analysis of alternative splicing RNA-seq studies. We provide a software implementation in the R package casper.Comment: Published in at http://dx.doi.org/10.1214/13-AOAS687 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org). With correction

Quantifying alternative splicing from paired-end RNA-sequencing data

RNA-sequencing has revolutionized biomedical research and, in particular, our ability to study gene alternative splicing. The problem has important implications for human health, as alternative splicing is involved in malfunctions at the cellular level and multiple diseases. However, the high-dimensional nature of the data and the existence of experimental biases pose serious data analysis challenges. We find that the standard data summaries used to study alternative splicing are severely limited, as they ignore a substantial amount of valuable information. Current data analysis methods are based on such summaries and are hence sub-optimal. Further, they have limited flexibility in accounting for technical biases. We propose novel data summaries and a Bayesian modeling framework that overcome these limitations and determine biases in a non-parametric, data-dependent manner. These summaries adapt naturally to the rapid improvements in sequencing technology. We provide efficient point estimates and uncertainty assessments. The approach allows to study alternative splicing patterns for individual samples and can also be the basis for downstream differential expression analysis. We found an over 5 fold improvement in estimation mean square error compared to a popular approach in simulations, and substantially higher correlations between replicates in experimental data. Our findings indicate the need for modifying the routine summarization and analysis of alternative splicing RNA-seq studies. We provide a software implementation in the R package casper

Pediatric oncologists' perspectives on the use of complementary medicine in pediatric cancer patients in Switzerland: A national survey-based cross-sectional study

BACKGROUND There is a widespread use of complementary therapies among pediatric cancer patients. Previous studies provided evidence that communication between pediatric oncologists (POs) and patients/families about the use of these therapies is often incomplete. Furthermore, nationwide studies on this topic are rare. AIMS We assessed POs' perspectives on the use of complementary medicine (CM) in Switzerland, on the basis of an edited survey previously used in a nationwide study. METHODS AND RESULTS A link to an online survey was sent by e-mail to each of the fifty-two eligible pediatric oncologists in all nine Swiss Pediatric Oncology Group (SPOG) centers. Eligible respondents were board-certified (Switzerland or abroad) POs currently working at a SPOG center. The survey was available for a total period of 2 months. We received 29 filled questionnaires (overall response rate: 56%). Most POs (59%) indicated that they ask more than 50% of their patients about CM use. Frequent reasons for not asking about the use of CM were i) forgetting to ask (55%), ii) lack of knowledge on the subject (31%), and iii) lack of time (24%). More than every second PO (55%) reported having a lack of knowledge on the subject. A majority of POs (66% to 76%) indicated interest in learning more about specific CM topics (cannabinoids, hypnosis and relaxation, music therapy, herbal medicine, acupuncture, meditation, and yoga). More information and specific training opportunities on the use of CM was deemed important by 76% to 97% of POs. CONCLUSION POs working in Switzerland identify complementary therapies as an important subject. Swiss POs are willing to acquire more knowledge on CM. More training seems to be necessary in order to increase awareness about the topic, to enhance communication about complementary therapies and thus to improve patient care

Pediatric oncologists' perspectives on the use of complementary medicine in pediatric cancer patients in Switzerland: A national survey-based cross-sectional study.

BACKGROUND There is a widespread use of complementary therapies among pediatric cancer patients. Previous studies provided evidence that communication between pediatric oncologists (POs) and patients/families about the use of these therapies is often incomplete. Furthermore, nationwide studies on this topic are rare. AIMS We assessed POs' perspectives on the use of complementary medicine (CM) in Switzerland, on the basis of an edited survey previously used in a nationwide study. METHODS AND RESULTS A link to an online survey was sent by e-mail to each of the fifty-two eligible pediatric oncologists in all nine Swiss Pediatric Oncology Group (SPOG) centers. Eligible respondents were board-certified (Switzerland or abroad) POs currently working at a SPOG center. The survey was available for a total period of 2 months. We received 29 filled questionnaires (overall response rate: 56%). Most POs (59%) indicated that they ask more than 50% of their patients about CM use. Frequent reasons for not asking about the use of CM were i) forgetting to ask (55%), ii) lack of knowledge on the subject (31%), and iii) lack of time (24%). More than every second PO (55%) reported having a lack of knowledge on the subject. A majority of POs (66% to 76%) indicated interest in learning more about specific CM topics (cannabinoids, hypnosis and relaxation, music therapy, herbal medicine, acupuncture, meditation, and yoga). More information and specific training opportunities on the use of CM was deemed important by 76% to 97% of POs. CONCLUSION POs working in Switzerland identify complementary therapies as an important subject. Swiss POs are willing to acquire more knowledge on CM. More training seems to be necessary in order to increase awareness about the topic, to enhance communication about complementary therapies and thus to improve patient care

Pediatric oncologists' perspectives on the use of complementary medicine in pediatric cancer patients in Switzerland: A national survey-based cross-sectional study

Background: There is a widespread use of complementary therapies among pediatric cancer patients. Previous studies provided evidence that communication between pediatric oncologists (POs) and patients/families about the use of these therapies is often incomplete. Furthermore, nationwide studies on this topic are rare. Aims: We assessed POs' perspectives on the use of complementary medicine (CM) in Switzerland, on the basis of an edited survey previously used in a nationwide study. Methods and results: A link to an online survey was sent by e-mail to each of the fifty-two eligible pediatric oncologists in all nine Swiss Pediatric Oncology Group (SPOG) centers. Eligible respondents were board-certified (Switzerland or abroad) POs currently working at a SPOG center. The survey was available for a total period of 2 months. We received 29 filled questionnaires (overall response rate: 56%). Most POs (59%) indicated that they ask more than 50% of their patients about CM use. Frequent reasons for not asking about the use of CM were i) forgetting to ask (55%), ii) lack of knowledge on the subject (31%), and iii) lack of time (24%). More than every second PO (55%) reported having a lack of knowledge on the subject. A majority of POs (66% to 76%) indicated interest in learning more about specific CM topics (cannabinoids, hypnosis and relaxation, music therapy, herbal medicine, acupuncture, meditation, and yoga). More information and specific training opportunities on the use of CM was deemed important by 76% to 97% of POs. Conclusion: POs working in Switzerland identify complementary therapies as an important subject. Swiss POs are willing to acquire more knowledge on CM. More training seems to be necessary in order to increase awareness about the topic, to enhance communication about complementary therapies and thus to improve patient care.</p