Rapid reversal of a potentially constraining genetic covariance between leaf and flower traits in Silene latifolia.

Genetic covariance between two traits generates correlated responses to selection, and may either enhance or constrain adaptation. Silene latifolia exhibits potentially constraining genetic covariance between specific leaf area (SLA) and flower number in males. Flower number is likely to increase via fecundity selection but the correlated increase in SLA increases mortality, and SLA is under selection to decrease in dry habitats. We selected on trait combinations in two selection lines for four generations to test whether genetic covariance could be reduced without significantly altering trait means. In one selection line, the genetic covariance changed sign and eigenstructure changed significantly, while in the other selection line eigenstructure remained similar to the control line. Changes in genetic variance-covariance structure are therefore possible without the introduction of new alleles, and the responses we observed suggest that founder effects and changes in frequency of alleles of major effect may be acting to produce the changes.

Internet-Based Assessment of Oncology Health Care Professional Learning Style and Optimization of Materials for Web-Based Learning: Controlled Trial With Concealed Allocation.

BACKGROUND: Precision medicine has resulted in increasing complexity in the treatment of cancer. Web-based educational materials can help address the needs of oncology health care professionals seeking to understand up-to-date treatment strategies. OBJECTIVE: This study aimed to assess learning styles of oncology health care professionals and to determine whether learning style-tailored educational materials lead to enhanced learning. METHODS: In all, 21,465 oncology health care professionals were invited by email to participate in the fully automated, parallel group study. Enrollment and follow-up occurred between July 13 and September 7, 2015. Self-enrolled participants took a learning style survey and were assigned to the intervention or control arm using concealed alternating allocation. Participants in the intervention group viewed educational materials consistent with their preferences for learning (reading, listening, and/or watching); participants in the control group viewed educational materials typical of the My Cancer Genome website. Educational materials covered the topic of treatment of metastatic estrogen receptor-positive (ER+) breast cancer using cyclin-dependent kinases 4/6 (CDK4/6) inhibitors. Participant knowledge was assessed immediately before (pretest), immediately after (posttest), and 2 weeks after (follow-up test) review of the educational materials. Study statisticians were blinded to group assignment. RESULTS: A total of 751 participants enrolled in the study. Of these, 367 (48.9%) were allocated to the intervention arm and 384 (51.1%) were allocated to the control arm. Of those allocated to the intervention arm, 256 (69.8%) completed all assessments. Of those allocated to the control arm, 296 (77.1%) completed all assessments. An additional 12 participants were deemed ineligible and one withdrew. Of the 552 participants, 438 (79.3%) self-identified as multimodal learners. The intervention arm showed greater improvement in posttest score compared to the control group (0.4 points or 4.0% more improvement on average; P=.004) and a higher follow-up test score than the control group (0.3 points or 3.3% more improvement on average; P=.02). CONCLUSIONS: Although the study demonstrated more learning with learning style-tailored educational materials, the magnitude of increased learning and the largely multimodal learning styles preferred by the study participants lead us to conclude that future content-creation efforts should focus on multimodal educational materials rather than learning style-tailored content.

My Cancer Genome: Evaluating an Educational Model to Introduce Patients and Caregivers to Precision Medicine Information.

This study tested an innovative model for creating consumer-level content about precision medicine based on health literacy and learning style principles. "Knowledge pearl" videos, incorporating multiple learning modalities, were created to explain genetic and cancer medicine concepts. Cancer patients and caregivers (n=117) were randomized to view professional-level content directly from the My Cancer Genome (MCG) website (Group A; control), content from MCG with knowledge pearls embedded (Group B), or a consumer translation, targeted at the sixth grade level, with knowledge pearls embedded (Group C). A multivariate analysis showed that Group C, but not Group B, showed greater knowledge gains immediately after viewing the educational material than Group A. Statistically significant group differences in test performance were no longer observed three weeks later. These findings suggest that adherence to health literacy and learning style principles facilitates comprehension of precision medicine concepts and that ongoing review of the educational information is necessary.

Guiding Oncology Patients Through the Maze of Precision Medicine.

As the role of genomics in health care grows, patients increasingly require adequate genetic literacy to fully engage in their care. This study investigated a model for delivering consumer-friendly genetic information to improve understanding of precision medicine using health literacy and learning style principles. My Cancer Genome (MCG), a freely available cancer decision support tool, was used as a testbed. MCG content on a melanoma tumor mutation, BRAF V600E, was translated to a 6th-grade reading level, incorporating multiple learning modalities. A total of 90 patients and caregivers were recruited from a melanoma clinic at an academic medical center and randomized to 3 groups. Group A (control) received an exact copy of text from MCG. Group B was given the same content with hyperlinks to videos explaining key genetic concepts, identified and labeled by the team as knowledge pearls. Group C received the translated content with the knowledge pearls embedded. Changes in knowledge were measured through pre and post questionnaires. Group C showed the greatest improvement in knowledge. The study results demonstrate that providing information based on health literacy and learning style principles can improve patients' understanding of genetic concepts, thus increasing their likelihood of taking an active role in any decision making concerning their health.

The Path(way) Less Traveled: A Pathway-Oriented Approach to Providing Information about Precision Cancer Medicine on My Cancer Genome.

This perspective describes the motivation, development, and implementation of pathway-based content for My Cancer Genome, an online precision medicine knowledge resource describing clinical implications of genetic alterations in cancer. As researchers uncover more about cancer pathogenesis, we are learning more not only about the specific genes and proteins involved but also about how those genes and proteins interact with others along cell signaling pathways. This knowledge has led researchers and clinicians to begin to think about cancer therapy using a pathway-based approach. To facilitate this approach, My Cancer Genome used a list of more than 800 cancer-related genes to identify 20 cancer-relevant pathways and then created content focused on demonstrating the therapeutic relevance of these pathways.

Beyond histology: translating tumor genotypes into clinically effective targeted therapies.

Increased understanding of intertumoral heterogeneity at the genomic level has led to significant advancements in the treatment of solid tumors. Functional genomic alterations conferring sensitivity to targeted therapies can take many forms, and appropriate methods and tools are needed to detect these alterations. This review provides an update on genetic variability among solid tumors of similar histologic classification, using non-small cell lung cancer and melanoma as examples. We also discuss relevant technological platforms for discovery and diagnosis of clinically actionable variants and highlight the implications of specific genomic alterations for response to targeted therapy.

Elimination of a genetic correlation between the sexes via artificial correlational selection.

Genetic correlations between the sexes can constrain the evolution of sexual dimorphism and be difficult to alter, because traits common to both sexes share the same genetic underpinnings. We tested whether artificial correlational selection favoring specific combinations of male and female traits within families could change the strength of a very high between-sex genetic correlation for flower size in the dioecious plant Silene latifolia. This novel selection dramatically reduced the correlation in two of three selection lines in fewer than five generations. Subsequent selection only on females in a line characterized by a lower between-sex genetic correlation led to a significantly lower correlated response in males, confirming the potential evolutionary impact of the reduced correlation. Although between-sex genetic correlations can potentially constrain the evolution of sexual dimorphism, our findings reveal that these constraints come not from a simple conflict between an inflexible genetic architecture and a pattern of selection working in opposition to it, but rather a complex relationship between a changeable correlation and a form of selection that promotes it. In other words, the form of selection on males and females that leads to sexual dimorphism may also promote the genetic phenomenon that limits sexual dimorphism.

Relaxed pollinator-mediated selection weakens floral integration in self-compatible taxa of Leavenworthia (Brassicaceae).

Natural selection should favor the integration of floral traits that enhance pollen export and import in plant populations that rely upon pollinators. If this is true, then phenotypic correlations between floral traits should weaken in self-fertilizing groups that do not require pollinator visitation to produce seed. We tested this hypothesis in Leavenworthia, a plant genus in which there have been multiple independent losses of the sporophytic self-incompatibility system found throughout the Brassicaceae. In particular, we conducted phylogenetically independent contrasts of floral trait correlations between two pairs of self-incompatible (SI) and self-compatible (SC) sister taxa. In support of the hypothesis that pollinator-mediated selection integrates floral traits, we found that both SC Leavenworthia taxa have weaker overall floral correlations in comparison to sister taxa that rely upon pollinators. The two independently derived SC Leavenworthia flowers have significantly weaker stamen-petal or pistil-petal correlations, respectively, whereas the stamen-pistil correlation remains constant. These patterns suggest that relaxation of pollinator-mediated selection weakens the integration of traits associated with pollen export and import. The retention of high stamen-pistil correlations in the SC taxa of Leavenworthia further implies that the integration of these traits is either constrained or maintained by selection favoring the successful transfer of pollen within flowers to secure self-pollination.