POLYA: A TOOL FOR ADJUDICATING COMPETING ANNOTATIONS OF BIOLOGICAL SEQUENCES

Annotation of a biological sequence is usually performed by aligning that sequence to a database of known sequence elements. When that database contains elements that are highly similar to each other, the proper annotation may be ambiguous, because several entries in the database produce high-scoring alignments. Typical annotation methods work by assigning a label based on the candidate annotation with the highest alignment score; this can overstate annotation certainty, mislabel boundaries, and fails to identify large scale rearrangements or insertions within the annotated sequence. Here, I present a new software tool, PolyA, that adjudicates between competing alignment-based annotations by computing estimates of annotation confidence, identifying a trace with maximal confidence, and recursively splicing/stitching inserted elements. PolyA communicates annotation certainty, identifies large scale rearrangements, and detects boundaries between neighboring elements

Evaluating the rapid emergence of daptomycin resistance in Corynebacterium: A multicenter study

Members of the genu

A Practical Guide for Managing Interdisciplinary Teams: Lessons Learned from Coupled Natural and Human Systems Research

Interdisciplinary team science is essential to address complex socio-environmental questions, but it also presents unique challenges. The scientific literature identifies best practices for high-level processes in team science, e.g., leadership and team building, but provides less guidance about practical, day-to-day strategies to support teamwork, e.g., translating jargon across disciplines, sharing and transforming data, and coordinating diverse and geographically distributed researchers. This article offers a case study of an interdisciplinary socio-environmental research project to derive insight to support team science implementation. We evaluate the project’s inner workings using a framework derived from the growing body of literature for team science best practices, and derive insights into how best to apply team science principles to interdisciplinary research. We find that two of the most useful areas for proactive planning and coordinated leadership are data management and co-authorship. By providing guidance for project implementation focused on these areas, we contribute a pragmatic, detail-oriented perspective on team science in an effort to support similar projects

Training macrosystems scientists requires both interpersonal and technical skills

Macrosystems science strives to integrate patterns and processes that span regional to continental scales. The scope of such research often necessitates the involvement of large interdisciplinary and/or multi-institutional teams composed of scientists across a range of career stages, a diversity that requires researchers to hone both technical and interpersonal skills. We surveyed participants in macrosystems projects funded by the US National Science Foundation to assess the perceived importance of different skills needed in their research, as well as the types of training they received. Survey results revealed a mismatch between the skills participants perceive as important and the training they received, particularly for interpersonal and management skills. We highlight lessons learned from macrosystems training case studies, explore avenues for further improvement of undergraduate and graduate education, and discuss other training opportunities for macrosystems scientists. Given the trend toward interdisciplinary research beyond the macrosystems community, these insights are broadly applicable for scientists involved in diverse, collaborative projects.https://esajournals.onlinelibrary.wiley.com/doi/full/10.1002/fee.228

Expanding the diversity of mycobacteriophages: insights into genome architecture and evolution.

Mycobacteriophages are viruses that infect mycobacterial hosts such as Mycobacterium smegmatis and Mycobacterium tuberculosis. All mycobacteriophages characterized to date are dsDNA tailed phages, and have either siphoviral or myoviral morphotypes. However, their genetic diversity is considerable, and although sixty-two genomes have been sequenced and comparatively analyzed, these likely represent only a small portion of the diversity of the mycobacteriophage population at large. Here we report the isolation, sequencing and comparative genomic analysis of 18 new mycobacteriophages isolated from geographically distinct locations within the United States. Although no clear correlation between location and genome type can be discerned, these genomes expand our knowledge of mycobacteriophage diversity and enhance our understanding of the roles of mobile elements in viral evolution. Expansion of the number of mycobacteriophages grouped within Cluster A provides insights into the basis of immune specificity in these temperate phages, and we also describe a novel example of apparent immunity theft. The isolation and genomic analysis of bacteriophages by freshman college students provides an example of an authentic research experience for novice scientists

Genetic Testing to Inform Epilepsy Treatment Management From an International Study of Clinical Practice

IMPORTANCE: It is currently unknown how often and in which ways a genetic diagnosis given to a patient with epilepsy is associated with clinical management and outcomes. OBJECTIVE: To evaluate how genetic diagnoses in patients with epilepsy are associated with clinical management and outcomes. DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective cross-sectional study of patients referred for multigene panel testing between March 18, 2016, and August 3, 2020, with outcomes reported between May and November 2020. The study setting included a commercial genetic testing laboratory and multicenter clinical practices. Patients with epilepsy, regardless of sociodemographic features, who received a pathogenic/likely pathogenic (P/LP) variant were included in the study. Case report forms were completed by all health care professionals. EXPOSURES: Genetic test results. MAIN OUTCOMES AND MEASURES: Clinical management changes after a genetic diagnosis (ie, 1 P/LP variant in autosomal dominant and X-linked diseases; 2 P/LP variants in autosomal recessive diseases) and subsequent patient outcomes as reported by health care professionals on case report forms. RESULTS: Among 418 patients, median (IQR) age at the time of testing was 4 (1-10) years, with an age range of 0 to 52 years, and 53.8% (n = 225) were female individuals. The mean (SD) time from a genetic test order to case report form completion was 595 (368) days (range, 27-1673 days). A genetic diagnosis was associated with changes in clinical management for 208 patients (49.8%) and usually (81.7% of the time) within 3 months of receiving the result. The most common clinical management changes were the addition of a new medication (78 [21.7%]), the initiation of medication (51 [14.2%]), the referral of a patient to a specialist (48 [13.4%]), vigilance for subclinical or extraneurological disease features (46 [12.8%]), and the cessation of a medication (42 [11.7%]). Among 167 patients with follow-up clinical information available (mean [SD] time, 584 [365] days), 125 (74.9%) reported positive outcomes, 108 (64.7%) reported reduction or elimination of seizures, 37 (22.2%) had decreases in the severity of other clinical signs, and 11 (6.6%) had reduced medication adverse effects. A few patients reported worsening of outcomes, including a decline in their condition (20 [12.0%]), increased seizure frequency (6 [3.6%]), and adverse medication effects (3 [1.8%]). No clinical management changes were reported for 178 patients (42.6%). CONCLUSIONS AND RELEVANCE: Results of this cross-sectional study suggest that genetic testing of individuals with epilepsy may be materially associated with clinical decision-making and improved patient outcomes