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Background Accurate identification of real somatic variants is a primary part of cancer genome studies and precision oncology. However, artifacts introduced in various steps of sequencing obfuscate confidence in variant calling. Current computational approaches to variant filtering involve intensive interrogation of Binary Alignment Map (BAM) files and require massive computing power, data storage, and manual labor. Recently, mutational signatures associated with sequencing artifacts have been extracted by the Pan-cancer Analysis of Whole Genomes (PCAWG) study. These spectrums can be used to evaluate refinement quality of a given set of somatic mutations. Results Here we introduce a novel variant refinement software, FIREVAT (FInding REliable Variants without ArTifacts), which uses known spectrums of sequencing artifacts extracted from one of the largest publicly available catalogs of human tumor samples. FIREVAT performs a quick and efficient variant refinement that accurately removes artifacts and greatly improves the precision and specificity of somatic calls. We validated FIREVAT refinement performance using orthogonal sequencing datasets totaling 384 tumor samples with respect to ground truth. Our novel method achieved the highest level of performance compared to existing filtering approaches. Application of FIREVAT on additional 308 The Cancer Genome Atlas (TCGA) samples demonstrated that FIREVAT refinement leads to identification of more biologically and clinically relevant mutational signatures as well as enrichment of sequence contexts associated with experimental errors. FIREVAT only requires a Variant Call Format file (VCF) and generates a comprehensive report of the variant refinement processes and outcomes for the user. Conclusions In summary, FIREVAT facilitates a novel refinement strategy using mutational signatures to distinguish artifactual point mutations called in human cancer samples. We anticipate that FIREVAT results will further contribute to precision oncology efforts that rely on accurate identification of variants, especially in the context of analyzing mutational signatures that bear prognostic and therapeutic significance. FIREVAT is freely available at https://github.com/cgab-ncc/FIREVAT

BACKGROUND There is considerable scientific interest in finding new and innovative ways to capture rapid fluctuations in functioning within individuals with bipolar disorder (BD), a severe, recurrent mental disorder associated with frequent shifts in symptoms and functioning. The use of smartphones can provide valid and real-world tools for use in measurement-based care and could be used to inform more personalized treatment options for this group, which can improve standard of care. OBJECTIVE We examined the feasibility and usability of a smartphone to capture daily fluctuations in mood within BD and to relate daily self-rated mood to smartphone use behaviors indicative of psychomotor activity or symptoms of the illness. METHODS Participants were 26 individuals with BD and 12 healthy control individuals who were recruited from the Prechter Longitudinal Study of BD. All were given a smartphone with a custom-built app and prompted twice a day to complete questions of mood for 28 days. The app automatically and unobtrusively collected phone usage data. A poststudy satisfaction survey was also completed. RESULTS Our sample showed a very high adherence rate to the daily momentary assessments (91% of the 58 prompts completed). Multivariate mixed effect models showed that an increase in rapid thoughts over time was associated with a decrease in outgoing text messages (β=–.02; P=.04), and an increase in impulsivity self-ratings was related to a decrease in total call duration (β=–.29; P=.02). Participants generally reported positive experiences using the smartphone and completing daily prompts. CONCLUSIONS Use of mobile technology shows promise as a way to collect important clinical information that can be used to inform treatment decision making and monitor outcomes in a manner that is not overly burdensome to the patient or providers, highlighting its potential use in measurement-based care.

BACKGROUND: HeartSteps is an mHealth intervention that encourages regular walking via activity suggestions tailored to the individuals’ current context. PURPOSE: We conducted a micro-randomized trial (MRT) to evaluate the efficacy of HeartSteps’ activity suggestions to optimize the intervention. METHODS: We conducted a 6-week MRT with 44 adults. Contextually tailored suggestions could be delivered up to five times per day at user-selected times. At each of these five times, for each participant on each day of the study, HeartSteps randomized whether to provide an activity suggestion, and, if so, whether to provide a walking or an antisedentary suggestion. We used a centered and weighted least squares method to analyze the effect of suggestions on the 30-min step count following suggestion randomization. RESULTS: Averaging over study days and types of activity suggestions, delivering a suggestion versus no suggestion increased the 30-min step count by 14% (p = .06), 35 additional steps over the 253-step average. The effect was not evenly distributed in time. Providing any type of suggestion versus no suggestion initially increased the step count by 66% (167 steps; p < .01), but this effect diminished over time. Averaging over study days, delivering a walking suggestion versus no suggestion increased the average step count by 24% (59 steps; p = .02). This increase was greater at the start of study (107% or 271 additional steps; p < .01), but decreased over time. Antisedentary suggestions had no detectable effect on the 30-min step count. CONCLUSION: Contextually tailored walking suggestions are a promising way of initiating bouts of walking throughout the day. CLINICAL TRIAL INFORMATION: This study was registered on ClinicalTrials.gov number NCT03225521.

Somatic genome mutations occur due to combinations of various intrinsic/extrinsic mutational processes and DNA repair mechanisms. Different molecular processes frequently generate different signatures of somatic mutations in their own favored contexts. As a result, the regional somatic mutation rate is dependent on the local DNA sequence, the DNA replication/RNA transcription dynamics and epigenomic chromatin organization landscape in the genome. Here, we propose an online computational framework, termed Mutalisk, which correlates somatic mutations with various genomic, transcriptional and epigenomic features in order to understand mutational processes that contribute to the generation of the mutations. This user-friendly tool explores the presence of localized hypermutations (kataegis), dissects the spectrum of mutations into the maximum likelihood combination of known mutational signatures and associates the mutation density with numerous regulatory elements in the genome. As a result, global patterns of somatic mutations in any query sample can be efficiently screened, thus enabling a deeper understanding of various mutagenic factors. This tool will facilitate more effective downstream analyses of cancer genome sequences to elucidate the diversity of mutational processes underlying the development and clonal evolution of cancer cells. Mutalisk is freely available at http://mutalisk.org.

There is a growing interest in leveraging the prevalence of mobile technology to improve health by delivering momentary, contextualized interventions to individuals' smartphones. A just-in-time adaptive intervention (JITAI) adjusts to an individual's changing state and/or context to provide the right treatment, at the right time, in the right place. Micro-randomized trials (MRTs) allow for the collection of data which aid in the construction of an optimized JITAI by sequentially randomizing participants to different treatment options at each of many decision points throughout the study. Often, this data is collected passively using a mobile phone. To assess the causal effect of treatment on a near-term outcome, care must be taken when designing the data collection system to ensure it is of appropriately high quality. Here, we make several recommendations for collecting and managing data from an MRT. We provide advice on selecting which features to collect and when, choosing between "agents" to implement randomization, identifying sources of missing data, and overcoming other novel challenges. The recommendations are informed by our experience with HeartSteps, an MRT designed to test the effects of an intervention aimed at increasing physical activity in sedentary adults. We also provide a checklist which can be used in designing a data collection system so that scientists can focus more on their questions of interest, and less on cleaning data., Author accepted manuscript