Charting Single Cell Lineage Dynamics and Mutation Networks via Homing CRISPR.

Single cell lineage tracing, essential for unraveling cellular dynamics in disease evolution is critical for developing targeted therapies. CRISPR-Cas9, known for inducing permanent and cumulative mutations, is a cornerstone in lineage tracing. The novel homing guide RNA (hgRNA) technology enhances this by enabling dynamic retargeting and facilitating ongoing genetic modifications. Charting these mutations, especially through successive hgRNA edits, poses a significant challenge. Our solution, LINEMAP, is a computational framework designed to trace and map these mutations with precision. LINEMAP meticulously discerns mutation alleles at single-cell resolution and maps their complex interrelationships through a mutation evolution network. By utilizing a Markov Process model, we can predict mutation transition probabilities, revealing potential mutational routes and pathways. Our reconstruction algorithm, anchored in the Markov model's attributes, reconstructs cellular lineage pathways, shedding light on the cell's evolutionary journey to the minutiae of single-cell division. Our findings reveal an intricate network of mutation evolution paired with a predictive Markov model, advancing our capability to reconstruct single-cell lineage via hgRNA. This has substantial implications for advancing our understanding of biological mechanisms and propelling medical research forward.

Preventing inpatient falls with injuries using integrative machine learning prediction: a cohort study.

Patient falls during hospitalization can lead to severe injuries and remain one of the most vexing patient-safety problems facing hospitals. They lead to increased medical care costs, lengthened hospital stays, more litigation, and even death. Existing methods and technology to address this problem mostly focus on stratifying inpatients at risk, without predicting fall severity or injuries. Here, a retrospective cohort study was designed and performed to predict the severity of inpatient falls, based on a machine learning classifier integrating multi-view ensemble learning and model-based missing data imputation method. As input, over two thousand inpatient fall patients' demographic characteristics, diagnoses, procedural data, and bone density measurements were retrieved from the HMH clinical data warehouse from two separate time periods. The predictive classifier developed based on multi-view ensemble learning with missing values (MELMV) outperformed other three baseline models; achieved a cross-validated AUC of 0.713 (95% CI, 0.701-0.725), an AUC of 0.808 (95% CI, 0.740-0.876) on the separate testing set. Our studies show the efficacy of integrative machine-learning based classifier model in dealing with multi-source patient data, which in this case delivers robust predictive performance on the severity of patient falls. The severe fall index provided by the MELMV classifier is calculated to identify inpatients who are at risk of having severe injuries if they fall, thus triggering additional steps of intervention to prevent a harmful fall, beyond the standard-of-care procedure for all high-risk fall patients.

A Deep Learning-Based Decision Support Tool for Precision Risk Assessment of Breast Cancer.

PURPOSE: The Breast Imaging Reporting and Data System (BI-RADS) lexicon was developed to standardize mammographic reporting to assess cancer risk and facilitate the decision to biopsy. Because of substantial interobserver variability in the application of the BI-RADS lexicon, the decision to biopsy varies greatly and results in overdiagnosis and excessive biopsies. The false-positive rate from mammograms is estimated to be 7% to approximately 10% overall, but within the BI-RADS 4 category, it is greater than 70%. Therefore, we developed the Breast Cancer Risk Calculator (BRISK) to target a well-characterized and specific patient subgroup (BI-RADS 4) rather than a broad heterogeneous group in assessing breast cancer risk. METHODS: BRISK provides a novel precise risk assessment model to reduce overdiagnosis and unnecessary biopsies. It was developed by applying natural language processing and deep learning methods on 5,147 patient records archived in the Houston Methodist systemwide data warehouse from 2006 to May 2015, including imaging and pathology reports, mammographic images, and patient demographics. Key characteristics for BI-RADS 4 patients were collected and computed to output an index measure for biopsy recommendation that is clinically relevant and informative and improves upon the traditional BI-RADS 4 scores. RESULTS: For the validation set, we assessed data from 1,247 BI-RADS 4 patients, including mammographic images and medical reports. The BRISK model sensitivity to predict malignancy was 100%, whereas the specificity was 74%. The total accuracy of our implemented model in BRISK was 81%. Overall area under the curve was 0.93. CONCLUSION: BRISK for abnormal mammogram uses integrative artificial intelligence technology and has demonstrated high sensitivity in the prediction of malignancy. Prospective evaluation is under way and can lead to improvement in patient-physician engagement in making informed decisions with regard to biopsy.