Cell Population Growth Kinetics in the Presence of Stochastic Heterogeneity of Cell Phenotype

Recent studies at individual cell resolution have revealed phenotypic heterogeneity in nominally clonal tumor cell populations. The heterogeneity affects cell growth behaviors, which can result in departure from the idealized uniform exponential growth of the cell population. Here we measured the stochastic time courses of growth of an ensemble of populations of HL60 leukemia cells in cultures, starting with distinct initial cell numbers to capture a departure from the {uniform exponential growth model for the initial growth (``take-off'')}. Despite being derived from the same cell clone, we observed significant variations in the early growth patterns of individual cultures with statistically significant differences in growth dynamics, which could be explained by the presence of inter-converting subpopulations with different growth rates, and which could last for many generations. Based on the hypothesis of existence of multiple subpopulations, we developed a branching process model that was consistent with the experimental observations

An approach for collaborative development of a federated biomedical knowledge graph-based question-answering system: Question-of-the-Month challenges

Knowledge graphs have become a common approach for knowledge representation. Yet, the application of graph methodology is elusive due to the sheer number and complexity of knowledge sources. In addition, semantic incompatibilities hinder efforts to harmonize and integrate across these diverse sources. As part of The Biomedical Translator Consortium, we have developed a knowledge graph-based question-answering system designed to augment human reasoning and accelerate translational scientific discovery: the Translator system. We have applied the Translator system to answer biomedical questions in the context of a broad array of diseases and syndromes, including Fanconi anemia, primary ciliary dyskinesia, multiple sclerosis, and others. A variety of collaborative approaches have been used to research and develop the Translator system. One recent approach involved the establishment of a monthly "Question-of-the-Month (QotM) Challenge" series. Herein, we describe the structure of the QotM Challenge; the six challenges that have been conducted to date on drug-induced liver injury, cannabidiol toxicity, coronavirus infection, diabetes, psoriatic arthritis, and ATP1A3-related phenotypes; the scientific insights that have been gleaned during the challenges; and the technical issues that were identified over the course of the challenges and that can now be addressed to foster further development of the prototype Translator system. We close with a discussion on Large Language Models such as ChatGPT and highlight differences between those models and the Translator system

SOX2 is an amplified lineage-survival oncogene in lung and esophageal squamous cell carcinomas

Lineage survival oncogenes are activated by somatic DNA alterations in cancers arising from the cell lineages in which these genes play a role in normal development.1,2 Here we show that a peak of genomic amplification on chromosome 3q26.33, found in squamous cell carcinomas (SCCs) of the lung and esophagus, contains the transcription factor gene SOX2—which is mutated in hereditary human esophageal malformations3 and necessary for normal esophageal squamous development4, promotes differentiation and proliferation of basal tracheal cells5 and co-operates in induction of pluripotent stem cells.6,7,8 SOX2 expression is required for proliferation and anchorage-independent growth of lung and esophageal cell lines, as shown by RNA interference experiments. Furthermore, ectopic expression of SOX2 cooperated with FOXE1 or FGFR2 to transform immortalized tracheobronchial epithelial cells. SOX2-driven tumors show expression of markers of both squamous differentiation and pluripotency. These observations identify SOX2 as a novel lineage survival oncogene in lung and esophageal SCC

Opportunities and Challenges in Interpreting and Sharing Personal Genomes

The 2019 “Personal Genomes: Accessing, Sharing and Interpretation” conference (Hinxton, UK, 11–12 April 2019) brought together geneticists, bioinformaticians, clinicians and ethicists to promote openness and ethical sharing of personal genome data while protecting the privacy of individuals. The talks at the conference focused on two main topic areas: (1) Technologies and Applications, with emphasis on personal genomics in the context of healthcare. The issues discussed ranged from new technologies impacting and enabling the field, to the interpretation of personal genomes and their integration with other data types. There was particular emphasis and wide discussion on the use of polygenic risk scores to inform precision medicine. (2) Ethical, Legal, and Social Implications, with emphasis on genetic privacy: How to maintain it, how much privacy is possible, and how much privacy do people want? Talks covered the full range of genomic data visibility, from open access to tight control, and diverse aspects of balancing benefits and risks, data ownership, working with individuals and with populations, and promoting citizen science. Both topic areas were illustrated and informed by reports from a wide variety of ongoing projects, which highlighted the need to diversify global databases by increasing representation of understudied populations.</jats:p

Opportunities and Challenges in Interpreting and Sharing Personal Genomes.

The 2019 Personal Genomes: Accessing, Sharing and Interpretation conference (Hinxton, UK, 11-12 April 2019) brought together geneticists, bioinformaticians, clinicians and ethicists to promote openness and ethical sharing of personal genome data while protecting the privacy of individuals. The talks at the conference focused on two main topic areas: (1) Technologies and Applications, with emphasis on personal genomics in the context of healthcare. The issues discussed ranged from new technologies impacting and enabling the field, to the interpretation of personal genomes and their integration with other data types. There was particular emphasis and wide discussion on the use of polygenic risk scores to inform precision medicine. (2) Ethical, Legal, and Social Implications, with emphasis on genetic privacy: How to maintain it, how much privacy is possible, and how much privacy do people want? Talks covered the full range of genomic data visibility, from open access to tight control, and diverse aspects of balancing benefits and risks, data ownership, working with individuals and with populations, and promoting citizen science. Both topic areas were illustrated and informed by reports from a wide variety of ongoing projects, which highlighted the need to diversify global databases by increasing representation of understudied populations

Opportunities and Challenges in Interpreting and Sharing Personal Genomes

The 2019 &ldquo;Personal Genomes: Accessing, Sharing and Interpretation&rdquo; conference (Hinxton, UK, 11&ndash;12 April 2019) brought together geneticists, bioinformaticians, clinicians and ethicists to promote openness and ethical sharing of personal genome data while protecting the privacy of individuals. The talks at the conference focused on two main topic areas: (1) Technologies and Applications, with emphasis on personal genomics in the context of healthcare. The issues discussed ranged from new technologies impacting and enabling the field, to the interpretation of personal genomes and their integration with other data types. There was particular emphasis and wide discussion on the use of polygenic risk scores to inform precision medicine. (2) Ethical, Legal, and Social Implications, with emphasis on genetic privacy: How to maintain it, how much privacy is possible, and how much privacy do people want? Talks covered the full range of genomic data visibility, from open access to tight control, and diverse aspects of balancing benefits and risks, data ownership, working with individuals and with populations, and promoting citizen science. Both topic areas were illustrated and informed by reports from a wide variety of ongoing projects, which highlighted the need to diversify global databases by increasing representation of understudied populations