Search Results (6)

Integer linear programs (ILPs) and mixed integer programs (MIPs) often have multiple distinct optimal solutions, yet the widely used Gurobi optimization solver returns certain solutions at disproportionately high frequencies. This behavior is disadvantageous, as, in fields such as biomedicine, the identification and analysis of distinct optima yields valuable domain-specific insights that inform future research directions. In the present work, we introduce MORSE (Multiple Optima via Random Sampling and careful choice of the parameter Epsilon), a randomized, parallelizable algorithm to efficiently generate multiple optima for ILPs. MORSE maps multiplicative perturbations to the coefficients in an instance’s objective function, generating a modified instance that retains an optimum of the original problem. We formalize and prove the above claim in some practical conditions. Furthermore, we prove that for 0/1 selection problems, MORSE finds each distinct optimum with equal probability. We evaluate MORSE using two measures; the number of distinct optima found in r independent runs, and the diversity of the list (with repetitions) of solutions by average pairwise Hamming distance and Shannon entropy. Using these metrics, we provide empirical results demonstrating that MORSE outperforms the Gurobi method and unweighted variations of the MORSE method on a set of 20 Mixed Integer Programming Library (MIPLIB) instances and on a combinatorial optimization problem in cancer genomics. Full article

Chimeric antigen receptor (CAR) T cell therapies have yielded transformative clinical successes for patients with blood tumors, but their full potential remains to be unleashed against solid tumors. One challenge is finding selective targets, which we define intuitively to be cell surface proteins that are expressed widely by cancer cells but minimally by healthy cells in the tumor microenvironment and other normal tissues. Analyzing patient tumor single-cell transcriptomics data, we first defined and quantified selectivity and safety scores of existing CAR targets for indications in which they are in clinical trials or approved. We then sought new candidate cell surface CAR targets that have better selectivity and safety scores than those currently being tested. Remarkably, in almost all cancer types, we could not find such better targets, testifying to the near optimality of the current target space. However, in human papillomavirus (HPV)-negative head and neck squamous cell carcinoma (HNSC), for which there is currently a dearth of existing CAR targets, we identified a total of twenty candidate novel CAR targets, five of which have both superior selectivity and safety scores. These newly identified cell surface targets lay a basis for future investigations that may lead to better CAR treatments in HNSC. Full article

Cancer occurs more frequently in men while autoimmune diseases (AIDs) occur more frequently in women. To explore whether these sex biases have a common basis, we collected 167 AID incidence studies from many countries for tissues that have both a cancer type and an AID that arise from that tissue. Analyzing a total of 182 country-specific, tissue-matched cancer-AID incidence rate sex bias data pairs, we find that, indeed, the sex biases observed in the incidence of AIDs and cancers that occur in the same tissue are positively correlated across human tissues. The common key factor whose levels across human tissues are most strongly associated with these incidence rate sex biases is the sex bias in the expression of the 37 genes encoded in the mitochondrial genome. Full article

Vaccines have allowed for a significant decrease in COVID-19 risk, and new antiviral medications can prevent disease progression if given early in the course of the disease. The rapid and accurate estimation of the risk of severe disease in new patients is needed to prioritize the treatment of high-risk patients and maximize lives saved. We used electronic health records from 101,039 individuals infected with SARS-CoV-2, since the beginning of the pandemic and until 30 November 2021, in a national healthcare organization in Israel to build logistic models estimating the probability of subsequent hospitalization and death of newly infected patients based on a few major risk factors (age, sex, body mass index, hemoglobin A1C, kidney function, and the presence of hypertension, pulmonary disease, and malignancy) and the number of BNT162b2 mRNA vaccine doses received. The model’s performance was assessed by 10-fold cross-validation: the area under the curve was 0.889 for predicting hospitalization and 0.967 for predicting mortality. A total of 50%, 80%, and 90% of death events could be predicted with respective specificities of 98.6%, 95.2%, and 91.2%. These models enable the rapid identification of individuals at high risk for hospitalization and death when infected, and they can be used to prioritize patients to receive scarce medications or booster vaccination. The calculator is available online. Full article

Background: Immune protection following either vaccination or infection with SARS-CoV-2 decreases over time. Objective: We aim to describe clinical and sociodemographic characteristics associated with COVID-19 infection at least 14 days after booster vaccination in the Israeli population. Methods: We conducted a population-based study among adult members of Leumit Health Services (LHS) in Israel. Nasopharyngeal swabs were examined for SARS-CoV-2 by real-time RT-PCR. The hematological and biochemical parameters in the peripheral blood before booster vaccination were evaluated. Results: Between 1 February 2021 and 30 November 2021, 136,683 individuals in LHS were vaccinated with a booster (third dose) of the BNT162b2 vaccine. Of these, 1171 (0.9%) were diagnosed with COVID-19 by testing positive for SARS-CoV-2 RT-PCR at least >14 days after the booster vaccination. The COVID-19-positive group was characterized by higher rates of chronic kidney disease than the matched COVID-19-negative group (43 (3.7%) vs. 3646 (2.7%); p = 0.039). Anemia, lower peripheral blood lymphocytes, monocytes, basophils, C3 Complement, cholesterol, and prothrombin time were also associated with COVID-19 after booster vaccination. Conclusion: People with chronic kidney disease and anemia should be included in possible future annual SARS-CoV-2 vaccination recommendations. Full article

Immune protection following either vaccination or infection with SARS-CoV-2 is thought to decrease over time. We designed a retrospective study, conducted at Leumit Health Services in Israel, to determine the kinetics of SARS-CoV-2 IgG antibodies following administration of two doses of BNT162b2 vaccine, or SARS-CoV-2 infection in unvaccinated individuals. Antibody titers were measured between 31 January 2021, and 31 July 2021 in two mutually exclusive groups: (i) vaccinated individuals who received two doses of BNT162b2 vaccine and had no history of previous infection with COVID-19 and (ii) SARS-CoV-2 convalescents who had not received the vaccine. A total of 2653 individuals fully vaccinated by two doses of vaccine during the study period and 4361 convalescent patients were included. Higher SARS-CoV-2 IgG antibody titers were observed in vaccinated individuals (median 1581 AU/mL IQR [533.8–5644.6]) after the second vaccination than in convalescent individuals (median 355.3 AU/mL IQR [141.2–998.7]; p < 0.001). In vaccinated subjects, antibody titers decreased by up to 38% each subsequent month while in convalescents they decreased by less than 5% per month. Six months after BNT162b2 vaccination 16.1% subjects had antibody levels below the seropositivity threshold of <50 AU/mL, while only 10.8% of convalescent patients were below <50 AU/mL threshold after 9 months from SARS-CoV-2 infection. This study demonstrates individuals who received the Pfizer-BioNTech mRNA vaccine have different kinetics of antibody levels compared to patients who had been infected with the SARS-CoV-2 virus, with higher initial levels but a much faster exponential decrease in the first group. Full article