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Biomedical subjects

Laura E Brown

Publications and source records attributed to Laura E Brown.

2 recordsLinked to original sources

A novel algorithm for scalable and accurate Bayesian network learning.

Bayesian Networks (BN) is a knowledge representation formalism that has been proven to be valuable in biomedicine for constructing decision support systems and for generating causal hypotheses from data. Given the emergence of datasets in medicine and biology with thousands of variables and that current algorithms do not scale more than a few hundred variables in practical domains, new efficient and accurate algorithms are needed to learn high quality BNs from data. We present a new algorithm called Max-Min Hill-Climbing (MMHC) that builds upon and improves the Sparse Candidate (SC) algorithm; a state-of-the-art algorithm that scales up to datasets involving hundreds of variables provided the generating networks are sparse. Compared to the SC, on a number of datasets from medicine and biology, (a) MMHC discovers BNs that are structurally closer to the data-generating BN, (b) the discovered networks are more probable given the data, (c) MMHC is computationally more efficient and scalable than SC, and (d) the generating networks are not required to be uniformly sparse nor is the user of MMHC required to guess correctly the network connectivity

Algorithms↗

Comparison of mechanisms of anemia in mice with sickle cell disease and beta-thalassemia: peripheral destruction, ineffective erythropoiesis, and phospholipid scramblase-mediated phosphatidylserine exposure.

OBJECTIVES: 1). To study the mechanisms of anemia, erythroid hyperplasia, and red blood cell (RBC) clearance in murine models of sickle cell disease (Sickle) and beta-thalassemia (Th1/Th1); 2) To determine the contribution of the phospholipid scramblase enzyme to phosphatidylserine (PS) exposure and RBC death in Sickle and Th1/Th1 mice. METHODS: We used a combination of flow-cytometric analysis and assays for phospholipid remodeling to determine the extent and sites of erythroid hyperplasia, PS exposure, and cell death. RESULTS: 1) Sickle RBCs have a much shorter half-life than Th1/Th1 RBCs (0.8 days vs. 11 days). A significant proportion of Th1/Th1 peripheral reticulocytes mature into erythrocytes, however, approximately fivefold fewer Sickle reticulocytes mature. While erythroid hyperplasia exists in both Sickle and Th1/Th1 mice, Th1/Th1 produce fourfold more RBCs than necessary to maintain steady state, while Sickle produce no excess RBCs. 2) 61% of Sickle and 34% of Th1/Th1 RBCs are scramblase(+) as measured by internalization assays of the fluorescent phospholipid NBD-PC. The majority of NBD-PC(+) RBCs are also annexin-V(+), supporting a mechanistic link between scramblase activity and PS exposure. A proportion of both reticulocytes and older RBCs in Sickle and Th1/Th1 mice have active scramblase, and the degree of scramblase activation in these strains correlates with the propensity for RBC death. CONCLUSIONS: Sickle and Th1/Th1 mice are both anemic, with significant erythroid hyperplasia. Th1/Th1 mice display ineffective erythropoiesis while Sickle mice show rapid peripheral destruction of RBCs. PS exposure and phospholipid scramblase activity serve as markers of RBCs with altered phospholipid asymmetry and greater propensity for cell death.

Anemia, Sickle Cell↗