Paola Sebastiani

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Paola Sebastiani is a biostatistician and a professor at Boston University working in the field of genetic epidemiology, building prognostic models that can be used for the dissection of complex traits. Her research interests include Bayesian modeling of biomedical data, particularly genetic and genomic data.

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Education and career

Sebastiani obtained a first degree in mathematics from the University of Perugia, Italy (1987), an M.Sc. in statistics from University College London (1990), and a Ph.D. in statistics from the Sapienza University of Rome (1992). She came to Boston University in 2003, after previously having been an assistant professor in the Department of Mathematics and Statistics at the University of Massachusetts Amherst. [1]

Contributions

Her most important contribution is a model based on a Bayesian network that integrates more than 60 single-nucleotide polymorphisms (SNPs) and other biomarkers to compute the risk for stroke in patients with sickle cell anemia. This model was shown to have high sensitivity and specificity and demonstrated, for the first time, how an accurate risk prediction model of a complex genetic trait that is modulated by several interacting genes can be built using Bayesian networks. [2]

A controversial paper regarding the genetics of aging with which she was associated was retracted from the journal Science in 2011 due to flawed data. [3] [4] The corrected version was published in PLOS ONE, [5] and several of the genes found associated with exceptional human longevity were replicated in other studies of centenarians. [6] [7] [8] [9]

Publications

She has published several peer-reviewed papers. According to Scopus the most cited ones are:

Awards and honors

She became a fellow of the American Statistical Association in 2017. [10]

Related Research Articles

Genetic disorder Health problem caused by one or more abnormalities in the genome

A genetic disorder is a health problem caused by one or more abnormalities in the genome. It can be caused by a mutation in a single gene (monogenic) or multiple genes (polygenic) or by a chromosomal abnormality. Although polygenic disorders are the most common, the term is mostly used when discussing disorders with a single genetic cause, either in a gene or chromosome. The mutation responsible can occur spontaneously before embryonic development, or it can be inherited from two parents who are carriers of a faulty gene or from a parent with the disorder. Some disorders are caused by a mutation on the X chromosome and have X-linked inheritance. Very few disorders are inherited on the Y chromosome or mitochondrial DNA.

Single-nucleotide polymorphism Single nucleotide position in genomic DNA at which different sequence alternatives exist

A single-nucleotide polymorphism is a substitution of a single nucleotide at a specific position in the genome, that is present in a sufficiently large fraction of the population.

Fetal hemoglobin

Fetal hemoglobin, or foetal haemoglobin is the main oxygen carrier protein in the human fetus. Hemoglobin F is found in fetal red blood cells, and is involved in transporting oxygen from the mother's bloodstream to organs and tissues in the fetus. It is produced at around 6 weeks of pregnancy and the levels remain high after birth until the baby is roughly 2–4 months old. Hemoglobin F has a different composition from the adult forms of hemoglobin, which allows it to bind oxygen more strongly. This way, the developing fetus is able to retrieve oxygen from the mother's bloodstream, which occurs through the placenta found in the mother's uterus.

Point mutation Replacement, insertion, or deletion of a single DNA or RNA nucleotide

A point mutation or substitution is a genetic mutation where a single nucleotide base is changed, inserted or deleted from a DNA or RNA sequence of an organism's genome. Point mutations have a variety of effects on the downstream protein product—consequences that are moderately predictable based upon the specifics of the mutation. These consequences can range from no effect to deleterious effects, with regard to protein production, composition, and function.

Pleiotropy Influence of a single gene on multiple phenotypic traits

Pleiotropy occurs when one gene influences two or more seemingly unrelated phenotypic traits. Such a gene that exhibits multiple phenotypic expression is called a pleiotropic gene. Mutation in a pleiotropic gene may have an effect on several traits simultaneously, due to the gene coding for a product used by a myriad of cells or different targets that have the same signaling function.

Hemoglobin c is an abnormal hemoglobin in which glutamic acid residue at the 6th position of the β-globin chain is replaced with a lysine residue due to a point mutation in the HBB gene. It produces sickle cell trait but not the disease, as it causes only mild sickling of the RBCs. Thus, it is the least dangerous among sickle cell trait-producing hemoglobins such as HbS and HbO.

Diamond–Blackfan anemia (DBA) is a congenital erythroid aplasia that usually presents in infancy. DBA causes low red blood cell counts (anemia), without substantially affecting the other blood components, which are usually normal. This is in contrast to Shwachman–Bodian–Diamond syndrome, in which the bone marrow defect results primarily in neutropenia, and Fanconi anemia, where all cell lines are affected resulting in pancytopenia.

Multifactor dimensionality reduction (MDR) is a statistical approach, also used in machine learning automatic approaches, for detecting and characterizing combinations of attributes or independent variables that interact to influence a dependent or class variable. MDR was designed specifically to identify nonadditive interactions among discrete variables that influence a binary outcome and is considered a nonparametric and model-free alternative to traditional statistical methods such as logistic regression.

5-lipoxygenase-activating protein

Arachidonate 5-lipoxygenase-activating protein also known as 5-lipoxygenase activating protein, or FLAP, is a protein that in humans is encoded by the ALOX5AP gene.

Thiamine transporter 1

Thiamine transporter 1, also known as thiamine carrier 1 (TC1) or solute carrier family 19 member 2 (SLC19A2) is a protein that in humans is encoded by the SLC19A2 gene. SLC19A2 is a thiamine transporter. Mutations in this gene cause thiamine-responsive megaloblastic anemia syndrome (TRMA), which is an autosomal recessive disorder characterized by diabetes mellitus, megaloblastic anemia and sensorineural deafness.

Genome-wide association study Study to research genome-wide set of genetic variants in different individuals to see if any variant is associated with a trait.

In genetics, a genome-wide association study, also known as whole genome association study, is an observational study of a genome-wide set of genetic variants in different individuals to see if any variant is associated with a trait. GWASs typically focus on associations between single-nucleotide polymorphisms (SNPs) and traits like major human diseases, but can equally be applied to any other genetic variants and any other organisms.

OR7D4

Olfactory receptor 7D4 is a protein that in humans is encoded by the OR7D4 gene.

TOX

Thymocyte selection-associated high mobility group box protein TOX is a protein that in humans is encoded by the TOX gene.

Sickle cell disease Group of genetic blood disorders

Sickle cell disease (SCD) is a group of blood disorders typically inherited from a person's parents. The most common type is known as sickle cell anaemia (SCA). It results in an abnormality in the oxygen-carrying protein haemoglobin found in red blood cells. This leads to a rigid, sickle-like shape under certain circumstances. Problems in sickle cell disease typically begin around 5 to 6 months of age. A number of health problems may develop, such as attacks of pain, anemia, swelling in the hands and feet, bacterial infections and stroke. Long-term pain may develop as people get older. The average life expectancy in the developed world is 40 to 60 years.

Just another Gibbs sampler (JAGS) is a program for simulation from Bayesian hierarchical models using Markov chain Monte Carlo (MCMC), developed by Martyn Plummer. JAGS has been employed for statistical work in many fields, for example ecology, management, and genetics.

Steven E. Brenner

Steven Elliot Brenner is a professor at the Department of Plant and Microbial Biology at the University of California Berkeley, Adjunct Professor at the Department of Bioengineering and Therapeutic Sciences at the University of California, and San Francisco Faculty Scientist, Physical Biosciences at the Lawrence Berkeley National Laboratory.

In molecular biology mir-71 microRNA is a short RNA molecule. MicroRNAs function to regulate the expression levels of other genes by several mechanisms.

Viral phylodynamics is defined as the study of how epidemiological, immunological, and evolutionary processes act and potentially interact to shape viral phylogenies. Since the coining of the term in 2004, research on viral phylodynamics has focused on transmission dynamics in an effort to shed light on how these dynamics impact viral genetic variation. Transmission dynamics can be considered at the level of cells within an infected host, individual hosts within a population, or entire populations of hosts.

Hemoglobin Hopkins-2

Hemoglobin Hopkins-2 is a mutation of the protein hemoglobin, which is responsible for the transportation of oxygen through the blood from the lungs to the musculature of the body in vertebrates. The specific mutation in Hemoglobin Hopkins-2 results in two abnormal α chains. The mutation is the result of histidine 112 being replaced with aspartic acid in the protein's polypeptide sequence. Additionally, within one of the mutated alpha chains, there are substitutes at 114 and 118, two points on the amino acid chain. This mutation can cause sickle cell anemia.

The disposable soma theory of aging states that organisms age due to an evolutionary trade-off between growth, reproduction, and DNA repair maintenance. Formulated by Thomas Kirkwood, the disposable soma theory explains that an organism only has a limited amount of resources or "soma" that it can allocate to its various cellular processes. Therefore, a greater investment in growth and reproduction would result in reduced investment in DNA repair maintenance, leading to increased cellular damage, shortened telomeres, accumulation of mutations, compromised stem cells, and ultimately, senescence. Although many models, both animal and human, have appeared to support this theory, parts of it are still controversial. Specifically, while the evolutionary trade-off between growth and aging has been well established, the relationship between reproduction and aging is still without scientific consensus, and the cellular mechanisms largely undiscovered.

References

  1. ↑ "BU Homepage for Paola Sebastiani" . Retrieved 2009-02-03.
  2. ↑ Sebastiani P, Ramoni MF, Nolan V, Baldwin CT, Steinberg MH (April 2005). "Genetic dissection and prognostic modeling of overt stroke in sickle cell anemia". Nature Genetics . 37 (4): 435–40. doi:10.1038/ng1533. PMC   2896308 . PMID   15778708.
  3. ↑ Wade, Nicholas (22 July 2011). "Scientists Retract Report on Predicting Longevity". The New York Times.
  4. ↑ "Science Longevity Paper Rectracted". July 2011. Archived from the original on 2013-03-17. Retrieved 2013-03-11.
  5. ↑ Sebastiani, Paola; Solovieff, Nadia; Dewan, Andrew T.; Walsh, Kyle M.; Puca, Annibale; Hartley, Stephen W.; Melista, Efthymia; Andersen, Stacy; Dworkis, Daniel A.; Wilk, Jemma B.; Myers, Richard H.; Steinberg, Martin H.; Montano, Monty; Baldwin, Clinton T.; Hoh, Josephine; Perls, Thomas T. (2012). "Genetic Signatures of Exceptional Longevity in Humans". PLOS ONE. 7 (1): e29848. Bibcode:2012PLoSO...729848S. doi:10.1371/journal.pone.0029848. PMC   3261167 . PMID   22279548.
  6. ↑ Conneely, Karen N.; Capell, Brian C.; Erdos, Michael R.; Sebastiani, Paola; Solovieff, Nadia; Swift, Amy J.; Baldwin, Clinton T.; Budagov, Temuri; Barzilai, Nir; Atzmon, Gil; Puca, Annibale A.; Perls, Thomas T.; Geesaman, Bard J.; Boehnke, Michael; Collins, Francis S. (2012). "Human longevity and common variations in the LMNA gene: a meta-analysis". Aging Cell. 11 (3): 475–481. doi:10.1111/j.1474-9726.2012.00808.x. PMC   3350595 . PMID   22340368.
  7. ↑ Lu F, Guan H, Gong B, Liu X, Zhu R, Wang Y, Qian J, Zhou T, Lan X, Wang P, Lin Y, Ma S, Lin H, Zhu X, Chen R, Zhu X, Shi Y, Yang Z (2014). "Genetic Variants in PVRL2-TOMM40-APOE Region Are Associated with Human Longevity in a Han Chinese Population". PLOS ONE. 9 (6): e99580. Bibcode:2014PLoSO...999580L. doi:10.1371/journal.pone.0099580. PMC   4055715 . PMID   24924924.
  8. ↑ Tomàs Pinós (2014). "The rs1333049 polymorphism on locus 9p21.3 and extreme longevity in Spanish and Japanese cohorts". AGE. 36 (2): 933–943. doi:10.1007/s11357-013-9593-0. PMC   4039251 . PMID   24163049.
  9. ↑ Sebastiani P, Bae H, Sun FX, Andersen SL, Daw EW, Malovini A, Kojima T, Hirose N, Schupf N, Puca A, Perls TT (2013). "Meta-analysis of genetic variants associated with human exceptional longevity". Aging. 5 (9): 653–61. doi:10.18632/aging.100594. PMC   3808698 . PMID   24244950.
  10. ↑ "ASA Fellows list". American Statistical Association. Archived from the original on 2017-12-01. Retrieved 2017-11-02.
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