Biology subjects

Alcala, N.

Publications and source records attributed to Alcala, N..

3 recordsLinked to original sources

bioRxiv2018

Redefining mesothelioma types as a continuum uncovers the immune and vascular systems as key players in the diagnosis and prognosis of this disease

Malignant Pleural Mesothelioma (MPM) is an aggressive disease related to asbestos exposure, which incidence is expected to increase in the future, and with no effective therapeutic options. We have performed unsupervised analyses of publicly available RNAseq data for 297 MPM. We found that the molecular profile and the prognosis of this disease is better explained by a continuous model rather than by the current WHO classification into the epitheloid, biphasic and sarcomatoid histological types. The main source of variation of this continuum was explained by the immune and vascular pathways, with strong differences in the expression of pro-angiogenic genes and immune checkpoint inhibitors across samples. These data may inform future classifications of MPM and may also guide personalised therapeutic approaches for this disease.\n\nSignificanceMalignant Pleural Mesothelioma (MPM) is an aggressive disease with no effective therapeutic options. Unsupervised transcriptomic analyses of 297 MPM unveiled the vascular and the immune systems as key players in the prognosis of this disease, and identified potential therapeutic approaches for this disease targeting these pathways.

cancer biology↗

bioRxiv2017

Coalescent theory of migration network motifs

Natural populations display a variety of spatial arrangements, each potentially with a distinctive impact on genetic diversity and genetic differentiation among subpopulations. Although the spatial arrangement of populations can lead to intricate migration networks, theoretical developments have focused mainly on a small subset of such networks, emphasizing the island-migration and stepping-stone models. In this study, we investigate all small network motifs: the set of all possible migration networks among populations subdivided into at most four subpopulations. For each motif, we use coalescent theory to derive expectations for three quantities that describe genetic variation: nucleotide diversity, FST, and half-time to equilibrium diversity. We describe the impact of network properties on these quantities, finding that motifs with a large mean node degree have the largest nucleotide diversity and the longest time to equilibrium, whereas motifs with small density have the largest FST. In addition, we show that the motifs whose pattern of variation is most strongly influenced by loss of a connection or a subpopulation are those that can be split easily into several disconnected components. We illustrate our results using two example datasets--sky island birds of genus Brachypteryx and Indian tigers--identifying disturbance scenarios that produce the greatest reduction in genetic diversity; for tigers, we also compare the benefits of two assisted gene flow scenarios. Our results have consequences for understanding the effect of geography on genetic diversity and for designing strategies to alter population migration networks to maximize genetic variation in the context of conservation of endangered species.

genetics↗

bioRxiv2016

Mathematical constraints on FST: biallelic markers in arbitrarily many populations

FST is one of the most widely used statistics in population genetics. Recent mathematical studies have identified constraints on FST that challenge interpretations of FST as a measure with potential to range from 0 for genetically similar populations to 1 for divergent populations. We generalize results obtained for population pairs to arbitrarily many populations, characterizing the mathematical relationship between FST, the frequency M of the more frequent allele at a polymorphic biallelic marker, and the number of subpopulations K. We show that for fixed K, FST has a peculiar constraint as a function of M, with a maximum of 1 only if M = i/K for integers i with {lceil}K/2{rciel} [≤] i [≤] K - 1. For fixed M, as K grows large, the range of FST becomes the full closed or half-open unit interval. For fixed K, however, some M < (K - 1)/K always exists at which the upper bound on FST is constrained to be below [Formula]. In each of three migration models--island, rectangular stepping-stone, and linear stepping-stone--we use coalescent simulations to show that under weak migration, FST depends strongly on the allele frequency M when K is small, but not when K is large. Finally, using data on human genetic variation, we employ our results to explain the generally smaller FST values between pairs of continents relative to global FST values. We discuss implications for the interpretation and use of FST.

genetics↗