MASiVEdb: the Sirevirus Plant Retrotransposon Database

<p>Abstract</p> <p>Background</p> <p>Sireviruses are an ancient genus of the <it>Copia</it> superfamily of LTR retrotransposons, and the only one that has exclusively proliferated within plant genomes. Based on experimental data and phylogenetic analyses, Sireviruses have successfully infiltrated many branches of the plant kingdom, extensively colonizing the genomes of grass species. Notably, it was recently shown that they have been a major force in the make-up and evolution of the maize genome, where they currently occupy ~21% of the nuclear content and ~90% of the <it>Copia</it> population. It is highly likely, therefore, that their life dynamics have been fundamental in the genome composition and organization of a plethora of plant hosts. To assist studies into their impact on plant genome evolution and also facilitate accurate identification and annotation of transposable elements in sequencing projects, we developed MASiVEdb (Mapping and Analysis of SireVirus Elements Database), a collective and systematic resource of Sireviruses in plants.</p> <p>Description</p> <p>Taking advantage of the increasing availability of plant genomic sequences, and using an updated version of MASiVE, an algorithm specifically designed to identify Sireviruses based on their highly conserved genome structure, we populated MASiVEdb (<url>http://bat.infspire.org/databases/masivedb/</url>) with data on 16,243 intact Sireviruses (total length >158Mb) discovered in 11 fully-sequenced plant genomes. MASiVEdb is unlike any other transposable element database, providing a multitude of highly curated and detailed information on a specific genus across its hosts, such as complete set of coordinates, insertion age, and an analytical breakdown of the structure and gene complement of each element. All data are readily available through basic and advanced query interfaces, batch retrieval, and downloadable files. A purpose-built system is also offered for detecting and visualizing similarity between user sequences and Sireviruses, as well as for coding domain discovery and phylogenetic analysis.</p> <p>Conclusion</p> <p>MASiVEdb is currently the most comprehensive directory of Sireviruses, and as such complements other efforts in cataloguing plant transposable elements and elucidating their role in host genome evolution. Such insights will gradually deepen, as we plan to further improve MASiVEdb by phylogenetically mapping Sireviruses into families, by including data on fragments and solo LTRs, and by incorporating elements from newly-released genomes.</p

Tailored approaches grounded on immunogenetic features for refined prognostication in chronic lymphocytic leukemia

Chronic lymphocytic leukemia (CLL) patients with differential somatic hypermutation status of the immunoglobulin heavy variable genes, namely mutated or unmutated, display fundamental clinico-biological differences. Considering this, we assessed prognosis separately within mutated (M-CLL) and unmutated (U-CLL) CLL in 3015 patients, hypothesizing that the relative significance of relevant indicators may differ between these two categories. Within Binet A M-CLL patients, besides TP53 abnormalities, trisomy 12 and stereotyped subset #2 membership were equivalently associated with the shortest time-to first -treatment and a treatment probability at Five and ten years after diagnosis of 40% and 55%, respectively; the remaining cases exhibited 5-year and 10-year treatment probability of 12% and 25%, respectively. Within Binet A U-CLL patients, besides TP53 abnormalities, del(11q) and/or ST3B1 mutations were associated with the shortest time-to-First treatment (5- and 10-year treatment probability: 78% and 98%, respectively); in the remaining cases, males had a significantly worse prognosis than females. In conclusion, the relative weight of indicators that can accurately risk stratify early-stage CLL patients differs depending on the somatic hypermutation status of the immunoglobulin heavy variable genes of each patient. This finding highlights the fact that compartmentalized approaches based on immunogenetic features are necessary to refine and tailor prognostication in CLL

Tailored approaches grounded on immunogenetic features for refined prognostication in chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (CLL) patients with differentialsomatic hypermutation status of the immunoglobulin heavy vari-able genes, namely mutated or unmutated, display fundamentalclinico-biological differences. Considering this, we assessed prognosisseparately within mutated (M-CLL) and unmutated (U-CLL) CLL in 3015patients, hypothesizing that the relative significance of relevant indica-tors may differ between these two categories. Within Binet A M-CLLpatients, besides TP53abnormalities, trisomy 12 and stereotyped subset#2 membership were equivalently associated with the shortest time-to-first-treatment and a treatment probability at five and ten years afterdiagnosis of 40% and 55%, respectively; the remaining cases exhibited5-year and 10-year treatment probability of 12% and 25%, respectively.Within Binet A U-CLL patients, besides TP53abnormalities, del(11q)and/or SF3B1mutations were associated with the shortest time-to-first-treatment (5- and 10-year treatment probability: 78% and 98%, respec-tively); in the remaining cases, males had a significantly worse prognosisthan females. In conclusion, the relative weight of indicators that canaccurately risk stratify early-stage CLL patients differs depending on thesomatic hypermutation status of the immunoglobulin heavy variablegenes of each patient. This finding highlights the fact that compartmen-talized approaches based on immunogenetic features are necessary torefine and tailor prognostication in CLL