With DNA sequencing now getting cheaper more quickly than data storage or computation, the time may have come for genome informatics to migrate to the cloud.
Quantitative criteria for species delimitation TOBIAS, JOSEPH A.; SEDDON, NATHALIE; SPOTTISWOODE, CLAIRE N. ...
Ibis (London, England),
October 2010, Letnik:
152, Številka:
4
Journal Article
Recenzirano
Species are the fundamental units of biology, ecology and conservation, and progress in these fields is therefore hampered by widespread taxonomic bias and uncertainty. Numerous operational ...techniques based on molecular or phenotypic data have been designed to overcome this problem, yet existing procedures remain subjective or inconsistent, particularly when applying the biological species concept. We address this issue by developing quantitative methods for a classic technique in systematic zoology, namely the use of divergence between undisputed sympatric species as a yardstick for assessing the taxonomic status of allopatric forms. We calculated mean levels of differentiation in multiple phenotypic characters – including biometrics, plumage and voice – for 58 sympatric or parapatric species‐pairs from 29 avian families. We then used estimates of mean divergence to develop criteria for species delimitation based on data‐driven thresholds. Preliminary tests show that these criteria result in relatively few changes to avian taxonomy in Europe, yet are capable of extensive reassignment of species limits in poorly known tropical regions. While we recognize that species limits are in many cases inherently arbitrary, we argue that our system can be applied to the global avifauna to deliver taxonomic decisions with a high level of objectivity, consistency and transparency.
In a classical view of hematopoiesis, the various blood cell lineages arise via a hierarchical scheme starting with multipotent stem cells that become increasingly restricted in their differentiation ...potential through oligopotent and then unipotent progenitors. We developed a cell-sorting scheme to resolve myeloid (My), erythroid (Er), and megakaryocytic (Mk) fates from single CD34(+) cells and then mapped the progenitor hierarchy across human development. Fetal liver contained large numbers of distinct oligopotent progenitors with intermingled My, Er, and Mk fates. However, few oligopotent progenitor intermediates were present in the adult bone marrow. Instead, only two progenitor classes predominate, multipotent and unipotent, with Er-Mk lineages emerging from multipotent cells. The developmental shift to an adult "two-tier" hierarchy challenges current dogma and provides a revised framework to understand normal and disease states of human hematopoiesis.
Intra-tumor heterogeneity (ITH) is a mechanism of therapeutic resistance and therefore an important clinical challenge. However, the extent, origin, and drivers of ITH across cancer types are poorly ...understood. To address this, we extensively characterize ITH across whole-genome sequences of 2,658 cancer samples spanning 38 cancer types. Nearly all informative samples (95.1%) contain evidence of distinct subclonal expansions with frequent branching relationships between subclones. We observe positive selection of subclonal driver mutations across most cancer types and identify cancer type-specific subclonal patterns of driver gene mutations, fusions, structural variants, and copy number alterations as well as dynamic changes in mutational processes between subclonal expansions. Our results underline the importance of ITH and its drivers in tumor evolution and provide a pan-cancer resource of comprehensively annotated subclonal events from whole-genome sequencing data.
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•Pan-cancer resource of comprehensively annotated intra-tumor heterogeneity (ITH)•ITH is pervasive across cancers and shows cancer type-specific patterns•Branching phylogenies are common•Dynamic changes in mutational processes between subclonal expansions
Dentro et al. provide a comprehensive annotation of intra-tumor heterogeneity and its drivers in cancer evolution.
World governments have committed to halting human-induced extinctions and safeguarding important sites for biodiversity by 2020, but the financial costs of meeting these targets are largely unknown. ...We estimate the cost of reducing the extinction risk of all globally threatened bird species (by > 1 International Union for Conservation of Nature Red List category) to be U.S. $0.875 to $1.23 billion annually over the next decade, of which 12% is currently funded. Incorporating threatened nonavian species increases this total to U.S. $3.41 to $4.76 billion annually. We estimate that protecting and effectively managing all terrestrial sites of global avian conservation significance (11,731 Important Bird Areas) would cost U.S. $ 65.1 billion annually. Adding sites for other taxa increases this to U.S. $76.1 billion annually. Meeting these targets will require conservation funding to increase by at least an order of magnitude.
Cancers are caused by genomic alterations known as drivers. Hundreds of drivers in coding genes are known but, to date, only a handful of noncoding drivers have been discovered-despite intensive ...searching
. Attention has recently shifted to the role of altered RNA splicing in cancer; driver mutations that lead to transcriptome-wide aberrant splicing have been identified in multiple types of cancer, although these mutations have only been found in protein-coding splicing factors such as splicing factor 3b subunit 1 (SF3B1)
. By contrast, cancer-related alterations in the noncoding component of the spliceosome-a series of small nuclear RNAs (snRNAs)-have barely been studied, owing to the combined challenges of characterizing noncoding cancer drivers and the repetitive nature of snRNA genes
. Here we report a highly recurrent A>C somatic mutation at the third base of U1 snRNA in several types of tumour. The primary function of U1 snRNA is to recognize the 5' splice site via base-pairing. This mutation changes the preferential A-U base-pairing between U1 snRNA and the 5' splice site to C-G base-pairing, and thus creates novel splice junctions and alters the splicing pattern of multiple genes-including known drivers of cancer. Clinically, the A>C mutation is associated with heavy alcohol use in patients with hepatocellular carcinoma, and with the aggressive subtype of chronic lymphocytic leukaemia with unmutated immunoglobulin heavy-chain variable regions. The mutation in U1 snRNA also independently confers an adverse prognosis to patients with chronic lymphocytic leukaemia. Our study demonstrates a noncoding driver in spliceosomal RNAs, reveals a mechanism of aberrant splicing in cancer and may represent a new target for treatment. Our findings also suggest that driver discovery should be extended to a wider range of genomic regions.
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