Revealing mammalian evolutionary relationships by comparative analysis of gene clusters

Many software tools for comparative analysis of genomic sequence data have been released in recent decades. Despite this, it remains challenging to determine evolutionary relationships in gene clusters due to their complex histories involving duplications, deletions, inversions, and conversions. One concept describing these relationships is orthology. Orthologs derive from a common ancestor by speciation, in contrast to paralogs, which derive from duplication. Discriminating orthologs from paralogs is a necessary step in most multispecies sequence analyses, but doing so accurately is impeded by the occurrence of gene conversion events. We propose a refined method of orthology assignment based on two paradigms for interpreting its definition: by genomic context or by sequence content. X-orthology (based on context) traces orthology resulting from speciation and duplication only, while N-orthology (based on content) includes the influence of conversion events

PANTHER version 7: improved phylogenetic trees, orthologs and collaboration with the Gene Ontology Consortium

Protein Analysis THrough Evolutionary Relationships (PANTHER) is a comprehensive software system for inferring the functions of genes based on their evolutionary relationships. Phylogenetic trees of gene families form the basis for PANTHER and these trees are annotated with ontology terms describing the evolution of gene function from ancestral to modern day genes. One of the main applications of PANTHER is in accurate prediction of the functions of uncharacterized genes, based on their evolutionary relationships to genes with functions known from experiment. The PANTHER website, freely available at http://www.pantherdb.org, also includes software tools for analyzing genomic data relative to known and inferred gene functions. Since 2007, there have been several new developments to PANTHER: (i) improved phylogenetic trees, explicitly representing speciation and gene duplication events, (ii) identification of gene orthologs, including least diverged orthologs (best one-to-one pairs), (iii) coverage of more genomes (48 genomes, up to 87% of genes in each genome; see http://www.pantherdb.org/panther/summaryStats.jsp), (iv) improved support for alternative database identifiers for genes, proteins and microarray probes and (v) adoption of the SBGN standard for display of biological pathways. In addition, PANTHER trees are being annotated with gene function as part of the Gene Ontology Reference Genome project, resulting in an increasing number of curated functional annotations

Canalization of the evolutionary trajectory of the human influenza virus

Since its emergence in 1968, influenza A (H3N2) has evolved extensively in genotype and antigenic phenotype. Antigenic evolution occurs in the context of a two-dimensional 'antigenic map', while genetic evolution shows a characteristic ladder-like genealogical tree. Here, we use a large-scale individual-based model to show that evolution in a Euclidean antigenic space provides a remarkable correspondence between model behavior and the epidemiological, antigenic, genealogical and geographic patterns observed in influenza virus. We find that evolution away from existing human immunity results in rapid population turnover in the influenza virus and that this population turnover occurs primarily along a single antigenic axis. Thus, selective dynamics induce a canalized evolutionary trajectory, in which the evolutionary fate of the influenza population is surprisingly repeatable and hence, in theory, predictable.Comment: 29 pages, 5 figures, 10 supporting figure

Genomic Signature-Based Identification of Influenza A Viruses Using RT-PCR/Electro-Spray Ionization Mass Spectrometry (ESI-MS) Technology

BACKGROUND: The emergence and rapid spread of the 2009 H1N1 pandemic influenza A virus (H1N1pdm) in humans highlights the importance of enhancing the capability of existing influenza surveillance systems with tools for rapid identification of emerging and re-emerging viruses. One of the new approaches is the RT-PCR electrospray ionization mass spectrometry (RT-PCR/ESI-MS) technology, which is based on analysis of base composition (BC) of RT-PCR amplicons from influenza "core" genes. Combination of the BC signatures represents a "genomic print" of an influenza A virus. METHODOLOGY/PRINCIPAL FINDINGS: Here, 757 samples collected between 2006 and 2009 were tested, including 302 seasonal H1N1, 171 H3N2, 7 swine triple reassortants, and 277 H1N1pdm viruses. Of the 277 H1N1pdm samples, 209 were clinical specimens (throat, nasal and nasopharyngeal swabs, nasal washes, blood and sputum). BC signatures for the clinical specimen from one of the first cases of the 2009 pandemic, A/California/04/2009, confirmed it as an unusual, previously unrecognized influenza A virus, with "core" genes related to viruses of avian, human and swine origins. Subsequent analysis of additional 276 H1N1pdm samples revealed that they shared the genomic print of A/California/04/2009, which differed from those of North American swine triple reassortant viruses, seasonal H1N1 and H3N2 and other viruses tested. Moreover, this assay allowed distinction between "core" genes of co-circulating groups of seasonal H1N1, such as clades 2B, 2C, and their reassortants with dual antiviral resistance to adamantanes and oseltamivir. CONCLUSIONS/SIGNIFICANCE: The RT-PCR/ESI-MS assay is a broad range influenza identification tool that can be used directly on clinical specimens for rapid and accurate detection of influenza virus genes. The assay differentiates the H1N1pdm from seasonal and other nonhuman hosts viruses. Although not a diagnostic tool, this assay demonstrates its usefulness and robustness in influenza virus surveillance and detection of novel and unusual viruses with previously unseen genomic prints

Discovering the Phylodynamics of RNA Viruses

The advent of extremely high throughput DNA sequencing ensures that genomic data from microbial organisms can be acquired in unprecedented quantities and with remarkable rapidity. Although this genomic revolution will affect all microbes alike, our focus here is on RNA viruses, as the rapidity of their evolution, which is observable over the time scale of human observation, allows phylodynamic inferences to be made with great precision. In the foreseeable future it is likely that complete genome sequencing will become the standard method of viral characterization, providing the highest possible resolution for phylogenetic studies. The rapidity with which genome sequence data were generated from the ongoing epidemic of swine-origin H1N1 influenza A virus [1] is testament to the power of this technology

Confronting chemobrain: an in-depth look at survivors’ reports of impact on work, social networks, and health care response

Mild cognitive impairment following chemotherapy is one of the most commonly reported post treatment symptoms by breast cancer survivors. This deterioration in cognitive function, commonly referred to as “chemobrain” or “chemofog,” was largely unacknowledged by the medical community until recent years. Although chemobrain has now become the subject of more vigorous exploration, little is known about this specific phenomenon’s psychosocial impact on breast cancer survivors. This research documents in-depth the effects that cognitive impairment has on women’s personal and professional lives, and our data suggest that greater attention needs to be focused on this arena of survivorship. The results are based on an in-depth qualitative study of 74 white and African American breast cancer survivors in California who experience post-treatment side effects. The data reported herein were obtained through the use of focus groups and in-depth interviews. Our data indicate that cognitive impairment can be problematic for survivors, with many asserting that it is their most troublesome post treatment symptom. Survivors report diminished quality of life and daily functioning as a result of chemobrain. Respondents detail a range of coping strategies that they are forced to employ in order to manage their social and professional lives. Chemobrain significantly impairs a proportion of cancer survivors, at great cost to them economically, emotionally, and interpersonally. This suggests that more research needs to be conducted on the psychosocial ramifications of post treatment symptoms in order to inform the efforts of the medical and mental health communities as well as the support networks of survivors. A better and broader understanding of the effects of cognitive impairment both in the medical community and among lay people could pave the way for improved social and psychological services for this population

OrthoDB: the hierarchical catalog of eukaryotic orthologs in 2011

The concept of homology drives speculation on a gene’s function in any given species when its biological roles in other species are characterized. With reference to a specific species radiation homologous relations define orthologs, i.e. descendants from a single gene of the ancestor. The large-scale delineation of gene genealogies is a challenging task, and the numerous approaches to the problem reflect the importance of the concept of orthology as a cornerstone for comparative studies. Here, we present the updated OrthoDB catalog of eukaryotic orthologs delineated at each radiation of the species phylogeny in an explicitly hierarchical manner of over 100 species of vertebrates, arthropods and fungi (including the metazoa level). New database features include functional annotations, and quantification of evolutionary divergence and relations among orthologous groups. The interface features extended phyletic profile querying and enhanced text-based searches. The ever-increasing sampling of sequenced eukaryotic genomes brings a clearer account of the majority of gene genealogies that will facilitate informed hypotheses of gene function in newly sequenced genomes. Furthermore, uniform analysis across lineages as different as vertebrates, arthropods and fungi with divergence levels varying from several to hundreds of millions of years will provide essential data for uncovering and quantifying long-term trends of gene evolution. OrthoDB is freely accessible from http://cegg.unige.ch/orthodb

The supportive care needs of women experiencing gynaecological cancer: a Western Australian cross-sectional study

Background: Women diagnosed with gynaecological cancer experience supportive care needs that require care provision to reduce the impact on their lives. International evidence suggests supportive care needs of women with gynaecological cancer are not being met and provision of holistic care is a priority area for action. Knowledge on gynaecological cancer supportive care needs is limited, specifically comparison of needs and cancer gynaecological subtype. Our aim was to identify supportive care needs of Western Australian women experiencing gynaecological cancer, their satisfaction with help and explore associations between participant’s demographic characteristics and identified needs. Methods: A cross-sectional design incorporating a modified version of the Supportive Care Needs Survey - short form (SCNS-SF34) assessed 37 supportive care needs under five domains in conjunction with demographic data. Three hundred and forty three women with gynaecological cancer attending a tertiary public referral hospital completed the survey over 12 months. Statistical analysis was performed using the R environment for statistical computing. A linear regression model was fitted with factor scores for each domain and demographic characteristics as explanatory variables. Results: Three hundred and three women (83%) identified at least one moderate or high level supportive care need. The five highest ranked needs were, ‘being informed about your test results as soon as feasible’ (54.8%), ‘fears about cancer spreading’ (53.7%), ‘being treated like a person not just another case’ (51.9%), ‘being informed about cancer which is under control or diminishing (that is, remission)’ (50.7%), and ‘being adequately informed about the benefits and side-effects of treatments before you choose to have them’ (49.9%). Eight of the top ten needs were from the ‘health system and information’ domain. Associations between supportive care items and demographic variables revealed ‘cancer type’, and ‘time since completion of treatment’ had no impact on level of perceived need for any domain. Conclusions: Western Australian women with gynaecological cancer identified a high level of supportive care needs. The implementation of a supportive care screening tool is recommended to ensure needs are identified and care is patient-centred. Early identification and management of needs may help to reduce the burden on health system resources for managing ongoing needs