Using near-term forecasts and uncertainty partitioning to inform prediction of oligotrophic lake cyanobacterial density.

Near-term ecological forecasts provide resource managers advance notice of changes in ecosystem services, such as fisheries stocks, timber yields, or water quality. Importantly, ecological forecasts can identify where there is uncertainty in the forecasting system, which is necessary to improve forecast skill and guide interpretation of forecast results. Uncertainty partitioning identifies the relative contributions to total forecast variance introduced by different sources, including specification of the model structure, errors in driver data, and estimation of current states (initial conditions). Uncertainty partitioning could be particularly useful in improving forecasts of highly variable cyanobacterial densities, which are difficult to predict and present a persistent challenge for lake managers. As cyanobacteria can produce toxic and unsightly surface scums, advance warning when cyanobacterial densities are increasing could help managers mitigate water quality issues. Here, we fit 13 Bayesian state-space models to evaluate different hypotheses about cyanobacterial densities in a low nutrient lake that experiences sporadic surface scums of the toxin-producing cyanobacterium, Gloeotrichia echinulata. We used data from several summers of weekly cyanobacteria samples to identify dominant sources of uncertainty for near-term (1- to 4-week) forecasts of G. echinulata densities. Water temperature was an important predictor of cyanobacterial densities during model fitting and at the 4-week forecast horizon. However, no physical covariates improved model performance over a simple model including the previous week's densities in 1-week-ahead forecasts. Even the best fit models exhibited large variance in forecasted cyanobacterial densities and did not capture rare peak occurrences, indicating that significant explanatory variables when fitting models to historical data are not always effective for forecasting. Uncertainty partitioning revealed that model process specification and initial conditions dominated forecast uncertainty. These findings indicate that long-term studies of different cyanobacterial life stages and movement in the water column as well as measurements of drivers relevant to different life stages could improve model process representation of cyanobacteria abundance. In addition, improved observation protocols could better define initial conditions and reduce spatial misalignment of environmental data and cyanobacteria observations. Our results emphasize the importance of ecological forecasting principles and uncertainty partitioning to refine and understand predictive capacity across ecosystems.

The DNA sequence and biological annotation of human chromosome 1.

The reference sequence for each human chromosome provides the framework for understanding genome function, variation and evolution. Here we report the finished sequence and biological annotation of human chromosome 1. Chromosome 1 is gene-dense, with 3,141 genes and 991 pseudogenes, and many coding sequences overlap. Rearrangements and mutations of chromosome 1 are prevalent in cancer and many other diseases. Patterns of sequence variation reveal signals of recent selection in specific genes that may contribute to human fitness, and also in regions where no function is evident. Fine-scale recombination occurs in hotspots of varying intensity along the sequence, and is enriched near genes. These and other studies of human biology and disease encoded within chromosome 1 are made possible with the highly accurate annotated sequence, as part of the completed set of chromosome sequences that comprise the reference human genome.

The DNA sequence and analysis of human chromosome 6.

Chromosome 6 is a metacentric chromosome that constitutes about 6% of the human genome. The finished sequence comprises 166,880,988 base pairs, representing the largest chromosome sequenced so far. The entire sequence has been subjected to high-quality manual annotation, resulting in the evidence-supported identification of 1,557 genes and 633 pseudogenes. Here we report that at least 96% of the protein-coding genes have been identified, as assessed by multi-species comparative sequence analysis, and provide evidence for the presence of further, otherwise unsupported exons/genes. Among these are genes directly implicated in cancer, schizophrenia, autoimmunity and many other diseases. Chromosome 6 harbours the largest transfer RNA gene cluster in the genome; we show that this cluster co-localizes with a region of high transcriptional activity. Within the essential immune loci of the major histocompatibility complex, we find HLA-B to be the most polymorphic gene on chromosome 6 and in the human genome.

Characterization of clustered MHC-linked olfactory receptor genes in human and mouse.

Olfactory receptor (OR) loci frequently cluster and are present on most human chromosomes. They are members of the seven transmembrane receptor (7-TM) superfamily and, as such, are part of one of the largest mammalian multigene families, with an estimated copy number of up to 1000 ORs per haploid genome. As their name implies, ORs are known to be involved in the perception of odors and possibly also in other, nonolfaction-related, functions. Here, we report the characterization of ORs that are part of the MHC-linked OR clusters in human and mouse (partial sequence only). These clusters are of particular interest because of their possible involvement in olfaction-driven mate selection. In total, we describe 50 novel OR loci (36 human, 14 murine), making the human MHC-linked cluster the largest sequenced OR cluster in any organism so far. Comparative and phylogenetic analyses confirm the cluster to be MHC-linked but divergent in both species and allow the identification of at least one ortholog that will be useful for future regulatory and functional studies. Quantitative feature analysis shows clear evidence of duplications of blocks of OR genes and reveals the entire cluster to have a genomic environment that is very different from its neighboring regions. Based on in silico transcript analysis, we also present evidence of extensive long-distance splicing in the 5'-untranslated regions and, for the first time, of alternative splicing within the single coding exon of ORs. Taken together with our previous finding that ORs are also polymorphic, the presented data indicate that the expression, function, and evolution of these interesting genes might be more complex than previously thought.

A physical map of the human genome.

The human genome is by far the largest genome to be sequenced, and its size and complexity present many challenges for sequence assembly. The International Human Genome Sequencing Consortium constructed a map of the whole genome to enable the selection of clones for sequencing and for the accurate assembly of the genome sequence. Here we report the construction of the whole-genome bacterial artificial chromosome (BAC) map and its integration with previous landmark maps and information from mapping efforts focused on specific chromosomal regions. We also describe the integration of sequence data with the map.

The physical maps for sequencing human chromosomes 1, 6, 9, 10, 13, 20 and X.

We constructed maps for eight chromosomes (1, 6, 9, 10, 13, 20, X and (previously) 22), representing one-third of the genome, by building landmark maps, isolating bacterial clones and assembling contigs. By this approach, we could establish the long-range organization of the maps early in the project, and all contig extension, gap closure and problem-solving was simplified by containment within local regions. The maps currently represent more than 94% of the euchromatic (gene-containing) regions of these chromosomes in 176 contigs, and contain 96% of the chromosome-specific markers in the human gene map. By measuring the remaining gaps, we can assess chromosome length and coverage in sequenced clones.

An integrated map of human 6q22.3-q24 including a 3-Mb high-resolution BAC/PAC contig encompassing a QTL for fetal hemoglobin.

Genetic studies have previously assigned a quantitative trait locus (QTL) for hemoglobin F and F cells to a region of approximately 4 Mb between the markers D6S408 and D6S292 on chromosome 6q23. An initial yeast artificial chromosome contig of 13 clones spanning this region was generated. Further linkage analysis of an extended kindred refined the candidate interval to 1-2 cM, and key recombination events now place the QTL within a region of <800 kb. We describe a high-resolution bacterial clone contig spanning 3 Mb covering this critical region. The map consists of 223 bacterial artificial chromosome (BAC) and 100 P1 artificial chromosome (PAC) clones ordered by sequence-tagged site (STS) content and restriction fragment fingerprinting with a minimum tiling path of 22 BACs and 1 PAC. A total of 194 STSs map to this interval of 3 Mb, giving an average marker resolution of approximately one per 15 kb. About half of the markers were novel and were isolated in the present study, including three CA repeats and 13 single nucleotide polymorphisms. Altogether 24 expressed sequence tags, 6 of which are unique genes, have been mapped to the contig.

Rapid delipidation of and particulate removal from human serum by membrane filtration in a tangential flow system.

Approximately 50% of the total lipids and virtually all of the colloids and particulates which impart turbidity to human serum are removed by filtration through 0.1 micrometer-poresize membrane filters in a high-volume tangential flow device. The advantages of the method over solvent extraction are: (a) no organic solvent(s) is added to the serum at any time, (b) filtrations can be performed rapidly at room temperature, (c) unstable lipoproteins and particulates are removed in 1 step, (d) scaleup from hundreds of ml to hundreds of liters is readily achievable, and(e) process time is markedly reduced.