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A00-201 exam Format | A00-201 Course Contents | A00-201 Course Outline | A00-201 exam Syllabus | A00-201 exam Objectives


SAS Certified Specialist: Base Programming Using SAS 9.4
Read and create data files.
Manipulate and transform data.
Create basic detail and summary reports using Base SAS procedures.
Identify and correct syntax and programming logic errors.

Access and Create Data Structures
Create Temporary and permanent SAS Data sets.
Investigate SAS data libraries using base SAS utility procedures.
Access data.
Combine SAS data sets.
Create and manipulate SAS date values.
Control which observations and variables in a SAS data set are processed and output.
Manage Data
Sort observations in a SAS data set.
Conditionally execute SAS statements.
Use assignment statements in the DATA step.
Modify variable attributes using options and statements in the DATA step.
Accumulate sub-totals and totals using DATA step statements.
Use SAS functions to manipulate character data, numeric data, and SAS date values.
Use SAS functions to convert character data to numeric and vice versa.
Process data using DO LOOPS.
Restructure SAS data sets with PROC TRANSPOSE.
Use macro variables to simplify program maintenance.
Error Handling
Identify and resolve programming logic errors.
Recognize and correct syntax errors.
Generate Reports and Output
Generate list reports using the PRINT procedure.
Generate summary reports and frequency tables using base SAS procedures.
Enhance reports with user-defined formats, titles, footnotes and SAS System reporting options.
Generate reports using ODS statements.
Export data.



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SNPing Away at Genome-extensive sickness association reviews | A00-201 Braindumps and PDF Download

August eight, 2007 | This year has viewed a torrent of stories in scientific journals and mainstream media announcing the results of stories linking a gene variant to an extended chance for regular diseases — diabetes, Alzheimer’s disorder, and heart disorder, as an instance. as the ny instances mentioned lately, “The surprising spate of accurate genes marks an acceleration, and maybe a turning aspect, within the means to find sickness genes.”

fresh breakthroughs consist of the discovery of dissimilar genetic versions linked to class 2 diabetes, because of genome-huge association (GWA) efforts by means of consortia led with the aid of the vast Institute’s David Altshuler (Science 316,1331-1336; 2007), Michigan’s Michael Boehnke (Science 316,1341-1345; 2007), and Oxford college’s Mark McCarthy ( Science, 316,1336-1341; 2007), as well as by deCODE Genetics. The Icelandic company became additionally the source of a July report in Nature (doi:10.1038/nature06007) linking two editions to possibility of atrial fibrillation, essentially the most standard heart arrhythmia. curiously, the mutations lie adjacent to a gene typical to be panic in coronary heart building. And in June, deCODE reported that a typical variant on chromosome 9 impacts the possibility of myocardial infarction (Science 316,1491-1493; 2007).

Alzheimer’s disorder has been yet another focal aspect for GWA studies. A joint effort by using the Phoenix-primarily based Translational Genomics analysis Institute and other Arizona Alzheimer’s agencies surveyed greater than 500,000 SNPs and recognized six editions in the GRB-linked binding protein 2 (GAB2) gene associated with late-onset Alzheimer’s disease (Neuron fifty four, 713-720; 2007). an additional business-academia collaboration with PGxHealth (New Haven, CT) researching schizophrenia used 500,000 markers to pinpoint several novel infrequent mutations in a cytokine receptor gene (Molec Psych 12, 572-580; 2007). The community concluded that this candidate gene might aid explain epidemiologic facts suggesting an accelerated risk for schizophrenia in individuals with autoimmune problems, prenatal infection, and familial leukemia.

In can also, stories in Nature (447,1087-1093; 2007) and Nature Genetics (39, 870-874; 2007 and 39, 865-869; 2007) recognized up to 5 general genetic editions that confer an accelerated chance of breast cancer. These findings emanated from a consortium led by means of Doug Easton (cancer analysis UK), David starvation (Harvard school of Public fitness), and deCODE.

Mapping sickness-linked genes and SNPs marks the beginning of a brand new genomic revolution so one can see the convergence of sequencing statistics, genotyping information, differential gene expression statistics, pedigree and population data, old/archived records, and clinical statistics to allow the evaluation of disorder chance, e book screening efforts, and pave the way for disorder prevention options, early prognosis, safer and more advantageous remedies, and more suitable prognostic equipment.

a number of elements are riding the dramatic discovery of those gene-sickness associations, above all exponential improvements in hardware and application that permit significant-scale GWA experiences. And contributing to the ease of implementation of this evolving know-how base is the cooperative effort among the many supplier group to maximize compatibility of the hardware and utility.

Hardware and application suppliers rightfully claim a contributory position in accelerating the lengthy-awaited effects of significant-scale GWA reviews. although it is the synergism between microarray platforms, utility, and user knowledge and comments that represents the best spark igniting the existing firestorm of SNP/sickness associations, companies want to tout their contributions. as an instance, Affymetrix would like you to know that its know-how changed into used with the aid of the Wellcome have confidence Case manage Consortium for a huge look at of 14,000 circumstances of seven general diseases (Nature 447, 661-678, 2007; see p. 6). And Illumina technology became at the coronary heart of contemporary GWA reports of prostate melanoma and amyotrophic lateral sclerosis.

The Affymetrix Genome-huge Human SNP Array 6.0 GeneChip, brought in may additionally, contains essentially one million probes for detecting single nucleotide polymorphisms (SNPs) and duplicate number versions (CNV) (See “adding CNVs to the combine”). In June, Illumina launched a more than 1-million SNP chip — the Human1M DNA analysis BeadChip — that additionally comprises about 50,000 probes focused to genomic hotspots for CNVs.

These two microarray rivals are sarcastically furthering collaboration throughout trade and academia by using advancing big-scale genotyping efforts. Affymetrix has a GeneChip Consortia software and the Affymetrix builders’ network, a forum for application developers. The Illumina-join bioinformatics software partnership, launched in may, comprises organizations comparable to Biocomputing structures, GenoLogics, GeneData, GeneSifter, Golden Helix, InforSense, Ingenuity systems, Partek Genomics, Rosetta BioSoftware, Sapio Sciences, and SAS/JMP Genomics. accomplice businesses create custom-made plug-ins that facilitate integration of their algorithms and information applications with the records generated on Illumina or Affymetrix systems and application.

“Our partners obviously ... recognize that no single software answer will meet the wants of all researchers,” says Omoshile Clement, Illumina’s senior product supervisor of structures. “The purpose is to shorten the time and Strengthen the best of facts analysis, make sure that the informatics component of GWA is not a bottleneck, and enable a seamless transfer of records from the microarray platform to distinct computational functions.” In June, Illumina initiated iControlDB, a genotyping handle repository for use via researchers conducting case-handle GWA reviews. The purpose is to deliver access to a set of genotypes from practically 10,000 control samples.

A Turning PointA host of new computational strategies and equipment are expanding the speed and breadth of information analysis and the statistical power of GWA reviews. they're also driving improvements within the QA/QC of genotyping tasks and provoking fresh self belief in the magnitude of disorder association experiences. this is a must have as researchers move past the low placing fruit, or greater intuitive disorder-gene linkages, and start discovering diversifications in genes that don't seem to be necessarily energetic in pathways or related to customary sickness processes.

“it's important to build into the utility avoidance of flaws and statistical error, so users aren't producing spurious association consequences,” says Andy Ferrin, VP of earnings and advertising at Golden Helix. as with any experimental approach, GWA comes with noise and limitations. All too often, researchers do not avail themselves of the capabilities of statisticians when designing an test, says Brian Gilman, president of Panther Informatics and SciLink. The main statistical challenge in GWA reports considerations the “capabilities for inherent flaws, exceptionally when combining experimental systems,” says Gilman. An example could be analyzing case-control facts from an Affymetrix or Illumina platform with a greater focused SNP evaluation the usage of the Sequenom platform.

“The biggest use of utility techniques in large-scale genotyping initiatives these days is for performing QC and QA” — laboratory suggestions administration types of applications, says Gilman. corporations should evaluate the raw statistics and determine the nice of the pattern recognizing, the effective and negative controls, the best of the chips, and the records output.

Gilman says the enhancing working relationship between business and academic partners represents a huge alternate, enabling businesses to recognize early on the boundaries of their application platforms, allowing rapid improvements to industrial products. “I believe americans now more desirable understand the use and boundaries of a platform for a particular variety of study,” says Gilman, thereby contributing to the glut of accurate GWA wins.

monitoring a ailment-linked SNP is one issue, but researchers want “to take into account the biological context and importance of the statistical association,” says Megan Laurance, senior scientist at Ingenuity systems. certainly, many certified see a shift from essential genetic confirmation — copy of an affiliation in a 2nd population — to systematic functional confirmation stories, which validate the effects by using thinking of the organic context of the variation in selected genes.

Ingenuity’s flagship product, Ingenuity Pathways evaluation, takes experimentally derived gene lists and plugs them into the utility to establish which pathways, mobile methods, disease phenotypes, and molecular interactions are implicated for a particular set of genes.

“The problem on the application facet is to provide a fluid workflow,” says Laurance. as an example, the UC-Santa Cruz “Golden course” Genome Browser is a favored portal for choosing SNPs and mapping genes. Ingenuity ensures that its software helps analysis workflows from the browser, allowing clients to extract and plug genes into Ingenuity software and put them right into a organic context. Laurance provides that, “for pharma companies that usually have huge bioinformatics/computational teams and might be ahead of public mapping efforts, they supply programmatic tools that facilitate a seamless link to their purposes.”

Commenting on the value of compatibility with the leading microarray structures, Kevin Cramer, CEO of utility producer Sapio Sciences, builders of Exemplar LIMS and Exemplar Analytics for genotyping statistics, says, “Ninety p.c of the challenge is not in working the application however quite within the upfront loading and formatting of the facts.” records input must be as seamless as viable and accommodate researchers the use of various public domain and seller tools, each and every with their own odd or proprietary information codecs.

Illumina’s Clement identifies a couple of key challenges, including the need for stronger statistical vigor to mine massive datasets and achieve P values that yield at least an 80% self assurance interval. Ideally, novel computational and information analysis methods could boost statistical power with out the need to move to better demo sizes, by way of maximizing the signal-to-noise ratio of GWA reviews. “The crown jewel will be the means to resequence a specific SNP/gene and validate it as a biologically crucial marker for a selected ailment,” says Clement.

traits and TrajectoriesThe incorporation of increasingly different sorts of data in GWA reviews, akin to analyses of methylation patterns, is pressuring software establishments to increase loads of solutions. an additional precedence within the evolution of GWA utility is to make it more purchasable to a broader range of end-users, together with clinicians who could be making use of the results to patient populations to book screening, diagnostic, prognostic, and treatment planning selections.

“With the rate of genotyping plummeting, the density of chips expanding,” and the variety of GWA studies international hovering, “it is no longer useful for the entire records analysis to be executed by using statistical geneticists at massive institutions,” says Ferrin of Golden Helix. The secret is to strike a stability between featuring potent functionality in an intuitive yet bendy workflow that can be simply applied through non-programmers and non-statisticians.

As businesses are more and more fitting overloaded with raw microarray data, application providers are moving toward novel records administration options. These will even have a vital position in assisting conclusion-users leverage ancient datasets to operate enormous comparative, population-based mostly reviews. “there's a robust should take legacy information and merge it with the records being generated nowadays,” says Sasha Paegle, senior product manager at Rosetta BioSoftware.

Recognizing the “intimate relationship” between statistical geneticists, clinicians, and genotyping core organizations, Rosetta designed its Syllego equipment to provide a assignment workspace for organizing genotype and reference facts, to provide context to the analysis effects and provide a method to share the outcomes. Says Paegle: “The aim is to permit scientists to resolve their scientific query the use of computational strategies or tools of their deciding on.”

“Genetics is an ‘ancient’ container,” says Paegle, “and as a consequence there are many different file formats, which introduces some friction between collaborators,” who want to share both uncooked data and evaluation outcomes. “there's at present no constant approach to share records,” Paegle provides.

Partek’s GS utility “combines potent statistical analysis, interactive visualization, is clever concerning the human genome, and has a person interface designed to be used via the scientist — inserting the evaluation into the fingers of the clinical researcher,” says Partek president and CEO, Tom Downey.

transferring the BottleneckThe growing to be variety of GWA facts points is marvelous, with 1-million SNP microarrays and GWA studies comprising up to 20,000 patient samples. Some agencies are even thinking of reports as much as one hundred,000 sufferers, says Christophe Lambert, president and CEO of Golden Helix. The boom in genotyping chip density is even exceeding Moore’s legislation, up some tenfold during the past 18 months, estimates Lambert. “if you happen to believe the two gigabyte limit of 32-bit structure processors, we’re starting to hit a wall,” he says.

These increasing numbers have compelled groups to conform. four years ago, Sapio Sciences took root within the days when state-of-the-paintings expertise changed into the Affymetrix 10K Array, recalls CEO Cramer. over the years the business has brought clustering, haplotype analysis, quantitative trait evaluation, gene ontology mapping, and, most lately, covariate analysis modules to its Exemplar evaluation Suite. Cramer says Sapio’s most accurate product release can wholly make the most of three GB of reminiscence (employing a 3-GB change within the boot file of home windows XP knowledgeable or Server) permitting clients to manner 50% more samples than with a standard 2-GB device.

but the regular view that hardware, certainly memory potential, limits the evaluation of big datasets is “a huge fallacy in the industry,” says Gilman of SciLink. Bioinformaticians are typically no longer desktop scientists, nor are they trained in how to use memory efficiently and the way to tweak a equipment or algorithm to maximise computer efficiency.

BC/SNPmax is Finland’s Biocomputing structures’ scaleable database administration system for GWA that facilitates the assortment and integration of genotype and phenotype information and the interface with downstream records evaluation equipment. “We focal point on the workflows in a examine and [by creating a user-defined interface] make it possible to cut up an issue into small items, run these in parallel in a computer cluster, and link to distinctive analytical tools,” says Timo Kanninen, Biocomputing’s founder and know-how director.

The genome work pioneered in big genome facilities is spreading to smaller corporations that customarily lack the tools or potential to create their own utility environments for managing facts. From a funding standpoint, Pekka Mäkelä, managing director of Biocomputing structures, observes that whereas furnish cash has been with no trouble purchasable to strengthen GWA hardware, funding companies “now are looking to see a neatly-developed plan to manage and analyze the statistics” and are more inclined to deliver dollars to aid bioinformatics needs.

One might debate the relative deserves of distributed or grid computing ideas for sharing the burden of totally records-intensive analyses across varied processors observed both within a computer or throughout tens, hundreds, or thousands of CPUs. despite the accurate strategy, grid computing offers a possible solution to the want for increased pace and reminiscence skill for GWA experiences. assorted computers can independently analyze small packets of records, such as discrete ranges of SNPs, and the accumulated records can then be combined, interpreted, and introduced to the consumer.

Golden Helix has developed a GWA grid answer that may control the statistics produced through the next technology of GWA structures using chips with greater than 1000000 SNPs and tens of hundreds of affected person samples. compared to the open supply concepts frequently developed in academia to deal with GWA statistics in batch jobs, Lambert says that this product can “interactively video display the progress of these batch jobs in the context of their consumer interface.” That interface helps each the Condor Pool (a grid equipment developed at the institution of Wisconsin) and United gadget’s Grid MP frameworks.

For now, even though, in keeping with Josh Forsythe, advertising and marketing director at Golden Helix, the enterprise’s HelixTree application can operate interactive GWA studies on a typical computing device in a reasonable time. for example, HelixTree utility changed into deployed in a contemporary study that identified a schizophrenia susceptibility locus carried out in a number of hundred patients the usage of the Affymetrix 500K Array (Molec Psychiatry 12, 572-580; 2007). Forsythe provides that HelixTree has been successfully used internally at the side of the Affymetrix SNP GeneChip 6.0 Array.

In the same vein, Agilent’s computing device device, GeneSpring GT, has been used to analyze high volume, high density genotyping facts in combination with GeneSpring GX for gene expression facts analysis to look at schizophrenia and bipolar sickness.

Prepping for personalised MedicineIn may also, SAS Institute hosted the FDA-led MicroArray exceptional handle Consortium (MAQC), which is conducting a analyze of microarray know-how. MAQC contributors from SAS have been the use of the company’s JMP Genomics application to investigate the MAQC datasets and reveal consequences in a graphical structure. The consortium recently shaped a subgroup so one can focal point on GWA studies, proof of the growing interest in the usage of microarray information to foretell disease risk and medical results as part of the vogue towards personalised medication.

JMP Genomics is a device for importing, inspecting, and visualizing SNP, expression, and proteomics data. Designed for users with limited programming abilities, it permits them to entry advanced SAS genetic analysis equipment. Russ Wolfinger, SAS’ director of scientific discovery and genomics, says the business’s application can also be used to visualize genotyping data, plotting P values alongside a representation of a chromosome, with peaks revealing hotspots of affiliation. “From this excessive stage field of regard of the statistics, the application permits you to spotlight essentially the most massive consequences and ‘drill down’” to center of attention on these gene regions, says Wolfinger.

JMP Genomics can perform predominant add-ons evaluation of genetics facts to look for population substructures or family relationships. primary add-ons evaluation is certainly one of a couple of dimension discount techniques that may also be used to establish patterns or developments in records.

InforSense’s analytical workflow platform ambitions translational analysis initiatives and is designed to help scientific hypothesis era. “Researchers use the business’s ClinicalSense product, which makes it possible for you to slice and cube through large datasets, to generate affected person subpopulations similar to responders versus non-responders,” explains CSO Jonathan Sheldon.

Describing that as a “logical entry element into a personalized medicine analyze,” Sheldon says that combining ClinicalSense with the more accurate GenSense genome-extensive genetic analysis application package helps determine the genetic foundation for these alterations.

“the way you interpret the statistical effects and share them with the wider person neighborhood is a challenge for the GWA field,” says Sheldon, describing the interactive portal approach InforSense took in designing GenSense, which “permits non-statisticians to make organic sense of genetic stories conducted on the whole genome scale.”

Panther’s Gilman predicts that the subsequent evolution of GWA know-how should be to use the haplotype map as a tool for stratifying affected person populations for clinical trial and pharmacogenomic applications.

In Spring 2007, Washington school’s Genome Sequencing middle (GSC) obtained a $156 million, 4-12 months furnish from the country wide Human Genome analysis Institute (NHGRI). “we are moving further and further to a medicinal focal point, re-sequencing regions of the human genome and concentrated on genes of hobby for distinctive diseases,” says GSC assistant director David Dooling. “we're using expression array and information on [CNVs] and loss of heterozygosity to inform selections on which regions [of the genome] to re-sequence.”

For now, complete genome SNP and CNV analysis are assisting to map regions of pastime for clinical sequencing, however Dooling predicts, “complete-genome sequence is not too a long way off, making genome-extensive analysis on the sequence stage viable.”

Genizon BioScience’s John Raelson is of the same opinion that entire-genome sequencing expertise will probably dominate the genome analysis landscape inside the next 5 years. “The true future [for GWA studies] may be in pharmacogenomics, incorporating an entire genome affiliation study into a medical trial to determine genes affecting response to a drug,” says Raelson.

Sidebar: Genizon Horizon

The Montreal company Genizon BioSciences leverages its entry to DNA samples from more than 50,000 subjects within the Quebec French Canadian founder inhabitants to look at the genetic groundwork of 25 diseases (See “The Galileo Code,” Bio•IT World, Feb. 2005). The business has achieved ten entire genome scans, together with Crohn’s sickness, bronchial asthma, Alzheimer’s disease, schizophrenia, and a spotlight deficit hyperactivity sickness.

Genizon’s IT infrastructure comprises an FDA-compliant LabVantage Sapphire LIMS, an eResearch technology medical Database management system with digital statistics seize and signature capabilities, a 32-terabyte storage area network, and a 288-CPU computing grid for facts analysis.

Borivoj (Bora) Stojkovic, Genizon’s application architecture chief, describes the business’s proactive approach to the inexorable increase in SNP densities and GWA pattern sizes. Genizon simulates giant datasets to determine and Strengthen methods aimed at preempting current bottlenecks. by way of experimenting with compressed models of the datasets, “we will load them into reminiscence and nonetheless have access to the entire facts with out chewing up all of their memory,” says Stojkovic. “We need to decompose the area with a view to converge to a smaller dataset,” partitioning the statistics into smaller blocks and then processing particular person blocks the usage of assorted CPUs.

Stojkovic says Genizon’s latest compression thoughts will reduce the company’s file storage footprint “with the aid of a factor of up to 20.” At a considerable number of compute-intensive levels of an analysis, Genizon may partition its databases amongst grids and clusters built-in into its pipeline. The business’s interior grid automatically distributes the statistics among hundreds of CPUs in a cluster. To manage various kinds of records, Genizon standardizes by itself inner information layout, funneling records from external sources through conversion filters.

Stojkovic emphasizes, although, that whereas relying on a lot of strategies to allotted or grid computing presents definite benefits, the first purpose should still be to streamline and optimize the computational thought techniques and the algorithmic fluency, improving integration and hyperlinks, and to tighten and refine the language and circulation.

Subscribe to Bio-IT World magazine.


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