A single-array preprocessing method for estimating full-resolution raw copy numbers from all Affymetrix genotyping arrays including GenomeWideSNP 5 & 6

Motivation: High-resolution copy-number (CN) analysis has in recent years gained much attention, not only for the purpose of identifying CN aberrations associated with a certain phenotype, but also for identifying CN polymorphisms. In order for such studies to be successful and cost effective, the statistical methods have to be optimized. We propose a single-array preprocessing method for estimating full-resolution total CNs. It is applicable to all Affymetrix genotyping arrays, including the recent ones that also contain non-polymorphic probes. A reference signal is only needed at the last step when calculating relative CNs. Results: As with our method for earlier generations of arrays, this one controls for allelic crosstalk, probe affinities and PCR fragment-length effects. Additionally, it also corrects for probe sequence effects and co-hybridization of fragments digested by multiple enzymes that takes place on the latest chips. We compare our method with Affymetrix's CN5 method and the dChip method by assessing how well they differentiate between various CN states at the full resolution and various amounts of smoothing. Although CRMA v2 is a single-array method, we observe that it performs as well as or better than alternative methods that use data from all arrays for their preprocessing. This shows that it is possible to do online analysis in large-scale projects where additional arrays are introduced over time. Availability: A bounded-memory implementation that can process any number of arrays is available in the open source R package aroma.affymetrix. Contact: [email protected] Supplementary information: Supplementary data are available at Bioinformatics onlin

The influence of feature selection methods on accuracy, stability and interpretability of molecular signatures

Motivation: Biomarker discovery from high-dimensional data is a crucial problem with enormous applications in biology and medicine. It is also extremely challenging from a statistical viewpoint, but surprisingly few studies have investigated the relative strengths and weaknesses of the plethora of existing feature selection methods. Methods: We compare 32 feature selection methods on 4 public gene expression datasets for breast cancer prognosis, in terms of predictive performance, stability and functional interpretability of the signatures they produce. Results: We observe that the feature selection method has a significant influence on the accuracy, stability and interpretability of signatures. Simple filter methods generally outperform more complex embedded or wrapper methods, and ensemble feature selection has generally no positive effect. Overall a simple Student's t-test seems to provide the best results. Availability: Code and data are publicly available at http://cbio.ensmp.fr/~ahaury/

Test of Four Colon Cancer Risk-Scores in Formalin Fixed Paraffin Embedded Microarray Gene Expression Data

Background Prognosis prediction for resected primary colon cancer is based on the T-stage Node Metastasis (TNM) staging system. We investigated if four well-documented gene expression risk scores can improve patient stratification. Methods Microarray-based versions of risk-scores were applied to a large independent cohort of 688 stage II/III tumors from the PETACC-3 trial. Prognostic value for relapse-free survival (RFS), survival after relapse (SAR), and overall survival (OS) was assessed by regression analysis. To assess improvement over a reference, prognostic model was assessed with the area under curve (AUC) of receiver operating characteristic (ROC) curves. All statistical tests were two-sided, except the AUC increase. Results All four risk scores (RSs) showed a statistically significant association (single-test, P < .0167) with OS or RFS in univariate models, but with HRs below 1.38 per interquartile range. Three scores were predictors of shorter RFS, one of shorter SAR. Each RS could only marginally improve an RFS or OS model with the known factors T-stage, N-stage, and microsatellite instability (MSI) status (AUC gains < 0.025 units). The pairwise interscore discordance was never high (maximal Spearman correlation = 0.563) A combined score showed a trend to higher prognostic value and higher AUC increase for OS (HR = 1.74, 95% confidence interval [CI] = 1.44 to 2.10, P < .001, AUC from 0.6918 to 0.7321) and RFS (HR = 1.56, 95% CI = 1.33 to 1.84, P < .001, AUC from 0.6723 to 0.6945) than any single score. Conclusions The four tested gene expression-based risk scores provide prognostic information but contribute only marginally to improving models based on established risk factors. A combination of the risk scores might provide more robust information. Predictors of RFS and SAR might need to be differen

FAKTOR INTERNAL DAN FAKTOR EKSTERNAL DALAM PENGEMBANGAN WISATA OLAHRAGA DI JAKABARING SPORTY CITY

Bagaimana strategi Dinas Pariwisata Kota Palembang dalam upaya pengembangan wisata olahraga di Jakabaring Sport City menggunakan metode alat analisis SWOT tujuan penelitian ini yaitu untuk mengetahui strategi pengembangan wisata olahraga di Jakabaring Sport City metode yang digunakan peneliti pada penelitian ini adalah metode penelitian langsung ke tempat penelitian (field research), dan pendekatan dengan SWOT secara kuantitatif. Analisis SWOT kuantitatif bertujuan untuk menentukan strategi terbaik yang dapat diambil dan digunakan oleh perusahaan dalam rangka bertahan dan berkompetisi di industri tertentu.hasil analisis faktor internal bahwa jsc memiliki kekuatan yang sangat besar dengan adanya kualitas atraksi yang baik serta menarik dan juga ketersediaan sarana transportasi yang sangat membantu pengunjung untuk datang ke venue, hasil faktor eksternal yang diidentifikasi memberikan hasil bahwa adanya peluang yang sangat tinggi bagi Jakabaring Sport City yaitu adanya dukungan pemerintah dengan memberikan fasilitas prokes pada venue Jakabaring Sport City membuat poster prokes yang tersebar merata disekitar venue Jakabaring Sport City, terutama disekitar venue yang menjadi titik kumpul terbanyak pengunjung, seperti di cafetaria, danau, dan lokasi lainnya, memberikan poster tulisan di toilet tentang aturan-aturan yang berlaku ditoilet seperti, jangan membuang sampah kotoran dikloset, jangan membuang tisu sembarang, dan peraturan lain yang behubungan tentang terjaganya kebersihan toilet

Relationship between estrogen receptor α location and gene induction reveals the importance of downstream sites and cofactors

BACKGROUND: To understand cancer-related modifications to transcriptional programs requires detailed knowledge about the activation of signal-transduction pathways and gene expression programs. To investigate the mechanisms of target gene regulation by human estrogen receptor alpha (hERalpha), we combine extensive location and expression datasets with genomic sequence analysis. In particular, we study the influence of patterns of DNA occupancy by hERalpha on expression phenotypes. RESULTS: We find that strong ChIP-chip sites co-localize with strong hERalpha consensus sites and detect nucleotide bias near hERalpha sites. The localization of ChIP-chip sites relative to annotated genes shows that weak sites are enriched near transcription start sites, while stronger sites show no positional bias. Assessing the relationship between binding configurations and expression phenotypes, we find binding sites downstream of the transcription start site (TSS) to be equally good or better predictors of hERalpha-mediated expression as upstream sites. The study of FOX and SP1 cofactor sites near hERalpha ChIP sites shows that induced genes frequently have FOX or SP1 sites. Finally we integrate these multiple datasets to define a high confidence set of primary hERalpha target genes. CONCLUSION: Our results support the model of long-range interactions of hERalpha with the promoter-bound cofactor SP1 residing at the promoter of hERalpha target genes. FOX motifs co-occur with hERalpha motifs along responsive genes. Importantly we show that the spatial arrangement of sites near the start sites and within the full transcript is important in determining response to estrogen signaling

ANALISIS PENENTUAN LOKASI RUMAH SAKIT TIPE C BARU MENGGUNAKAN METODE ANALYTICAL HIERARCHY PROCESS (AHP) DI KABUPATEN SUMEDANG

Laju pertumbuhan penduduk yang terus meningkat berjalan seiringan dengan permintaan masyarakat pada suatu fasilitas pelayanan di bidang kesehatan, khususnya rumah sakit. Kabupaten Sumedang merupakan salah satu wilayah di Provinsi Jawa Barat, Indonesia yang memiliki jumlah penduduk cukup tinggi. Namun berdasarkan standar rasio tempat tidur rumah sakit dengan jumlah penduduk 1:1.000 yang dirilis oleh Kementerian Kesehatan, Kabupaten Sumedang belum memenuhi standar rasio tersebut. Penelitian ini bertujuan untuk menganalisis kondisi sebaran rumah sakit eksisting dan menentukan alternatif lokasi rumah sakit tipe C baru yang ideal. Metode yang digunakan adalah metode Sistem Informasi Geografis dengan pembobotan AHP (Analytical Hierarchy Process). Teknik analisis data berupa analisis spasial deskriptif, network analyst service area dan overlay. Parameter penentuan lokasi rumah sakit baru dalam penelitian ini adalah penggunaan lahan, kemiringan lereng, jaringan jalan, kepadatan penduduk, daerah potensi banjir, dan daerah potensi longsor. Hasil penelitian menunjukan bahwa kondisi sebaran rumah sakit eksisting mampu menjangkau 13 Kecamatan dari 26 Kecamatan di Kabupaten Sumedang berdasarkan radius 10 km. Alternatif lokasi rumah sakit baru terbagi menjadi lima kelas yakni klasifikasi sangat tidak sesuai tertinggi berada di Kecamatan Buahdua dengan luas 73,27 km², klasifikasi tidak sesuai tertinggi berada di Kecamatan Jatigede dengan luas 47,74 km², klasifikasi agak sesuai tertinggi berada di Kecamatan Buahdua dengan luas 34,63 km², klasifikasi sesuai tertinggi berada di Kecamatan Sumedang Utara dengan luas 11,33 km², dan klasifikasi sangat sesuai tertinggi berada di Kecamatan Jatinangor dengan luas 6,83 km². Penelitian ini bermanfaat bagi masyarakat, pihak swasta, hingga pemerintah yang berkaitan dengan perencanaan pembangunan rumah sakit baru di suatu daerah. The increase of population grows together alongside demands for health related facilities, especially hospitals. Sumedang is a regency in West Java Province, Indonesia, that has a pretty dense population. Based on standard ratio of 1:1,000 hospitals to population which was released by Ministry of Health, Sumedang Regency has not meet the requirements yet. The objectives of this research are to analyze existing hospitals distribution condition and to consider some alternative locations for new ideal type C hospitals. Methods that are used for this research are Geographic Information System (GIS) concentrating on Analytical Hierarchy Proccess (AHP). These data are analyzed with spatial descriptive technique, network analyst service area, and overlay technique. Hospitals that were observed were picked under these parameters; (1) the land use, (2) the slope, (3) the road network, (4) population density, (5) potential flooding areas, and (6) potential landslide areas. Result shows that existing hospitals in current distribution would be able to provide care to 14 out of 26 districts in Sumedang within 10 kilometers radius. Alternative locations for new hospitals are divided into 5 classes; (1) highest very unsuitable, located in Buahdua District with area of 73.27 km², (2) highest unsuitable, located in Jatigede District with area of 47.74 km², (3) highest moderately suitable, located in Buahdua District with area of 34.63 km², (4) highest suitable, located in North Sumedang District with area of 11.33 km², and (5) highest very suitable, located in Jatinangor District with area of 6.83 km². This research is expected to be helpful for the community, including all kind of providers and caterers for the hospitals. Also to give some new perspectives regarding new hospital construction planning for the government officials

IS ACFTA A PROPER STRATEGY OF SUSTAINABLE POVERTY ALLEVIATION?: PROOF FROM THE DEPLETION OF SAVING RATE

The outcome of Regional Free Trade Area (R-FTA) still remains a conundrum. Regional free trade area (R-FTA) is one of the manifestations of the economy integration phenomenon. R-FTA brings many pros and cons to the economists. It allows better allocation of resources especially by eliminating tariffs, thus making people have higher purchasing power for goods. While the increase of purchasing power is good for growth engine and poverty alleviation progress, this paper proves that there is potency for the agreement to be detrimental in the long run. The main focus in this paper is the potential impact of ACFTA to the saving rate as the shock buffer for the poor in time of recessions and crises, where purchasing power decreases significantly. We view the ACFTA impact through the series of net import, defined as the difference between imports from export. We use Dynamic Panel Data (DPD) to estimate the impact of net import to the saving rate, assuming that there is a dynamic relationship between saving rate and its lagged value. The estimation result proves that there is a negative relationship between import and the saving per capita, which indicates the consumptive behavior of ASEAN people under high import. Moreover, the dynamic relationship shows that saving per capita is not persistent, meaning that the saving rate will be decreased gradually. Therefore, we can expect that in the long rung, the savings will be depleted into nothing if we keep letting the import flooded domestic market without imposing any pre-emptive and reactive policies. This paper provides a set of historical estimation of the potential impact of ACFTA on saving rate and its policy implication to endure the impact. JEL Classification Code: E38, F15 Keywords: Free Trade, Poverty Alleviation, Saving Behavio

APAKAH ACFTA MERUPAKAN STRATEGI YANG TEPAT UNTUK PENUNTASAN KEMISKINAN YANG BERKESINAMBUNGAN?: BUKTI DARI PENURUNAN TINGKAT SIMPANAN

The outcome of Regional Free Trade Area (R-FTA) still remains a conundrum. Regional free trade area (R-FTA) is one of the manifestations of the economy integration phenomenon. R-FTA brings many pros and cons to the economists. It allows better allocation of resources especially by eliminating tariffs, thus making people have higher purchasing power for goods. While the increase of purchasing power is good for growth engine and poverty alleviation progress, this paper proves that there is potency for the agreement to be detrimental in the long run. The main focus in this paper is the potential impact of ACFTA to the saving rate as the shock buffer for the poor in time of recessions and crises, where purchasing power decreases significantly. We view the ACFTA impact through the series of net import, defined as the difference between imports from export. We use Dynamic Panel Data (DPD) to estimate the impact of net import to the saving rate, assuming that there is a dynamic relationship between saving rate and its lagged value. The estimation result proves that there is a negative relationship between import and the saving per capita, which indicates the consumptive behavior of ASEAN people under high import. Moreover, the dynamic relationship shows that saving per capita is not persistent, meaning that the saving rate will be decreased gradually. Therefore, we can expect that in the long rung, the savings will be depleted into nothing if we keep letting the import flooded domestic market without imposing any pre-emptive and reactive policies. This paper provides a set of historical estimation of the potential impact of ACFTA on saving rate and its policy implication to endure the impact. JEL Classification Code: E38, F15 Keywords: Free Trade, Poverty Alleviation, Saving Behavio

A single-array preprocessing method for estimating full-resolution raw copy numbers from all Affymetrix genotyping arrays including GenomeWideSNP 5 & 6

Motivation: High-resolution copy-number (CN) analysis has in recent years gained much attention, not only for the purpose of identifying CN aberrations associated with a certain phenotype, but also for identifying CN polymorphisms. In order for such studies to be successful and cost effective, the statistical methods have to be optimized. We propose a single-array preprocessing method for estimating full-resolution total CNs. It is applicable to all Affymetrix genotyping arrays, including the recent ones that also contain non-polymorphic probes. A reference signal is only needed at the last step when calculating relative CNs

Low E2F1 transcript levels are a strong determinant of favorable breast cancer outcome

INTRODUCTION: We investigated whether mRNA levels of E2F1, a key transcription factor involved in proliferation, differentiation and apoptosis, could be used as a surrogate marker for the determination of breast cancer outcome. METHODS: E2F1 and other proliferation markers were measured by quantitative RT-PCR in 317 primary breast cancer patients from the Stiftung Tumorbank Basel. Correlations to one another as well as to the estrogen receptor and ERBB2 status and clinical outcome were investigated. Results were validated and further compared with expression-based prognostic profiles using The Netherlands Cancer Institute microarray data set reported by Fan and colleagues. RESULTS: E2F1 mRNA expression levels correlated strongly with the expression of other proliferation markers, and low values were mainly found in estrogen receptor-positive and ERBB2-negative phenotypes. Patients with low E2F1-expressing tumors were associated with favorable outcome (hazard ratio = 4.3 (95% confidence interval = 1.8-9.9), P = 0.001). These results were consistent in univariate and multivariate Cox analyses, and were successfully validated in The Netherlands Cancer Institute data set. Furthermore, E2F1 expression levels correlated well with the 70-gene signature displaying the ability of selecting a common subset of patients at good prognosis. Breast cancer patients' outcome was comparably predictable by E2F1 levels, by the 70-gene signature, by the intrinsic subtype gene classification, by the wound response signature and by the recurrence score. CONCLUSION: Assessment of E2F1 at the mRNA level in primary breast cancer is a strong determinant of breast cancer patient outcome. E2F1 expression identified patients at low risk of metastasis irrespective of the estrogen receptor and ERBB2 status, and demonstrated similar prognostic performance to different gene expression-based predictors