The completion of the Human Genome Project combined with the development of microarray technology and recent advances in mathematical biology have set the stage for the genome-wide discovery of differential gene expression between any biological samples from any living system. The term discovery implies the extrapolation of data without the confound of pre-existing biases. This laboratory has developed a mathematical solution for discovering highly specific states of genetic expression between genetic samples (up-or down-regulated). The false discovery rate of the algorithm for microarrays that contain 19,200 CDNAs is Ͻ 0.001%. 1 To explore the idea that genomic expression discovery predicts pathways and functions behind the biological phenotypes of living systems, we compare a tumor to its normal host organ. The expression data accurately predict activation of signaling pathways and propose that unbalanced opposing genetic functions create "aberrant" phenotypes. In addition, known molecular interactions reveal a rich network of stimulatory and inhibitory genetic interconnections.We use microarrays containing 19,200 cDNAs to profile gene expression in 10 meningiomas versus normal brain. Meningiomas are compared with normal brain, its host organ, because both tissue types contain non-tumor cells such as blood vessels and cells of lymphocytic lineage. Meningiomas comprise 15-20% of all primary intracranial tumors. They are abundantly vascular, tend to bleed during surgery, and often show ectopic calcification on computed tomagraphic (CT) scanning. Multiple meningiomas occur in association with a mutated neurofibromatosis type II tumor suppressor gene, known as merlin or schwannomin. Merlin protein appears to stabilize F-actin (2-4). Normal brain RNA was pooled from the occipital lobes of four individuals with no known neurological disease whose brains were frozen less than 3 h postmortem. EXPERIMENTAL PROCEDURESReagents-Information on the antibodies used may be obtained from the corresponding web sites: anti-␤-catenin, www.upstatebiotech.com; anti-glyceraldehydes-3-phosphate dehydrogenase (G3PDH), www. trevigen.com.; anti-Akt, 2 anti-phospho-Akt (Ser-473), anti-p44/42 MAP kinase (ERK), and anti-phospho-p44/p42 Map kinase (Thr-202/Tyr-204, ERK-P), www.cellsignal.com.Tumors-Patients signed informed consents, and the study is approved by the Institutional Review Boards of Rush University and Cook County Hospital. Tumor samples are frozen in liquid nitrogen in the operating room. The quality of RNA is assayed by gel electrophoresis; only high quality reference and sample RNAs are processed.Microarray Experiments-All total RNA samples are analyzed in reference to a single standard obtained by pooling RNA from human occipital lobes. The latter are harvested and pooled from four individuals with no known neurological disease whose brains were frozen less than 3 h postmortem. Total RNA (5-10 g) is reverse-transcribed and the cDNA products labeled by the amino-allyl method with switching of probes between sample and refere...

The soil microbiome is important for the functioning of terrestrial ecosystems. However, the impacts of climate on taxonomic and functional diversity of soil microbiome are not well understood. A precipitation gradient along regional scale transects may offer a model setting for understanding the effect of climate on the composition and function of the soil microbiome. Here, we compared taxonomic and functional attributes of soil microorganisms in arid, semiarid, Mediterranean, and humid Mediterranean climatic conditions of Israel using shotgun metagenomic sequencing. We hypothesized that there would be a distinct taxonomic and functional soil community for each precipitation zone, with arid environments having lower taxonomic and functional diversity, greater relative abundance of stress response and sporulation-related genes, and lower relative abundance of genes related to nutrient cycling and degradation of complex organic compounds. As hypothesized, our results showed a distinct taxonomic and functional community in each precipitation zone, revealing differences in soil taxonomic and functional selection in the different climates. Although the taxonomic diversity remained similar across all sites, the functional diversity was-as hypothesized-lower in the arid environments, suggesting that functionality is more constrained in "extreme" environments. Also, with increasing aridity, we found a significant increase in genes related to dormancy/sporulation and a decrease in those related to nutrient cycling (genes related to nitrogen, potassium, and sulfur metabolism), respectively. However, relative abundance of genes related to stress response were lower in arid soils. Overall, these results indicate that climatic conditions play an important role in shaping taxonomic and functional attributes of soil microbiome. These findings have important implications for understanding the impacts of climate change (e.g., precipitation change) on structure and function of the soil microbiome.

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