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The characterization of cancer genomes has provided insight into somatically altered genes across tumors, transformed our understanding of cancer biology, and enabled tailoring of therapeutic strategies. However, the function of most cancer alleles remains mysterious, and many cancer features transcend their genomes. Consequently, tumor genomic characterization does not influence therapy for most patients. Approaches to understand the function and circuitry of cancer genes provide complementary approaches to elucidate both oncogene and non-oncogene dependencies. Emerging work indicates that the diversity of therapeutic targets engendered by non-oncogene dependencies is much larger than the list of recurrently mutated genes. Here we describe a framework for this expanded list of cancer targets, providing novel opportunities for clinical translation.

The characterization of cancer genomes has provided insight into somatically altered genes across tumors, transformed our understanding of cancer biology, and enabled tailoring of therapeutic strategies. However, the function of most cancer alleles remains mysterious, and many cancer features transcend their genomes. Consequently, tumor genomic characterization does not influence therapy for most patients. Approaches to understand the function and circuitry of cancer genes provide complementary approaches to elucidate both oncogene and non-oncogene dependencies. Emerging work indicates that the diversity of therapeutic targets engendered by non-oncogene dependencies is much larger than the list of recurrently mutated genes. Here we describe a framework for this expanded list of cancer targets, providing novel opportunities for clinical translation.

The characterization of cancer genomes has provided insight into somatically altered genes across tumors, transformed our understanding of cancer biology, and enabled tailoring of therapeutic strategies. However, the function of most cancer alleles remains mysterious, and many cancer features transcend their genomes. Consequently, tumor genomic characterization does not influence therapy for most patients. Approaches to understand the function and circuitry of cancer genes provide complementary approaches to elucidate both oncogene and non-oncogene dependencies. Emerging work indicates that the diversity of therapeutic targets engendered by non-oncogene dependencies is much larger than the list of recurrently mutated genes. Here we describe a framework for this expanded list of cancer targets, providing novel opportunities for clinical translation.

We can now routinely identify coding variants within individual human genomes. A pressing challenge is to determine which variants disrupt the function of disease-associated genes. Both experimental and computational methods exist to predict pathogenicity of human genetic variation. However, a systematic performance comparison between them has been lacking. Therefore, we developed and exploited a panel of 26 yeast-based functional complementation assays to measure the impact of 179 variants (101 disease-and 78 non-disease-associated variants) from 22 human disease genes. Using the resulting reference standard, we show that experimental functional assays in a 1-billion-year diverged model organism can identify pathogenic alleles with significantly higher precision and specificity than current computational methods.

We can now routinely identify coding variants within individual human genomes. A pressing challenge is to determine which variants disrupt the function of disease-associated genes. Both experimental and computational methods exist to predict pathogenicity of human genetic variation. However, a systematic performance comparison between them has been lacking. Therefore, we developed and exploited a panel of 26 yeast-based functional complementation assays to measure the impact of 179 variants (101 disease-and 78 non-disease-associated variants) from 22 human disease genes. Using the resulting reference standard, we show that experimental functional assays in a 1-billion-year diverged model organism can identify pathogenic alleles with significantly higher precision and specificity than current computational methods.

While alternative splicing is known to diversify the functional characteristics of some genes, the extent to which protein isoforms globally contribute to functional complexity on a proteomic scale remains unknown. To address this systematically, we cloned full-length open reading frames of alternatively spliced transcripts for a large number of human genes and used protein-protein interaction profiling to functionally compare hundreds of protein isoform pairs. The majority of isoform pairs share less than 50% of their interactions. In the global context of interactome network maps, alternative isoforms tend to behave like distinct proteins rather than minor variants of each other. Interaction partners specific to alternative isoforms tend to be expressed in a highly tissue-specific manner and belong to distinct functional modules. Our strategy, applicable to other functional characteristics, reveals a widespread expansion of protein interaction capabilities through alternative splicing and suggests that many alternative "isoforms'' are functionally divergent (i.e., "functional alloforms'').

We can now routinely identify coding variants within individual human genomes. A pressing challenge is to determine which variants disrupt the function of disease-associated genes. Both experimental and computational methods exist to predict pathogenicity of human genetic variation. However, a systematic performance comparison between them has been lacking. Therefore, we developed and exploited a panel of 26 yeast-based functional complementation assays to measure the impact of 179 variants (101 disease-and 78 non-disease-associated variants) from 22 human disease genes. Using the resulting reference standard, we show that experimental functional assays in a 1-billion-year diverged model organism can identify pathogenic alleles with significantly higher precision and specificity than current computational methods.

We can now routinely identify coding variants within individual human genomes. A pressing challenge is to determine which variants disrupt the function of disease-associated genes. Both experimental and computational methods exist to predict pathogenicity of human genetic variation. However, a systematic performance comparison between them has been lacking. Therefore, we developed and exploited a panel of 26 yeast-based functional complementation assays to measure the impact of 179 variants (101 disease-and 78 non-disease-associated variants) from 22 human disease genes. Using the resulting reference standard, we show that experimental functional assays in a 1-billion-year diverged model organism can identify pathogenic alleles with significantly higher precision and specificity than current computational methods.

We can now routinely identify coding variants within individual human genomes. A pressing challenge is to determine which variants disrupt the function of disease-associated genes. Both experimental and computational methods exist to predict pathogenicity of human genetic variation. However, a systematic performance comparison between them has been lacking. Therefore, we developed and exploited a panel of 26 yeast-based functional complementation assays to measure the impact of 179 variants (101 disease-and 78 non-disease-associated variants) from 22 human disease genes. Using the resulting reference standard, we show that experimental functional assays in a 1-billion-year diverged model organism can identify pathogenic alleles with significantly higher precision and specificity than current computational methods.

Chopped and moist paddy straw was pretreated with Fusarium sp. to enhance its digestibility and biogas production. The potential of microbial pretreatment of paddy straw was investigated at regular interval of 5, 10, 15 and 20 days by determining the change in Chemical composition of paddy straw like cellulose, hemicellulose, lignin and silica contents. The pretreated straw was used for biogas production in 2l capacity biogas digesters. Results indicate that the cellulose, hemicellulose, lignin and silica contents decreased by 17.2%, 3.4%, 27.1% & 16.5% respectively. Biogas production also increased by 53.8% in 10 days pretreated samples. The significantly higher reduction of silica along with lignin content in the pretreated straw indicates that removal of silica by Fusarium sp. might be more responsible for increasing paddy straw digestibility and biogas production.

Chopped and moist paddy straw was pretreated with Fusarium sp. to enhance its digestibility and biogas production. The potential of microbial pretreatment of paddy straw was investigated at regular interval of 5, 10, 15 and 20 days by determining the change in Chemical composition of paddy straw like cellulose, hemicellulose, lignin and silica contents. The pretreated straw was used for biogas production in 2l capacity biogas digesters. Results indicate that the cellulose, hemicellulose, lignin and silica contents decreased by 17.2%, 3.4%, 27.1% & 16.5% respectively. Biogas production also increased by 53.8% in 10 days pretreated samples. The significantly higher reduction of silica along with lignin content in the pretreated straw indicates that removal of silica by Fusarium sp. might be more responsible for increasing paddy straw digestibility and biogas production.

Chopped and moist paddy straw was pretreated with Fusarium sp. to enhance its digestibility and biogas production. The potential of microbial pretreatment of paddy straw was investigated at regular interval of 5, 10, 15 and 20 days by determining the change in Chemical composition of paddy straw like cellulose, hemicellulose, lignin and silica contents. The pretreated straw was used for biogas production in 2l capacity biogas digesters. Results indicate that the cellulose, hemicellulose, lignin and silica contents decreased by 17.2%, 3.4%, 27.1% & 16.5% respectively. Biogas production also increased by 53.8% in 10 days pretreated samples. The significantly higher reduction of silica along with lignin content in the pretreated straw indicates that removal of silica by Fusarium sp. might be more responsible for increasing paddy straw digestibility and biogas production.

Chopped and moist paddy straw was pretreated with Fusarium sp. to enhance its digestibility and biogas production. The potential of microbial pretreatment of paddy straw was investigated at regular interval of 5, 10, 15 and 20 days by determining the change in Chemical composition of paddy straw like cellulose, hemicellulose, lignin and silica contents. The pretreated straw was used for biogas production in 2l capacity biogas digesters. Results indicate that the cellulose, hemicellulose, lignin and silica contents decreased by 17.2%, 3.4%, 27.1% & 16.5% respectively. Biogas production also increased by 53.8% in 10 days pretreated samples. The significantly higher reduction of silica along with lignin content in the pretreated straw indicates that removal of silica by Fusarium sp. might be more responsible for increasing paddy straw digestibility and biogas production.

Chopped and moist paddy straw was pretreated with Fusarium sp. to enhance its digestibility and biogas production. The potential of microbial pretreatment of paddy straw was investigated at regular interval of 5, 10, 15 and 20 days by determining the change in Chemical composition of paddy straw like cellulose, hemicellulose, lignin and silica contents. The pretreated straw was used for biogas production in 2l capacity biogas digesters. Results indicate that the cellulose, hemicellulose, lignin and silica contents decreased by 17.2%, 3.4%, 27.1% & 16.5% respectively. Biogas production also increased by 53.8% in 10 days pretreated samples. The significantly higher reduction of silica along with lignin content in the pretreated straw indicates that removal of silica by Fusarium sp. might be more responsible for increasing paddy straw digestibility and biogas production.

Chopped and moist paddy straw was pretreated with Fusarium sp. to enhance its digestibility and biogas production. The potential of microbial pretreatment of paddy straw was investigated at regular interval of 5, 10, 15 and 20 days by determining the change in Chemical composition of paddy straw like cellulose, hemicellulose, lignin and silica contents. The pretreated straw was used for biogas production in 2l capacity biogas digesters. Results indicate that the cellulose, hemicellulose, lignin and silica contents decreased by 17.2%, 3.4%, 27.1% & 16.5% respectively. Biogas production also increased by 53.8% in 10 days pretreated samples. The significantly higher reduction of silica along with lignin content in the pretreated straw indicates that removal of silica by Fusarium sp. might be more responsible for increasing paddy straw digestibility and biogas production.

Chopped and moist paddy straw was pretreated with Fusarium sp. to enhance its digestibility and biogas production. The potential of microbial pretreatment of paddy straw was investigated at regular interval of 5, 10, 15 and 20 days by determining the change in Chemical composition of paddy straw like cellulose, hemicellulose, lignin and silica contents. The pretreated straw was used for biogas production in 2l capacity biogas digesters. Results indicate that the cellulose, hemicellulose, lignin and silica contents decreased by 17.2%, 3.4%, 27.1% & 16.5% respectively. Biogas production also increased by 53.8% in 10 days pretreated samples. The significantly higher reduction of silica along with lignin content in the pretreated straw indicates that removal of silica by Fusarium sp. might be more responsible for increasing paddy straw digestibility and biogas production.

Chopped and moist paddy straw was pretreated with Fusarium sp. to enhance its digestibility and biogas production. The potential of microbial pretreatment of paddy straw was investigated at regular interval of 5, 10, 15 and 20 days by determining the change in Chemical composition of paddy straw like cellulose, hemicellulose, lignin and silica contents. The pretreated straw was used for biogas production in 2l capacity biogas digesters. Results indicate that the cellulose, hemicellulose, lignin and silica contents decreased by 17.2%, 3.4%, 27.1% & 16.5% respectively. Biogas production also increased by 53.8% in 10 days pretreated samples. The significantly higher reduction of silica along with lignin content in the pretreated straw indicates that removal of silica by Fusarium sp. might be more responsible for increasing paddy straw digestibility and biogas production.