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This technology includes a novel computational algorithm and software implementation to map and display biological pathways and their relationship on the surface of a globe in a three-dimensional space. Currently, biological pathways and genes are represented as two-dimensional networks, which is not effective for displaying complicated relationships between pathways and genes.

Methylmalonic Acidemia (MMA) is a metabolic disorder characterized by increased acidity in the blood and tissues due to toxic accumulation of protein and fat by-products resulting in seizures, strokes, and chronic kidney failure. A significant portion of MMA cases stem from a deficiency in a key mitochondrial enzyme, methylmalonyl-CoA mutase (MUT), required to break down amino acids and lipids. Currently, there are no treatments for MMA and the disease is managed primarily with dietary restriction of amino acid precursors and liver-kidney transplantation in severe cases.

Isolated Methylmalonic Acidemia (MMA) comprises a relatively common and heterogeneous group of inborn errors of metabolism. Most affected individuals display severe multisystemic disease characterized by metabolic instability, chronic renal disease, and neurological complications. Patients with the cobalamin A (cblA) subtype of MMA can have variable presentations, spanning the full spectrum of MMA associated symptoms and pathology, yet always harbor an element of clinical and biochemical responsiveness to injectable vitamin B12.

Cobalamin C deficiency (cblC) is the most common inborn error of intracellular cobalamin metabolism and is caused by mutations in MMACHC, a gene responsible for processing and trafficking dependent enzymes: intracellular cobalamin, resulting in elevated methylmalonic acid and homocysteine and methionine deficiency. Disease manifestations include growth failure, anemia, cardial defects and progressive blindness.

Isolated Methylmalonic Acidemia (MMA) and the related disorder Propionic Acidemia (PA) comprise a relatively common and heterogeneous group of inborn errors of metabolism. NHGRI scientist discovered that in isolated MMA, a novel inhibitory PTM, methylmalonyllysine, is generated and inactivates protein targets through the failure of SIRT-mediated deacylation, and identified a series of antibodies for PTM specificity.

Propionic acidemia (PA) is an autosomal recessive metabolic disorder caused by mutations in either PCCA or PCCB. The products of these genes form the alpha and beta subunits of the enzyme propionyl-Co A carboxylase (PCC), a critically important mitochondrial enzyme involved in the catabolism of branched chain amino acids. NHGRI scientist have developed new mouse models that more closely mimic the nature of mutations seen in patients, such as missense mutations, small insertion and deletions, splicing defects, and frameshift changes.

Cobalamin C deficiency (cblC), caused by mutations in MMACHC, is the most common inborn error of intracellular vitamin B12 metabolism. NHGRI scientist have generated a number of Mmachc knockout mouse models. The cblC mice present with early lethality, recapitulate the neurological phenotype seen in patients, and have enabled proof of concept testing with traditional hydroxocobalamin formulations and doses. The scientist have also developed a novel combination of hydroxo- and methylcobalamin, having superior performance to traditional hydroxocobalamin only treatment.

Isolated Methylmalonic Acidemia (MMA) comprises a relatively common and heterogeneous group of inborn errors of metabolism. In order to create mouse models of MMA to resemble the pathogenic mutations seen in patients, the NHGRI scientist used genome editing to generate new mutants of the Mmut allele -p.Pro207 _Lys210del. In order to create mouse models of MMA to resemble the pathogenic mutations seen in patients, the NHGRI scientist used genome editing to generate new mutants of Mmut allele -p.Pro207 _Lys210del. This allele recapitulates a 12-nucleotide deletion in exon 3 of Mmut.

Isolated Methylmalonic Acidemia (MMA) comprises a relatively common and heterogeneous group of inborn errors of metabolism. In order to create mouse models of MMA to resemble the pathogenic mutations seen in patients, the NHGRI scientist used genome editing to generate new mutants of Mmut allele -p.G715V. This allele recapitulates a missense mutation seen in multiple patients with the disorder. Of note and emphasis is the fact that there are no transgene cassettes or other alternations to the Mmut locus in these new mouse models.

Propionic acidemia (PA) is an autosomal recessive metabolic disorder caused by mutations in either Propionyl-CoA carboxylase alpha (PCCA) or Propionyl-CoA carboxylase beta (PCCB). The products of these genes form the alpha and beta subunits of the enzyme propionyl-Co A carboxylase (PCC), a critically important mitochondrial enzyme involved in the catabolism of branched chain amino acids.