Maximilian Miller

Rutgers, The State University of New Jersey | Rutgers · Department of Biochemistry and Microbiology

Background The Critical Assessment of Genome Interpretation (CAGI) aims to advance the state-of-the-art for computational prediction of genetic variant impact, particularly where relevant to disease. The five complete editions of the CAGI community experiment comprised 50 challenges, in which participants made blind predictions of phenotypes from g...

Infertility is a major reproductive health issue that affects about 12% of women of reproductive age in the United States. Aneuploidy in eggs accounts for a significant proportion of early miscarriage and in vitro fertilization failure. Recent studies have shown that genetic variants in several genes affect chromosome segregation fidelity and predi...

Biological redox reactions drive planetary biogeochemical cycles. Using a novel, structure-guided sequence analysis of proteins, we explored the patterns of evolution of enzymes responsible for these reactions. Our analysis reveals that the folds that bind transition metal–containing ligands have similar structural geometry and amino acid sequences...

Non-synonymous Single Nucleotide Variants (nsSNVs), resulting in single amino acid variants (SAVs), are important drivers of evolutionary adaptation across the tree of life. Humans carry on average over 10,000 SAVs per individual genome, many of which likely have little to no impact on the function of the protein they affect. Experimental evidence...

Microbes active in extreme cold are not as well explored as those of other extreme environments. Studies have revealed a substantial microbial diversity and identified cold‐specific microbiome molecular functions. We analyzed the metagenomes and metatranscriptomes of 20 snow samples collected in early and late spring in Svalbard, Norway using mi‐fa...

The past two decades of analytical efforts have highlighted how much more remains to be learned about the human genome and, particularly, its complex involvement in promoting disease development and progression. While numerous computational tools exist for the assessment of the functional and pathogenic effects of genome variants, their precision i...

Motivation: The applicability and reproducibility of bioinformatics methods and results often depend on the structure and software architecture of their development. Exponentially growing data sets require ever more optimization and performance with conventional computing capacities lacking this process. This creates a large overhead for software d...

Mercury (Hg) is a highly toxic and widely distributed heavy metal which some Bacteria and Archaea detoxify by the reduction of ionic Hg (Hg[II]) to the elemental volatile form, Hg(0). This activity is specified by the mer operon. The mer operon of the deeply‐branching thermophile Thermus thermophilus HB27 encodes for, an O‐acetyl‐L‐homoacetylserine...

Microbes active in extremely cold environments are not as well explored as those of other extreme environments. Studies have revealed a substantial microbial diversity and identified cold-specific microbiome molecular functions. We analyzed the metagenomes and metatranscriptomes of twenty snow samples collected during early and late spring in Svalb...

Background: Accumulating evidence suggests that the human microbiome impacts individual and public health. City subway systems are human-dense environments, where passengers often exchange microbes. The MetaSUB project participants collected samples from subway surfaces in different cities and performed metagenomic sequencing. Previous studies foc...

Evaluating the impact of non-synonymous genetic variants is essential for uncovering disease associations and mechanisms of evolution. An in-depth understanding of sequence changes is also fundamental for synthetic protein design and stability assessments. However, the variant effect predictor performance gain observed in recent years has not kept...

Background: After years of concentrated research efforts, the exact cause of Crohn's disease (CD) remains unknown. Its accurate diagnosis, however, helps in management and preventing the onset of disease. Genome-wide association studies have identified 241 CD loci, but these carry small log odds ratios and are thus diagnostically uninformative. M...

The recent years have seen a drastic increase in the amount of available genomic sequences. Alongside this explosion, hundreds of computational tools were developed to assess the impact of observed genetic variation. Critical Assessment of Genome Interpretation (CAGI) provides a platform to evaluate the performance of these tools in experimentally...

The CAGI‐5 PCM1 challenge aimed to predict the effect of 38 transgenic human missense mutations in the Pericentriolar Material 1 (PCM1) protein implicated in schizophrenia. Participants were provided with 16 benign variants (negative controls), 10 hypomorphic, and 12 loss of function variants. Six groups participated and were asked to predict the p...

The availability of disease‐specific genomic data is critical for developing new computational methods that predict the pathogenicity of human variants and advance the field of precision medicine. However, the lack of gold standards to properly train and benchmark such methods is one of the greatest challenges in the field. In response to this chal...

Thermodynamic stability is a fundamental property shared by all proteins. Changes in stability due to mutation are a widespread molecular mechanism in genetic diseases. Methods for the prediction of mutation‐induced stability change have typically been developed and evaluated on incomplete and/or biased data sets. As part of the Critical Assessment...

Motivation: Evaluating the impact of non-synonymous genetic variants is essential for uncovering disease associations. Understanding the corresponding changes in protein sequences can also help with synthetic protein design and stability assessments. Even though hundreds of computational approaches addressing this task exist, and more are being dev...

Microbial functional diversification is driven by environmental factors, i.e. microorganisms inhabiting the same environmental niche tend to be more functionally similar than those from different environments. In some cases, even closely phylogenetically related microbes differ more across environments than across taxa. While microbial similarities...

The above paper was corrected online, as the Authors noticed an error in the author names.

The vast majority of microorganisms on Earth reside in often-inseparable environment-specific communities-microbiomes. Meta-genomic/-transcriptomic sequencing could reveal the otherwise inaccessible functionality of microbiomes. However, existing analytical approaches focus on attributing sequencing reads to known genes/genomes, often failing to ma...

With the advent of modern day high-throughput technologies, the bottleneck in biological discovery has shifted from the cost of doing experiments to that of analyzing results. clubber is our automated cluster-load balancing system developed for optimizing these "big data" analyses. Its plug-and-play framework encourages re-use of existing solutions...

Microbial functional diversification is driven by environmental factors, i.e. microorganisms inhabiting the same environmental niche tend to be more functionally similar than those from different environments. In some cases, even closely phylogenetically related microbes differ more across environments than across taxa. While microbial similarities...

Many computational approaches exist for predicting the effects of amino acid substitutions. Here, we considered whether the protein sequence position class – rheostat or toggle – affects these predictions. The classes are defined as follows: experimentally evaluated effects of amino acid substitutions at toggle positions are binary, while rheostat...