International Business Machines Corporation

Thomas Jefferson University

Isidore Rigoutsos

Tien Huynh

Aris Floratos

Aristidis Floratos

Aristotelis Tsirigos

Kevin Charles Miranda

Peter Riek

Robert M Graham

Jiri Novotny

Aristeidis G Telonis

Alice Carolyn McHardy

Gustavo Alejandro Stolovitzky

Laxmi Priya Parida

Stanislav Polonsky

Andrea Califano

Tetsuo Shibuya

Phillipe Loher

B David Silverman

Eric Londin

Yuan Gao

A method of identifying a subject in need of therapeutic intervention to treat a disease or condi-tion or disease recurrence or disease progression comprising, isolating isomiRs or miRNAs from a sample obtained from the subject; and characterizing the isomiRs or miRNAs and their presence or absence in the sample to identify a signature, wherein when the signature is indicative of a di-agnosis of the disease then treatment of the subject is recommended.

Leveraging the presence or absence of miRNA isoforms for recommending therapy in cancer patients

Methods of treating a disease by leveraging positive and negative correlations between tRNA-derived fragments (tRF) and messenger RNA (mRNA) wherein said correlations can be used to establish a level of granularity that is specific to a disease of interest wherein said disease-specific positive and negative correlations can allow a level of therapeutic intervention that will be unprecedented because it will have been informed by three dimensions: at least one mRNA of interest; at least one tRF that are positively/negatively correlated with it; and, the identity of the disease in which one wishes to modulate the abundance of the at least one mRNA of interest.

Systems-level analysis of 32 TCGA cancers reveals disease-dependent tRNA fragmentation patterns and very selective associations with messenger RNAs and repeat elements

The present invention includes a method for analyzing RNA fragments. In one aspect, the present invention includes a method of identifying a subject in need of therapeutic intervention to treat a disease or condition, disease recurrence, or disease progression comprises characterizing the identity of rRNA fragments. The invention also includes diagnosing, identifying or monitoring a disease or condition, and a method for identifying rRNA fragments. The invention also includes diagnosing, identifying or monitoring a glaucoma in a subject in need thereof by characterizing the identity of rRNA or tRNA fragments.

Compositions and methods of using RNA fragments

Disclosed herein are novel compositions, methods, and systems for determining whether a subject has, or is at risk of developing, or is at a given stage of a condition afflicting a tissue of interest, or determining the tissue or cell provenance of a biological sample, based on expression level of one or more of the novel miRNA and isomiR sequences disclosed herein. The compositions, methods, and systems described herein can be used to diagnose a disease or disorder, or prognose a given stage and/or progression of the disease or disorder, or determine the identity of the tissue or cell in a sample. In some embodiments, the compositions, methods, and systems described herein can be used to develop a treatment for the disease or disorder. For example, in some embodiments, the novel miRNAs can be used as therapeutics for treatment of a disease or disorder.

Human miRNAs for use in diagnosis, prognosis, and therapy of human conditions and diseases

Sequences of ribonucleic acid interference molecules are provided. For example, in one aspect, at least one nucleic acid molecule comprising at least one of one or more precursor sequences having SEQ_ID NO: 1 through SEQ_ID NO: 3,197 and one or more corresponding mature sequences having SEQ_ID NO: 3,198 through SEQ_ID NO: 6,565 is provided. Techniques are also provided for regulating gene expression.

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Sequences of ribonucleic acid interference molecules are provided. For example, in one aspect, at least one nucleic acid molecule comprising at least one of one or more precursor sequences having SEQ_ID NO: 1 through SEQ_ID NO: 11,928 and one or more corresponding mature sequences having SEQ_ID NO: 11,929 through SEQ_ID NO: 24,555 is provided. Techniques are also provided for regulating gene expression.

A method for determining whether a nucleotide sequence contains a microRNA binding site and which microRNA will bind thereto is provided. For example, in one aspect of the invention, a method for determining whether a nucleotide sequence contains a microRNA binding site and which microRNA sequence will bind thereto is comprised of the following steps. One or more patterns are generated by processing a collection of known mature microRNA sequences. The reverse complement of each generated patter is then computed. One or more attributes are then assigned to the reverse complement of the one or more generated patterns. The one or more patterns that correspond to a reverse complement having one or more assigned attributes that satisfy at least one criterion are thereafter subselected. Each subselected pattern is then used to analyze the nucleotide sequence, such that a determination is made whether the nucleotide sequence contains a microRNA binding site and which microRNA sequence will bind thereto.

System and method for identification of microRNA target sites and corresponding targeting microRNA sequences

Ribonucleic acid interference molecules are provided. In one aspect of the invention, a method for regulating gene expression comprises the following step. At least one nucleic acid molecule comprising at least one of one or more precursor sequences having SEQ ID NO: 1 through SEQ ID NO: 103,948, each one of the precursor sequences containing one or more mature sequences having SEQ ID NO: 103,949 through SEQ ID NO: 230,447, is used to regulate the expression of one or more genes.

Ribonucleic acid interference molecules

A method and system are disclosed for matching input character sequences in a set of input patterns. The method comprises the steps of analyzing the set of input patterns, creating a pattern cluster look-up table (PCLT) based on said input patterns, and defining an offset value k. The PCLT is used to find, for each sequence s and offset k, a set of candidate patterns that can possibly match s, the set of candidate patterns is searched for patterns that match s, and all found matching patterns and sequences are reported.

Method and apparatus for matching of bracketed patterns in test strings

In one aspect of the invention, a method for regulating the expression of a transcript comprises using at least one interfering RNA molecule that binds to an area of transcript containing a region that corresponds to at least one sequence having SEQ ID NO: 1, the interfering RNA molecule regulating the expression of the transcript through post-transcriptional silencing. In another aspect, a method for regulating the expression of a transcript comprises at least one of the provided sequences having SEQ ID NO: 1 being used to design an interfering RNA molecule that contains a region that corresponds to the reverse complement of one or more sequences having SEQ ID NO: 1, the interfering molecule regulating, through post-transcriptional silencing, transcripts that contain the sequence having SEQ ID NO: 1.

Ribonucleic acid interference molecules and binding sites derived by analyzing intergenic and intronic regions of genomes

Techniques for linking non-coding and gene coding regions of a genome are provided. In one aspect, a method of determining associations between non-coding sequences and gene coding sequences in a genome of an organism comprises the following steps. At least one conserved region is identified from one or more non-coding sequences. Additional instances of the conserved region are located in the untranslated or amino acid coding regions of one or more genes in the organism under consideration, and the conserved region is associated with the one or more biological processes in which these one or more genes participate.

Techniques for linking non-coding and gene-coding deoxyribonucleic acid sequences and applications thereof

The relationship between an amino acid sequence of a protein and its three-dimensional structure is at the very core of structural biology and bioinformatics. The occurrence and conservation of non-canonical conformations is a 'local' phenomenon, i.e., non-canonical conformations are encoded intra-helically by short peptide sequences (heptapeptides at most). Effective descriptors can be formed for these short sequences employing training sets. Multiple, distinct patterns are created representing these sequences. A composite descriptor is formed by selecting from among the patterns discovered. The composite descriptor has a high level of sensitivity and specificity while, at the same time, a boosted signal-to-noise ratio.

Sequence pattern descriptors for transmembrane structural details

A method and system for determining whether a sequence fragment g is atypical with respect to a reference sequence G using compositional methods and including constructing a template from G and g respectively containing a sequence of characters for a comparison with one another, wherein a number of characters contained in the template exceeds two. For the case where the sequences at hand are genetic, the atypicality detection can be used to determine whether a given sequence fragment g is the result of a horizontal transfer event.

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Astoria, NY, United States of America

Isidore Rigoutsos