diff --git a/build.gradle b/build.gradle
index b29f8e3d8..ddd12a34d 100644
--- a/build.gradle
+++ b/build.gradle
@@ -42,6 +42,7 @@ dependencies {
     compile "gov.nih.nlm.ncbi:ngs-java:1.2.4"
 
     testCompile "org.testng:testng:6.9.9"
+    testCompile "com.google.jimfs:jimfs:1.1"
 }
 
 sourceCompatibility = 1.8
diff --git a/src/main/java/htsjdk/samtools/SamInputResource.java b/src/main/java/htsjdk/samtools/SamInputResource.java
index d76694eeb..c1ffb2dd4 100644
--- a/src/main/java/htsjdk/samtools/SamInputResource.java
+++ b/src/main/java/htsjdk/samtools/SamInputResource.java
@@ -29,6 +29,7 @@
 import htsjdk.samtools.seekablestream.SeekableStream;
 import htsjdk.samtools.seekablestream.SeekableStreamFactory;
 import htsjdk.samtools.sra.SRAAccession;
+import htsjdk.samtools.util.IOUtil;
 import htsjdk.samtools.util.Lazy;
 import htsjdk.samtools.util.RuntimeIOException;
 
@@ -366,8 +367,8 @@ public File asFile() {
     @Override
     public Path asPath() {
         try {
-            return Paths.get(urlResource.toURI());
-        } catch (URISyntaxException | IllegalArgumentException |
+            return IOUtil.getPath(urlResource.toExternalForm());
+        } catch (IOException | IllegalArgumentException |
             FileSystemNotFoundException | SecurityException e) {
             return null;
         }
diff --git a/src/main/java/htsjdk/samtools/seekablestream/SeekableStreamFactory.java b/src/main/java/htsjdk/samtools/seekablestream/SeekableStreamFactory.java
index fe8f42a56..ec8b9526e 100644
--- a/src/main/java/htsjdk/samtools/seekablestream/SeekableStreamFactory.java
+++ b/src/main/java/htsjdk/samtools/seekablestream/SeekableStreamFactory.java
@@ -23,6 +23,7 @@
  */
 package htsjdk.samtools.seekablestream;
 
+import htsjdk.samtools.util.IOUtil;
 import java.io.File;
 import java.io.IOException;
 import java.net.URL;
@@ -78,6 +79,8 @@ public SeekableStream getStreamFor(final String path) throws IOException {
                 return new SeekableFTPStream(new URL(path));
             } else if (path.startsWith("file:")) {
                 return new SeekableFileStream(new File(new URL(path).getPath()));
+            } else if (IOUtil.hasScheme(path)) {
+                return new SeekablePathStream(IOUtil.getPath(path));
             } else {
                 return new SeekableFileStream(new File(path));
             }
diff --git a/src/main/java/htsjdk/samtools/util/IOUtil.java b/src/main/java/htsjdk/samtools/util/IOUtil.java
index 07ae9006a..97d4d9cdc 100644
--- a/src/main/java/htsjdk/samtools/util/IOUtil.java
+++ b/src/main/java/htsjdk/samtools/util/IOUtil.java
@@ -48,14 +48,20 @@
 import java.io.Reader;
 import java.io.Writer;
 import java.net.MalformedURLException;
+import java.net.URI;
+import java.net.URISyntaxException;
 import java.net.URL;
 import java.nio.charset.Charset;
+import java.nio.file.FileSystemNotFoundException;
+import java.nio.file.FileSystems;
 import java.nio.file.Files;
 import java.nio.file.Path;
+import java.nio.file.Paths;
 import java.util.ArrayList;
 import java.util.Arrays;
 import java.util.Collection;
 import java.util.Collections;
+import java.util.HashMap;
 import java.util.LinkedList;
 import java.util.List;
 import java.util.Scanner;
@@ -943,4 +949,42 @@ public static String slurp(final InputStream is, final Charset charSet) {
 
         return output;
     }
+
+    /**
+     * Check if the given URI has a scheme.
+     *
+     * @param uriString the URI to check
+     * @return <code>true</code> if the given URI has a scheme, <code>false</code> if
+     * not, or if the URI is malformed.
+     */
+    public static boolean hasScheme(String uriString) {
+        try {
+            return new URI(uriString).getScheme() != null;
+        } catch (URISyntaxException e) {
+            return false;
+        }
+    }
+
+    /**
+     * Converts the given URI to a {@link Path} object. If the filesystem cannot be found in the usual way, then attempt
+     * to load the filesystem provider using the thread context classloader. This is needed when the filesystem
+     * provider is loaded using a URL classloader (e.g. in spark-submit).
+     *
+     * @param uriString the URI to convert
+     * @return the resulting {@code Path}
+     * @throws IOException an I/O error occurs creating the file system
+     */
+    public static Path getPath(String uriString) throws IOException {
+        URI uri = URI.create(uriString);
+        try {
+            // if the URI has no scheme, then treat as a local file, otherwise use the scheme to determine the filesystem to use
+            return uri.getScheme() == null ? Paths.get(uriString) : Paths.get(uri);
+        } catch (FileSystemNotFoundException e) {
+            ClassLoader cl = Thread.currentThread().getContextClassLoader();
+            if (cl == null) {
+                throw e;
+            }
+            return FileSystems.newFileSystem(uri, new HashMap<>(), cl).provider().getPath(uri);
+        }
+    }
 }
diff --git a/src/main/java/htsjdk/tribble/util/ParsingUtils.java b/src/main/java/htsjdk/tribble/util/ParsingUtils.java
index 2a88ed735..38cf8ab7f 100644
--- a/src/main/java/htsjdk/tribble/util/ParsingUtils.java
+++ b/src/main/java/htsjdk/tribble/util/ParsingUtils.java
@@ -23,6 +23,7 @@
  */
 package htsjdk.tribble.util;
 
+import htsjdk.samtools.util.IOUtil;
 import java.awt.Color;
 import java.io.File;
 import java.io.FileInputStream;
@@ -31,6 +32,7 @@
 import java.lang.reflect.Constructor;
 import java.net.MalformedURLException;
 import java.net.URL;
+import java.nio.file.Files;
 import java.util.ArrayList;
 import java.util.Arrays;
 import java.util.Collection;
@@ -83,6 +85,8 @@ public static InputStream openInputStream(String path)
 
         if (path.startsWith("http:") || path.startsWith("https:") || path.startsWith("ftp:")) {
             inputStream = getURLHelper(new URL(path)).openInputStream();
+        } else if (IOUtil.hasScheme(path)) {
+            inputStream = Files.newInputStream(IOUtil.getPath(path));
         } else {
             File file = new File(path);
             inputStream = new FileInputStream(file);
@@ -400,6 +404,8 @@ public static boolean resourceExists(String resource) throws IOException{
             }
             URLHelper helper = getURLHelper(url);
             return helper.exists();
+        } else if (IOUtil.hasScheme(resource)) {
+            return Files.exists(IOUtil.getPath(resource));
         } else {
             return (new File(resource)).exists();
         }
diff --git a/src/main/java/htsjdk/variant/vcf/AbstractVCFCodec.java b/src/main/java/htsjdk/variant/vcf/AbstractVCFCodec.java
index 16857b4e6..04887aeea 100644
--- a/src/main/java/htsjdk/variant/vcf/AbstractVCFCodec.java
+++ b/src/main/java/htsjdk/variant/vcf/AbstractVCFCodec.java
@@ -26,6 +26,7 @@
 package htsjdk.variant.vcf;
 
 import htsjdk.samtools.util.BlockCompressedInputStream;
+import htsjdk.samtools.util.IOUtil;
 import htsjdk.tribble.AsciiFeatureCodec;
 import htsjdk.tribble.Feature;
 import htsjdk.tribble.NameAwareCodec;
@@ -45,6 +46,8 @@
 import java.io.FileNotFoundException;
 import java.io.IOException;
 import java.io.InputStream;
+import java.nio.file.Files;
+import java.nio.file.Path;
 import java.util.ArrayList;
 import java.util.Arrays;
 import java.util.HashMap;
@@ -616,10 +619,11 @@ private static void parseSingleAltAllele(List<Allele> alleles, String alt, int l
 
     public static boolean canDecodeFile(final String potentialInput, final String MAGIC_HEADER_LINE) {
         try {
+            Path path = IOUtil.getPath(potentialInput);
             //isVCFStream closes the stream that's passed in
-            return isVCFStream(new FileInputStream(potentialInput), MAGIC_HEADER_LINE) ||
-                    isVCFStream(new GZIPInputStream(new FileInputStream(potentialInput)), MAGIC_HEADER_LINE) ||
-                    isVCFStream(new BlockCompressedInputStream(new FileInputStream(potentialInput)), MAGIC_HEADER_LINE);
+            return isVCFStream(Files.newInputStream(path), MAGIC_HEADER_LINE) ||
+                    isVCFStream(new GZIPInputStream(Files.newInputStream(path)), MAGIC_HEADER_LINE) ||
+                    isVCFStream(new BlockCompressedInputStream(Files.newInputStream(path)), MAGIC_HEADER_LINE);
         } catch ( FileNotFoundException e ) {
             return false;
         } catch ( IOException e ) {
diff --git a/src/test/java/htsjdk/tribble/util/ParsingUtilsTest.java b/src/test/java/htsjdk/tribble/util/ParsingUtilsTest.java
index 1c3ad1f54..85f414e87 100644
--- a/src/test/java/htsjdk/tribble/util/ParsingUtilsTest.java
+++ b/src/test/java/htsjdk/tribble/util/ParsingUtilsTest.java
@@ -1,6 +1,16 @@
 package htsjdk.tribble.util;
 
 
+import com.google.common.jimfs.Configuration;
+import com.google.common.jimfs.Jimfs;
+import htsjdk.samtools.util.IOUtil;
+import java.io.BufferedWriter;
+import java.io.File;
+import java.io.OutputStream;
+import java.io.OutputStreamWriter;
+import java.nio.file.FileSystem;
+import java.nio.file.Files;
+import java.nio.file.Path;
 import org.testng.Assert;
 import org.testng.annotations.Test;
 
@@ -118,6 +128,37 @@ public void testSplitJoinEmptyFirst() {
     }
 
     @Test
+    public void testFileDoesExist() throws IOException{
+        File tempFile = File.createTempFile(getClass().getSimpleName(), ".tmp");
+        tempFile.deleteOnExit();
+        tstExists(tempFile.getAbsolutePath(), true);
+        tstExists(tempFile.toURI().toString(), true);
+    }
+
+    @Test
+    public void testFileDoesNotExist() throws IOException{
+        File tempFile = File.createTempFile(getClass().getSimpleName(), ".tmp");
+        tempFile.delete();
+        tstExists(tempFile.getAbsolutePath(), false);
+        tstExists(tempFile.toURI().toString(), false);
+    }
+
+    @Test
+    public void testInMemoryNioFileDoesExist() throws IOException{
+        FileSystem fs = Jimfs.newFileSystem(Configuration.unix());
+        Path file = fs.getPath("/file");
+        Files.createFile(file);
+        tstExists(file.toUri().toString(), true);
+    }
+
+    @Test
+    public void testInMemoryNioFileDoesNotExist() throws IOException{
+        FileSystem fs = Jimfs.newFileSystem(Configuration.unix());
+        Path file = fs.getPath("/file");
+        tstExists(file.toUri().toString(), false);
+    }
+
+    @Test
     public void testFTPDoesExist() throws IOException{
         tstExists(AVAILABLE_FTP_URL, true);
     }
@@ -143,6 +184,26 @@ private void tstExists(String path, boolean expectExists) throws IOException{
     }
 
     @Test
+    public void testFileOpenInputStream() throws IOException{
+        File tempFile = File.createTempFile(getClass().getSimpleName(), ".tmp");
+        tempFile.deleteOnExit();
+        OutputStream os = IOUtil.openFileForWriting(tempFile);
+        BufferedWriter writer = new BufferedWriter(new OutputStreamWriter(os));
+        writer.write("hello");
+        writer.close();
+        tstStream(tempFile.getAbsolutePath());
+        tstStream(tempFile.toURI().toString());
+    }
+
+    @Test
+    public void testInMemoryNioFileOpenInputStream() throws IOException{
+        FileSystem fs = Jimfs.newFileSystem(Configuration.unix());
+        Path file = fs.getPath("/file");
+        Files.write(file, "hello".getBytes("UTF-8"));
+        tstStream(file.toUri().toString());
+    }
+
+    @Test
     public void testFTPOpenInputStream() throws IOException{
         tstStream(AVAILABLE_FTP_URL);
     }